Risk Factors and Development of a Predictive Nomogram Model for Acute Postoperative Pain in Oral Cancer

Risk Factors and Development of a Predictive Nomogram Model for Acute Postoperative Pain in Oral Cancer | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Risk Factors and Development of a Predictive Nomogram Model for Acute Postoperative Pain in Oral Cancer Fang Qi, Yiqun Kang, Long Zuo, LiangYu Chen, Yuan Yu, Tuo Ji, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7471981/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 04 Feb, 2026 Read the published version in BMC Oral Health → Version 1 posted 14 You are reading this latest preprint version Abstract This study aimed to determine the incidence and independent risk factors of acute postoperative pain in oral cancer patients and develop an individualized predictive nomogram. A retrospective cohort study included 458 oral cancer patients who underwent tumor resection with free flap reconstruction at Wuhan University’s Hospital of Stomatology (January 2023–December 2024). Demographics, medical history, tumor features, surgical variables, and preoperative anxiety/depression were collected. Pain intensity was assessed using the Numerical Rating Scale (NRS) on postoperative days 1, 2, 3, and 7. Independent risk factors were identified via multivariate analysis, and a nomogram was validated using ROC curves, calibration curves, and Decision Curve Analysis (DCA). The incidence of acute pain on postoperative day 3 was 74.67% (342/458), with 51.5% experiencing moderate pain (NRS 4–6) and 17.2% severe pain (NRS ≥ 7). Independent risk factors included education ≤ junior high school (OR = 0.29), no history of immunotherapy (OR = 0.12), larger tumor volume (OR = 20.53), unilateral (OR = 3.46) or bilateral lymph node dissection (OR = 10.95), free flap type (OR = 10.17), and preoperative anxiety/depression (OR = 2.71; all P 0.05) and significant clinical net benefits (DCA). In conclusion, acute postoperative pain in oral cancer is common and multifactorial. The nomogram accurately predicts this risk, aiding individualized analgesia and optimizing pain management. pain prediction risk stratification individualized analgesia perioperative pain management nomogram validation Figures Figure 1 Figure 2 Figure 3 Figure 4 Background Oral cancer, a prevalent head and neck malignancy, is witnessing a rising global incidence. According to the World Health Organization’s International Agency for Research on Cancer (2022), it accounts for approximately 417,000 new cases and 217,000 deaths annually worldwide, with over 60% of the global burden concentrated in Asia[1]. Surgical resection, the cornerstone of curative treatment, often involves complex tissue removal and reconstruction; postoperative pain impairs swallowing, speech, and social function, and correlates closely with complications, rehabilitation trajectories, and long-term quality of life [2]. However, critical gaps persist in research on acute postoperative pain in oral cancer, particularly regarding multicenter data integration, stratified analysis of influencing factors, and optimization of individualized analgesic strategies—all requiring urgent advancement. The intricate orofacial anatomy (encompassing trigeminal branches, salivary glands, and masticatory muscles) renders surgical trauma associated with multidimensional pain: nociceptive (tissue injury), neuropathic (nerve damage), and inflammatory sensitization [3][4]. Clinically, 40–65% of oral cancer patients experience inadequately controlled acute postoperative pain, a rate significantly higher than for malignancies elsewhere [5]. Importantly, 15–30% of these patients may progress to chronic pain if acute pain is untreated, exacerbating functional and psychological burdens. A cohort study of 1,200 patients found that those with a Visual Analogue Scale (VAS) score > 4 within 7 days postoperatively had a 2.81-fold higher risk of chronic pain at 3 months (95% CI: 1.97–3.99)[6]. Despite postoperative pain management being central to Enhanced Recovery After Surgery (ERAS), oral cancer-specific research remains limited. First, reported acute pain incidence varies widely (20–70%) due to differences in assessment timing, surgical procedures, and tools [7][8]. Second, existing studies on influencing factors focus primarily on single variables, lacking integrated multivariate analysis or predictive models [9][10][11]. Third, analgesic strategies rely on empirical regimens (e.g., NSAIDs with opioids), with no consensus on prophylactic gabapentinoid timing/dosage for nerve damage, leading to adverse reactions or inadequate analgesia in ~ 20% of patients [4]. This study aims to systematically investigate acute postoperative pain incidence in oral cancer patients, clarify associated tumor clinical/histopathological characteristics, and identify risk factors (demographic, psychosocial, surgical/anesthesia-related). A nomogram model will be developed to predict acute pain risk, providing a tool for individualized analgesic planning to optimize pain management and improve prognosis. Methods This retrospective cohort study was conducted at the Hospital of Stomatology, Wuhan University, from January 2023 to December 2024. The protocol was reviewed and approved by the Ethics Committee of the Hospital of Stomatology, Wuhan University (Approval No.: [2023] Lun Shen Zi (B11) Hao). Due to the retrospective nature, written informed consent was waived, and all data were de-identified for privacy protection. The study complied with the STROBE protocol. Patient Eligibility Criteria Inclusion criteria: Adult patients (≥ 18 years) who underwent oral cancer surgery under general anesthesia (tumor resection combined with free flap reconstruction) at our institution between January 2023 and December 2024. Core surgical components: (1) Resection of oral subsite lesions (buccal mucosa, tongue, gingiva, etc.); (2) Cervical lymph node dissection; (3) Reconstruction with anterolateral thigh, forearm, iliac bone, or fibular free flaps (individualized by tumor location/severity). Exclusion criteria: (1) Chronic pain history; (2) Long-term preoperative use of analgesics or psychotropics; (3) Incomplete medical records; (4) Non-oral primary or metastatic malignancies; (5) Flap crisis requiring secondary surgical exploration; (6) Postoperative transfer due to severe systemic complications; (7) Prior oral cancer surgery with recurrence reoperation. Eligible patients were identified via the hospital’s electronic medical record system and surgical database. Data Collection Demographics extracted: Age, gender, BMI, education (≤ junior high/≥high school), smoking, alcohol consumption, betel nut chewing history.Medical history: Comorbidities (diabetes, hypertension, etc.), chemotherapy/immunotherapy history.Tumor characteristics: Size, primary oral subsite, TNM stage, pathological type, lymph node size.Surgical variables: Free flap type, lymph node dissection method, total operative duration. Anesthesia protocol: Standardized endotracheal intubation with mechanical ventilation and intravenous-inhalational anesthesia (opioids: alfentanil, sufentanil, remifentanil; anesthetics: sevoflurane, propofol; muscle relaxant: cisatracurium). Intraoperative monitoring included heart rate, blood pressure, SpO₂, central venous pressure, and invasive arterial pressure. Postoperative analgesia used a standardized PCA pump (hydromorphone 0.1 mg/kg + ketamine 0.1 mg/kg + sodium chloride 100 mL at 2 mL/h). Preoperative assessments: 14-item HADS (1 week preoperatively; HADS-A/HADS-D subscales, 0–3 scoring; total score ≥ 8 defined as anxiety/depression) and NRS pain score (24 h preoperatively; 0–10 scale).Pain evaluation: Trained nurses recorded resting NRS scores preoperatively (day before) and on POD1, POD2, POD3, POD7. Inadequate/breakthrough pain: NRS > 3; severe pain: NRS ≥ 7. Primary outcome: Development and validation of a nomogram to predict postoperative acute pain risk. Secondary outcomes: Incidence of postoperative acute pain and identification of independent risk factors. Statistical Analysis Statistical analyses were performed using SPSS v30.0. Data were presented as counts/percentages or mean ± SD. Group comparisons used t-test, Mann-Whitney U test, or chi-square test. Binary univariate and multivariate logistic regression evaluated risk factors. ROC curves assessed predictive value of continuous variables. Nomograms were constructed and evaluated using RStudio v2025.05.0 + 496. A two-tailed P < 0.05 was statistically significant. Results Screening Process of Study Participants A total of 650 medical records were initially retrieved, with 458 patients meeting inclusion criteria and completing the study after rigorous screening. The remaining 192 patients were excluded for the following reasons: 77 with a history of prior oral cancer resection, 34 with postoperative flap crisis requiring secondary surgical exploration, 26 transferred to other institutions due to severe systemic diseases, 39 with incomplete medical documentation, and 16 with chronic pain history or preoperative use of analgesics/psychotropic medications. The study flow can be found in Fig. 1 . Demographic, Clinical, Tumor, and Surgical Characteristics of the Study Cohort Demographic, Clinical, and Tumor-Surgical Characteristics of the Study Cohort The study cohort included 458 patients with a median age of 52 years (IQR: 42–61 years) and median body weight of 65 kg (IQR: 58–72.63 kg); 77.9% were male, and 54.2% had a high school or higher education. Preoperatively, 22.7% had betel nut exposure history, 54.15% received chemotherapy, and 29.69% underwent immunotherapy. Common comorbidities included hypertension (34.3%), diabetes mellitus (17.7%), cardiovascular diseases (24.2%), urinary system diseases (24.5%), thyroid diseases (18.8%), and respiratory diseases (25.8%), with 57.6% reporting significant pain. Regarding tumors, the most prevalent size was 2–4 cm, and 36.5% were at TNM stage Ⅳ; over half had preoperative lymphadenopathy, predominantly 3–6 cm in size. Squamous cell carcinoma (91.7%) was the main histopathological type, with primary sites mostly the tongue (49.34%), buccal mucosa (22.5%), and alveolar region (16.2%). Surgically, 24.0% underwent unilateral lymph node dissection, 47.2% bilateral dissection, and the rest no dissection. Free flaps primarily included anterolateral thigh (45.2%), forearm (36.24%), iliac bone (13.32%), and fibular (5.24%) flaps, with a median operative duration of 370 minutes (IQR: 309–435 minutes).Detailed characteristics are presented in Table 1 . Table 1 Summary of the demographic and diagnostic characteristics of the study population Study characteristics Category Descriptive statistic Age Years 52[42, 61] Weight Kg 65[58,72.63] Education level Higher education 248(54.2%) Sex Male 357(77.9%) Betel quid or areca nut chewing 104(22.7%) Hypertension 157(34.3%) Diabetes 81(17.7%) Diseases of the cardiovascular system 111(24.2%) Diseases of the urological system 112(24.5%) Thyroid disease 86(18.8%) Diseases of the respiratory system 118(25.8%) Preoperative anxiety and depression state 205(44.8%) History of chemotherapy 266(58.1%) History of immunotherapy 136(29.7%) Preoperative pain pain 264(57.6%) Lymph node size 0cm 178(38.9%) 6cm 8(1.7%) Size of tumor 4cm 102(22.3%) TNM classification Stage I 64(14.0%) Stage II 80(17.5%) Stage III 147(32.1%) Stage IV 167(36.5%) Type of Cancer Squamous cell carcinoma 420(91.7%) Location of primary disease Tongue 226(49.3%) Alveolar region 74(16.2%) Floor of the mouth 32(7.0%) Buccal mucosa 103(22.5%) Palate 16(3.5%) Retro molar trigone area 7(1.5%) ULND 110(24.0%) BLND 216(47.2%) Site of flap transplantation antebrachium 166(36.2%) Anterolateral femoral skin flap 207(45.2%) Fibular flap 24(5.2%) cutaneous iliac flap 61(13.3%) Surgery time minute 370[309,435] TNM Tumor Node Metastasis,ULND Unilateral lymph node dissection,BLND Bilateral lymph node dissection Time-Series Analysis of Pain Severity This study analyzed the dynamic evolution of pain severity across time points. Over half of the patients reported preoperative pain. In the early postoperative period (POD1–POD2), > 80% experienced no significant pain, with low rates of other pain levels, indicating effective initial pain control. On POD3, 342 patients (74.67%) developed significant pain, stratified as mild (27 patients, 5.9%), moderate (236 patients, 51.5%), and severe (79 patients, 17.2%). By POD7, 38.9% of patients had moderate to severe pain, reflecting the dynamic progression of postoperative pain over time. Detailed data are in Fig. 2 . Analysis of Factors Associated with Postoperative Acute Pain in Oral Cancer Patients The presence of pain was significantly correlated with educational level (p < 0.001), history of diabetes mellitus (p = 0.035), history of chemotherapy (p = 0.007), history of immunotherapy (p = 0.007), preoperative anxiety and depression (p < 0.001), and clinical lymph node involvement (p < 0.001). Further analysis indicated that the occurrence of postoperative acute pain was also significantly associated with tumor size (p < 0.001), TNM classification (p < 0.001), primary tumor site (p < 0.001), approach to cervical lymph node dissection (p < 0.001), and type of free flap (p < 0.001). Detailed characteristics are presented in Table 2 . Table 2 Demographic and clinical characteristics associated with acute postoperative pain in oral cancer patients Variables Acute Postoperative Pain p-value Yes(n = 342) No(n = 116) Age(years) 51.64[50.28, 53] 51.22[48.95,53.5] 0.725 Weight(kg) 65.93[64.66,67.21] 66.60[64.5,68.7] 0.493 Education level, n(%) - - < 0.001* =higher education 133(38.9%) 77(66.4%) Sex,n(%) - - 0.88 male 266(77.8%) 91(78.4%) female 76(22.2%) 25(21.6%) Betel quid or areca nut chewing,n(%) 82(24%) 22(19%) 0.266 Hypertension,n(%) 119(34.8%) 38(32.8%) 0.69 Diabetes,n(%) 53(15.5% 28(24.1) 0.035* Diseases of the cardiovascular system,n(%) 82(24%) 29(25%) 0.824 Diseases of the urological system,n(%) 84(24.6%) 28(24.1%) 0.927 Thyroid disease,n(%) 66(19.30%) 20(17.2%) 0.624 Diseases of the respiratory system,n(%) 90(26.3%) 28(24.1%) 0.643 Preoperative anxiety and depression state,n(%) 174(50.9%) 31(26.7%) < 0.001* History of chemotherapy,n(%) 211(61.7%) 55(47.4%) 0.007* History of immunotherapy,n(%) 90(26.3%) 46(39.7%) 0.007* Preoperative pain 205(59.9%) 59(50.9%) 0.087 Lymph node size,n(%) - - < 0.001* 0cm 113(33%) 65(56%) 6cm 7(2%) 1(0.9%) Size of tumor,n(%) - - < 0.001* 4cm 93(27.2%) 9(7.8%) TNM classification,n(%) - - < 0.001* Stage I 19(5.6%) 45(38.8%) Stage II 64(18.7%) 16(13.8%) Stage III 124(36.3%) 23(19.8%) Stage IV 135(39.5%) 32(27.6%) Type of Cancer,n(%) - - 0.072 Squamous cell carcinoma 309(90.4%) 111(95.7) Others 33(9.6%) 5(4.3%) Location of primary disease,n(%) - - < 0.001* Tongue 152(44.4%) 74(63.8%) Alveolar region 70(20.5%) 4(3.4%) Floor of the mouth 24(7.0%) 8(6.9%) Buccal mucosa 77(22.5%) 26(22.4%) Palate 13(3.8%) 3(2.6%) Retro molar trigone area 6(1.8%) 1(0.9%) ULND,n(%) 65(19%) 45(38.8%) < 0.001* BLND,n(%) 192(56.1%) 24(20.7%) < 0.001* Site of flap transplantation,n(%) - - < 0.001* antebrachium 98(28.7%) 68(58.6%) Anterolateral femoral skin flap,n(%) 166(48.5%) 41(35.3%) Fibular flap 21(6.1%) 3(2.6%) cutaneous iliac flap 57(16.7%) 4(3.4%) Surgery time(min) 371.65[360.46,382.84] 3449.66[329.04,370.27] 0.207 TNM Tumor Node Metastasis,ULND Unilateral lymph node dissection,BLND Bilateral lymph node dissection, *P-value < 0.05 by chi-square test, Fisher exact test, t-test, or Mann-Whitney U-test Multivariate Analysis of Independent Risk Factors for Postoperative Acute Pain in Oral Cancer Patients A total of 12 potential risk factors with p < 0.05 identified in Tables 2 were included in univariate and multivariate logistic regression analyses. Multivariate results identified the following independent risk factors for acute pain on postoperative day 3: lower educational level (OR = 0.29, 95% CI: 0.15–0.58, p < 0.001), no prior immunotherapy (OR = 0.12, 95% CI: 0.04–0.33, p < 0.001), larger tumor size (OR = 20.53, 95% CI: 6.9–61.12, p < 0.001), unilateral lymph node dissection (OR = 3.46, 95% CI: 1.29–9.26, p = 0.014), bilateral lymph node dissection (OR = 10.95, 95% CI: 3.25–36.97, p < 0.001), flap type (vs. forearm flap: anterolateral thigh flap, OR = 2.88, 95% CI: 1.43–5.79, p = 0.003; fibular flap, OR = 8.28, 95% CI: 1.53–44.91, p = 0.014; iliac bone flap, OR = 10.17, 95% CI: 2.52–41.00, p = 0.001), and preoperative anxiety/depression (OR = 2.71, 95% CI: 1.42–5.20, p = 0.003). (Table 3 ). Table 3 Univariate and multivariate logistic regression analysis of postoperative acute pain in patients undergoing oral and maxillofacial tumor surgery Variables Univariate Multivariate OR(95%CI) P-value OR(95%CI) P-value Education level 0.32[0.21, 0.5] < 0.001* 0.29[0.15,0.58] < 0.001* Diabetes 0.5[0.34,0.97] 0.036* 1.36[0.56,3.32] 0.497 History of chemotherapy 1.79[1.17,2.73] 0.007* - - History of immunotherapy 0.54[0.35,0.85] 0.007* 0.12[0.04,0.33] < 0.001* Adenophyma 2.58[1.68, 3.97] < 0.001* 0.93[0.16,5.48] 0.939 Size of tumor(vs 2cm 13.43[8.13,22.17] < 0.001* 20.53[6.9,61.12] < 0.001* TNM classification(vs Stage I) < 0.001* 0.932 Stage II 9.47[4.4,20.39] < 0.001* 1.475[0.298,7,288] 0.658 Stage III 12.77[6.36,25.63] < 0.001* - 0.983 Stage IV 9.99[5.16,19.34] < 0.001* - 0.983 Location of primary disease(tongue) 2.2[1.43,3.4] < 0.001* 1.27[0.63,2.56] 0.496 ULND 0.37[0.23,0.59]] < 0.001* 3.46[1.29,9.26] 0.014* BLND 4.91[2.98,8.07] < 0.001* 10.95[3.25,36.97] < 0.001* Site of flap transplantation(vs antebrachium) < 0.001* 0.039* Anterolateral femoral skin flap 2.81[1.77,4.45] < 0.001* 2.88[1.43,5.79] 0.003 Fibular flap 4.86[1.39,16.93] 0.013* 8.28[1.53,44.91] 0.014 Cutaneous iliac flap 9.89[3.43,28.54] < 0.001* 10.17[2.52,41.00] 0.001 Preoperative anxiety and depression state 2.84[1.79,4.51] < 0.001* 2.71[1.42,5.20] 0.003* TNM Tumor Node Metastasis,ULND Unilateral lymph node dissection,BLND Bilateral lymph node dissection, OR odds ratio, CI confdence interval. *P-value < 0.05 Construction of a Predictive Model for Postoperative Acute Pain in Oral Cancer Patients A nomogram model was developed to individually predict postoperative day 3 acute pain risk in oral cancer patients, incorporating independent risk factors identified via multivariate analysis: educational level, immunotherapy history, tumor size, lymph node dissection approach, flap type, and preoperative anxiety/depression (Fig. 3 A). Receiver operating characteristic (ROC) curve analysis evaluated the model’s discriminative performance, revealing a prediction cutoff value of 0.79 (sensitivity = 0.87; specificity = 0.86). The area under the curve (AUC) was 0.923 (95% CI: 0.895–0.951), indicating excellent ability to distinguish between patients with and without postoperative acute pain. The narrow 95% CI confirmed result stability and reliability. (Fig. 3 B). Validation of the Nomogram Model for Predicting Postoperative Acute Pain in Oral Cancer Patients To verify the model’s stability and generalizability, internal (training set, n = 320) and external (validation set, n = 138) validations were performed via R software. ROC curve analysis showed the training set yielded an AUC of 0.928 (95% CI: 0.898–0.958; Fig. 4 A) and the validation set an AUC of 0.911 (95% CI: 0.849–0.973; Fig. 4 B), demonstrating the model stably stratified postoperative acute pain risk across datasets with superior discriminative efficacy, and its AUC improved by > 0.2 vs. single-indicator prediction. Calibration curves (Figs. 4 C, 4 D) assessed by the Hosmer-Lemeshow test confirmed consistency with the ideal model in both sets (training set: P = 0.885; validation set: P = 0.804; both P > 0.05), validating predictive accuracy and stable calibration. DCA (Figs. 4 E, 4 F) showed the nomogram outperformed “no model” and “AI-only” strategies across sets; at high-risk thresholds (0.1–0.9), its net benefit curve was higher, and within 0.3–0.7 (critical for decisions), it identified 8–12 more true pain cases per 100 patients while avoiding 5–7 over-analgesia instances. Subgroup analyses by tumor sites (tongue, buccal, gingival) showed the tongue subgroup’s AUC of 0.902 (95% CI: 0.800–1; P = 0.534 vs. overall) confirmed generalizability, and age-stratified analysis found the elderly subgroup (> 60 years) had an AUC of 0.996 (95% CI: 0.986–1) with no age-related difference (P = 0.332), demonstrating stability. Thus, the nomogram exhibits excellent discriminative ability, accuracy, and clinical utility, validated across datasets and subgroups to guide individualized analgesic regimens and optimize perioperative outcomes for oral cancer patients. Discussion This retrospective analysis of 458 oral cancer patients undergoing free flap reconstruction represents the first systematic investigation to delineate the prevalence of postoperative acute pain, identify multidimensional independent risk factors, and develop a nomogram model with robust predictive performance (AUC = 0.923). These findings offer novel insights into the pathophysiological mechanisms of postoperative pain in oral cancer and establish a foundation for individualized pain management strategies. The observed 74.6% prevalence of postoperative pain aligns with broader head and neck malignancy epidemiological data: Khawaja et al. documented that up to 70% of such patients experience pain[12], while Imani et al.emphasized that surgery and radiotherapy frequently induce acute and chronic discomfort[13]. The marginally higher rate in oral cancer may stem from dual orofacial surgical trauma and flap donor-site injury, compounded by the oral cavity’s dense trigeminal innervation (3–5-fold higher nerve density in tongue/gingiva than trunk skin)[7]. Surgical trauma damages nerve fibers and activates TRPV1/P2X3 receptors[14], inducing primary afferent sensitization, while postoperative functional activities (swallowing, speech) perpetuate mechanical stimulation, amplifying pain distinct from non-oral malignancies[15]. Patients received standardized patient-controlled intravenous analgesia (PCIA: hydromorphone 0.1 mg/kg + ketamine 0.1 mg/kg + 0.9% sodium chloride 100 mL at 2 mL/h) for 48 postoperative hours, with marked efficacy: pain incidence was 16.8% (median NRS 0, IQR 0–2) on day 1 and 19.7% (median NRS 0, IQR 0–2) on day 2. Due to logistical and cost constraints, PCIA was not continued beyond 48 hours, contributing to a sharp escalation in pain incidence to 74.6% on day 3. This corroborates Orgill et al.’s finding that "only 35% of head and neck cancer patients achieve adequate pain control," [16]underscoring a critical management challenge. Among patients with NRS ≥ 1 on day 3, only a subset required NSAID intervention, while others declined medication. Given potential bias from variable medication utilization, later NRS scores (e.g., day 7) were excluded from incidence analyses. Tumor size emerged as a prominent independent risk factor. Larger tumors involve broader infiltration, heightened metastatic potential, and extensive invasion of adjacent tissues, nerves, and bone. Resection induces greater iatrogenic damage, with postoperative inflammatory responses (e.g., 3–5-fold elevations in IL-6 and TNF-α) correlating positively with tumor diameter[17]. TNM staging analyses revealed stepwise pain incidence increases (stage I: 14.0% vs. stage IV: 36.5%), validating tumor burden’s impact. Surgical approach strongly associates with pain via resection extent, tissue trauma, and nerve exposure risk. Patients undergoing bilateral cervical lymph node dissection faced higher pain risk (OR = 10.95) than unilateral dissection (OR = 3.46), attributable to bilateral spinal accessory nerve and cervical plexus (C2–C4) injury: spinal accessory damage induces trapezius denervation and shoulder pain, while cervical plexus injury causes anterior neck dysesthesia. Nerve regeneration in levator scapulae is 40% slower after bilateral dissection, prolonging pain[1]. Flap type analyses showed iliac bone flaps conferred higher risk (OR = 10.17) than other free flaps, reflecting greater donor-site trauma (93% pain incidence vs. 59% with forearm flaps)[18]. Iliac flap harvest transects gluteus maximus attachments and superior gluteal nerve deep branches, with osseous resection inducing more intense pain than soft-tissue dissection. Preoperative anxiety and depression reinforce the "psycho-neuro-immune axis" in pain modulation[19]. They upregulate hypothalamic-pituitary-adrenal axis activity, elevating cortisol and lowering pain thresholds, while promoting inflammatory mediator release (CRP, IL-1β) to perpetuate a "pain-anxiety" loop [20],[21]. Patients with abnormal preoperative HADS scores had nearly 3-fold increased pain risk, highlighting preoperative psychological intervention as a potential adjunct. Educational level associations likely reflect health literacy disparities: patients with ≤ junior high education demonstrated poorer comprehension of pain assessment tools and communication with providers, potentially delaying intervention[22]. This subgroup’s higher pain incidence may also relate to delayed presentation (larger surgical defects), economic constraints, and inadequate insurance, leading to passive pain tolerance. Higher-educated patients may better utilize cognitive-behavioral strategies for pain management[23][24]. Notably, immunotherapy history emerged as a protective factor. Immune checkpoint inhibitors may modulate pain via neuro-immune crosstalk, suppressing macrophage secretion of nerve injury factors (e.g., NGF) and enhancing T-cell-mediated clearance of damaged nerves, mitigating neuropathic pain[25][26]. The gut microbiome-immune axis also influences pain through immunomodulation[27], while adequate pain control can reverse immunosuppression, improving immune status. However, limited sample size necessitates multicenter studies to clarify pathways and long-term effects. This study’s innovations are threefold: first, granular pain risk stratification across demographic, tumor-related, surgical, and psychological domains. Second, advanced multivariate predictive modeling via a nomogram (AUC = 0.923) enabling "preoperative-intraoperative-postoperative" risk prediction, aligned with ERAS "preventive analgesia." Third, identification of a critical gap: 48-hour PCA insufficiently controls complex pain (51.5% moderate, 17.2% severe on day 3), necessitating optimized multimodal analgesia and extended duration. Limitations include retrospective bias with unrecorded variables (e.g., intraoperative opioids, infections). Pain assessment was restricted to 7 days, lacking chronic pain evaluation; prospective studies are needed for long-term outcomes. Mechanistic insights are limited by absent biomarker analyses (e.g., COMT polymorphisms, cytokines). Single-center data may reflect regional practices, requiring multicenter validation. Future research should prioritize replication and mechanistic investigations. Conclusion This study confirms high prevalence and multifactorial etiology of acute postoperative pain in oral cancer. The nomogram provides a robust tool for risk stratification and individualized management. Future research will refine precision pain prevention through mechanistic studies and translational validation. Abbreviations NRS Numerical rating scale DCA Decision curve analysis OR Odds ratio AUC Area under the curve‌ ERAS Enhanced recovery after surgery NSAIDs Non-steroidal anti-inflammatory drugs POD Postoperation day TNM Tumor node metastasis ULND Unilateral lymph node dissection BLND Bilateral lymph node dissection CRP cAMP receptor protein HADS Hospital anxiety and depression scale NGF Nerve growth factor PCA Patient-controlled analgesia Declarations Data availability All data generated or analyzed during this study are included in this published article. Acknowledgments This study is a retrospective analysis of medical record data. No external funding was received during the research design, data collection, analysis, or manuscript preparation process. There was no specific institutional or departmental funding support for this study. Funding This study received no funding. Ethics declarations Ethics approval and consent to participate The study was reviewed and approved by the Ethics Committee of the Hospital of Stomatology, Wuhan University (Approval number:[2023] Lun Shen Zi (B11))on April 12, 2023.All patients enrolled for the study signed an informed consent. Consent for publication Not applicable. Competing interests The authors declare no competing interests. Author Contributions Fang Qi: contributed to the design, and acquisition, analysis, and interpretation of data; drafted the manuscript and critically revised manuscript. Yiqun Kang: contributed to the design and acquisition of data, critically revised manuscript.. Long Zuo: contributed to acquisition and interpretation of data, critically revised manuscript. LiangYu Chen: contributed to conception and acquisition of data, critically revised manuscript. Yuan Yu: contributed to conception and acquisition of datacritically revised manuscript. Tuo Ji: contributed to conception and acquisition of data, critically revised manuscript.Wei Peng: contributed to interpretation of data, critically revised manuscript. Tiejun Zhan: Contributed to interpretation of data, critically revised manuscript. Li Wang: contributed to conception and design, and acquisition, analysis, and interpretation of data; drafted the manuscript and critically revised it for important intellectual content. All authors gave final approval and agreed to be accountable for all aspects of work ensuring integrity and accuracy. Conflict of Interest Statement All authors declare that there are no financial conflicts of interest, personal conflicts of interest, or other potential conflicts of interest related to the subject of this study in the process of conducting the research and publishing this manuscript. 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Chen D, Yang H, Yang L, Tang Y, Zeng H, He J, Chen W, Qu Y, Hu Y, Xu Y et al: Preoperative psychological symptoms and chronic postsurgical pain: analysis of the prospective China Surgery and Anaesthesia Cohort study. Br J Anaesth 2024, 132(2):359-371. Ing JW: Head and Neck Cancer Pain. Otolaryngol Clin North Am 2017, 50(4):793-806. Hinther A, Nakoneshny SC, Chandarana SP, Wayne Matthews T, Dort JC: Efficacy of postoperative pain management in head and neck cancer patients. J Otolaryngol Head Neck Surg 2018, 47(1):29. Hoofwijk DMN, van Reij RRI, Rutten BPF, Kenis G, Theunissen M, Joosten EA, Buhre WF, van den Hoogen NJ: Genetic polymorphisms and prediction of chronic post-surgical pain after hysterectomy-a subgroup analysis of a multicenter cohort study. Acta Anaesthesiol Scand 2019, 63(8):1063-1073. Mi X, Zou B, Rashidi P, Baharloo R, Fillingim RB, Wallace MR, Crispen PL, Parvataneni HK, Prieto HA, Gray CF et al: Effects of Patient and Surgery Characteristics on Persistent Postoperative Pain: A Mediation Analysis. Clin J Pain 2021, 37(11):803-811. Armstrong RA, Fayaz A, Manning GLP, Moonesinghe SR, Peri-operative Quality Improvement Programme delivery t, Oliver CM, collaborative P: Predicting severe pain after major surgery: a secondary analysis of the Peri-operative Quality Improvement Programme (PQIP) dataset. Anaesthesia 2023, 78(7):840-852. Imani F, Mohebbi S, Mohseni M, Karimi B, Rahimi S, Dikafraz Shokooh GA: A Narrative Review on Pain Management in Head and Neck Cancer: Integrating Multimodal Analgesia and Interventional Procedures. Anesth Pain Med 2024, 14(3):e146825. Zhong W, Ma X, Xing Y, Kim DK, Wang A, Jiang W, Xu T: Blockade of peripheral nociceptive signal input relieves the formation of spinal central sensitization and retains morphine efficacy in a neuropathic pain rat model. Neurosci Lett 2020, 716:134643. Ye Y, Jensen DD, Viet CT, Pan HL, Campana WM, Amit M, Boada MD: Advances in Head and Neck Cancer Pain. J Dent Res 2022, 101(9):1025-1033. Orgill R, Krempl GA, Medina JE: Acute pain management following laryngectomy. Arch Otolaryngol Head Neck Surg 2002, 128(7):829-832. Khawaja SN, Jamshed A, Hussain RT: Prevalence of pain in oral cancer: A retrospective study. Oral Dis 2021, 27(7):1806-1812. Ekstein MP, Weinbroum AA: Immediate postoperative pain in orthopedic patients is more intense and requires more analgesia than in post-laparotomy patients. Pain Med 2011, 12(2):308-313. Yang MMH, Hartley RL, Leung AA, Ronksley PE, Jette N, Casha S, Riva-Cambrin J: Preoperative predictors of poor acute postoperative pain control: a systematic review and meta-analysis. BMJ Open 2019, 9(4):e025091. Franqueiro AR, Wilson JM, He J, Azizoddin DR, Karamnov S, Rathmell JP, Soens M, Schreiber KL: Prospective Study of Preoperative Negative Affect and Postoperative Pain in Patients Undergoing Thoracic Surgery: The Moderating Role of Sex. J Clin Med 2024, 13(19). Niklasson A, Finan PH, Smith MT, Forsberg A, Dietz N, Kander T, Werner MU, Irwin MR, Kosek E, Bjurstrom MF: The relationship between preoperative sleep disturbance and acute postoperative pain control: A systematic review and meta-analysis. Sleep Med Rev 2025, 79:102014. van Lankveld W, Afram B, Staal JB, van der Sande R: The IASP pain curriculum for undergraduate allied health professionals: educators defining competence level using Dublin descriptors. BMC Med Educ 2020, 20(1):60. Wideman TH, Miller J, Bostick G, Thomas A, Bussieres A, Wickens RH: The current state of pain education within Canadian physiotherapy programs: a national survey of pain educators. Disabil Rehabil 2020, 42(9):1332-1338. Zhang C, Li Y, Yu Y, Li Z, Xu X, Talifu Z, Liu W, Yang D, Gao F, Wei S et al: Impact of inflammation and Treg cell regulation on neuropathic pain in spinal cord injury: mechanisms and therapeutic prospects. Front Immunol 2024, 15:1334828. Ho MFS, Farkas O, Faria AV, Plemel JR, Kerr BJ: A recent history of immune cell sex differences in the peripheral nervous system in persistent pain states. Brain Behav Immun 2025, 128:766-775. Santoni M, Miccini F, Battelli N: Gut microbiota, immunity and pain. Immunol Lett 2021, 229:44-47. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 04 Feb, 2026 Read the published version in BMC Oral Health → Version 1 posted Editorial decision: Revision requested 19 Dec, 2025 Reviews received at journal 16 Dec, 2025 Reviewers agreed at journal 16 Dec, 2025 Reviews received at journal 25 Nov, 2025 Reviews received at journal 19 Nov, 2025 Reviewers agreed at journal 17 Nov, 2025 Reviewers agreed at journal 14 Nov, 2025 Reviews received at journal 06 Nov, 2025 Reviewers agreed at journal 06 Nov, 2025 Reviewers invited by journal 24 Sep, 2025 Editor invited by journal 12 Sep, 2025 Editor assigned by journal 08 Sep, 2025 Submission checks completed at journal 08 Sep, 2025 First submitted to journal 27 Aug, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7471981","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":524784106,"identity":"e06b495d-17e9-4253-a885-80eb29358b4e","order_by":0,"name":"Fang Qi","email":"","orcid":"","institution":"Wuhan University","correspondingAuthor":false,"prefix":"","firstName":"Fang","middleName":"","lastName":"Qi","suffix":""},{"id":524784108,"identity":"a1fc5a2f-2fca-403c-b212-bd5ce62b9015","order_by":1,"name":"Yiqun Kang","email":"","orcid":"","institution":"Wuhan 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07:25:25","extension":"xml","order_by":11,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":91481,"visible":true,"origin":"","legend":"","description":"","filename":"d42c43c7393a4a5e95add2769bbb84771structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7471981/v1/799940b5eeae01055524e6eb.xml"},{"id":93013931,"identity":"767a9ea7-f82e-421e-a537-6ad0e5102c77","added_by":"auto","created_at":"2025-10-08 07:33:25","extension":"html","order_by":12,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":100470,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7471981/v1/2c909417e9b2621bb69f81eb.html"},{"id":93013425,"identity":"3e8a8e4d-5373-4b61-9064-4c6b2ab610c5","added_by":"auto","created_at":"2025-10-08 07:25:25","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":129695,"visible":true,"origin":"","legend":"\u003cp\u003eDevelopment of a Nomogram Model to Predict the Risk of Postoperative pain in oral and maxillofacial tumors Surgery Patients\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7471981/v1/79025f3e71af80933228050d.png"},{"id":93013426,"identity":"8f3a9a6c-7745-4956-a0d7-c35e3a3a3fcb","added_by":"auto","created_at":"2025-10-08 07:25:25","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":65227,"visible":true,"origin":"","legend":"\u003cp\u003ePain severity at different time points(A).The degree of pain on the third day after the operation(B).\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7471981/v1/909666e8e5381588084f4a75.png"},{"id":93013925,"identity":"a9b4f273-402a-440c-97be-26d1a1458256","added_by":"auto","created_at":"2025-10-08 07:33:25","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":132372,"visible":true,"origin":"","legend":"\u003cp\u003eNomogram model (A), ROC curve (B) and calibration curve (C) of acute pain after oral and maxillofacial tumor. edu: education, immunT: history of immunotherapy, ULND: unilateral lymph node dissection, BLND: BiLateral lymph node dissection, surgtype: flap surgery type, depressed:preoperative anxiety and depression state.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-7471981/v1/781db8500cef954db6c4af37.png"},{"id":93013428,"identity":"c416377d-3c8d-4a4a-b1dd-a625ca81c4b0","added_by":"auto","created_at":"2025-10-08 07:25:25","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":175726,"visible":true,"origin":"","legend":"\u003cp\u003eROC curve analysis was performed to evaluate the nomogram model of postoperative acute pain in oral and maxillofacial tumors in the training set (A) and validation set (B);Nomogram model evaluation of postoperative acute pain of oral and maxillofacial tumors in the training set (C) and validation set (D) based on calibration curve analysis;Nomogram model evaluation of postoperative acute pain of oral and maxillofacial tumors in the training set (E) and validation set (F) by DCA curve analysis.ROC,Receiver operating characteristic curve;AUC,Area under the curve;DCA, Decision Curve Analysis.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-7471981/v1/fa98b2de832f85580a299c13.png"},{"id":102234053,"identity":"88d171ff-cd5b-4dd0-ada8-e9b20f3c11dd","added_by":"auto","created_at":"2026-02-09 16:05:25","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1506577,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7471981/v1/7cb52f35-ed9d-4407-9b8f-2ebca7271932.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Risk Factors and Development of a Predictive Nomogram Model for Acute Postoperative Pain in Oral Cancer","fulltext":[{"header":"Background","content":"\u003cp\u003eOral cancer, a prevalent head and neck malignancy, is witnessing a rising global incidence. According to the World Health Organization\u0026rsquo;s International Agency for Research on Cancer (2022), it accounts for approximately 417,000 new cases and 217,000 deaths annually worldwide, with over 60% of the global burden concentrated in Asia[1]. Surgical resection, the cornerstone of curative treatment, often involves complex tissue removal and reconstruction; postoperative pain impairs swallowing, speech, and social function, and correlates closely with complications, rehabilitation trajectories, and long-term quality of life [2]. However, critical gaps persist in research on acute postoperative pain in oral cancer, particularly regarding multicenter data integration, stratified analysis of influencing factors, and optimization of individualized analgesic strategies\u0026mdash;all requiring urgent advancement.\u003c/p\u003e\u003cp\u003eThe intricate orofacial anatomy (encompassing trigeminal branches, salivary glands, and masticatory muscles) renders surgical trauma associated with multidimensional pain: nociceptive (tissue injury), neuropathic (nerve damage), and inflammatory sensitization [3][4]. Clinically, 40\u0026ndash;65% of oral cancer patients experience inadequately controlled acute postoperative pain, a rate significantly higher than for malignancies elsewhere [5]. Importantly, 15\u0026ndash;30% of these patients may progress to chronic pain if acute pain is untreated, exacerbating functional and psychological burdens. A cohort study of 1,200 patients found that those with a Visual Analogue Scale (VAS) score\u0026thinsp;\u0026gt;\u0026thinsp;4 within 7 days postoperatively had a 2.81-fold higher risk of chronic pain at 3 months (95% CI: 1.97\u0026ndash;3.99)[6]. Despite postoperative pain management being central to Enhanced Recovery After Surgery (ERAS), oral cancer-specific research remains limited. First, reported acute pain incidence varies widely (20\u0026ndash;70%) due to differences in assessment timing, surgical procedures, and tools [7][8]. Second, existing studies on influencing factors focus primarily on single variables, lacking integrated multivariate analysis or predictive models [9][10][11]. Third, analgesic strategies rely on empirical regimens (e.g., NSAIDs with opioids), with no consensus on prophylactic gabapentinoid timing/dosage for nerve damage, leading to adverse reactions or inadequate analgesia in ~\u0026thinsp;20% of patients [4].\u003c/p\u003e\u003cp\u003eThis study aims to systematically investigate acute postoperative pain incidence in oral cancer patients, clarify associated tumor clinical/histopathological characteristics, and identify risk factors (demographic, psychosocial, surgical/anesthesia-related). A nomogram model will be developed to predict acute pain risk, providing a tool for individualized analgesic planning to optimize pain management and improve prognosis.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis retrospective cohort study was conducted at the Hospital of Stomatology, Wuhan University, from January 2023 to December 2024. The protocol was reviewed and approved by the Ethics Committee of the Hospital of Stomatology, Wuhan University (Approval No.: [2023] Lun Shen Zi (B11) Hao). Due to the retrospective nature, written informed consent was waived, and all data were de-identified for privacy protection. The study complied with the STROBE protocol.\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003ePatient Eligibility Criteria\u003c/h2\u003e\u003cp\u003eInclusion criteria: Adult patients (\u0026ge;\u0026thinsp;18 years) who underwent oral cancer surgery under general anesthesia (tumor resection combined with free flap reconstruction) at our institution between January 2023 and December 2024. Core surgical components: (1) Resection of oral subsite lesions (buccal mucosa, tongue, gingiva, etc.); (2) Cervical lymph node dissection; (3) Reconstruction with anterolateral thigh, forearm, iliac bone, or fibular free flaps (individualized by tumor location/severity).\u003c/p\u003e\u003cp\u003eExclusion criteria: (1) Chronic pain history; (2) Long-term preoperative use of analgesics or psychotropics; (3) Incomplete medical records; (4) Non-oral primary or metastatic malignancies; (5) Flap crisis requiring secondary surgical exploration; (6) Postoperative transfer due to severe systemic complications; (7) Prior oral cancer surgery with recurrence reoperation. Eligible patients were identified via the hospital\u0026rsquo;s electronic medical record system and surgical database.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eData Collection\u003c/h3\u003e\n\u003cp\u003eDemographics extracted: Age, gender, BMI, education (\u0026le;\u0026thinsp;junior high/\u0026ge;high school), smoking, alcohol consumption, betel nut chewing history.Medical history: Comorbidities (diabetes, hypertension, etc.), chemotherapy/immunotherapy history.Tumor characteristics: Size, primary oral subsite, TNM stage, pathological type, lymph node size.Surgical variables: Free flap type, lymph node dissection method, total operative duration.\u003c/p\u003e\u003cp\u003eAnesthesia protocol: Standardized endotracheal intubation with mechanical ventilation and intravenous-inhalational anesthesia (opioids: alfentanil, sufentanil, remifentanil; anesthetics: sevoflurane, propofol; muscle relaxant: cisatracurium). Intraoperative monitoring included heart rate, blood pressure, SpO₂, central venous pressure, and invasive arterial pressure. Postoperative analgesia used a standardized PCA pump (hydromorphone 0.1 mg/kg\u0026thinsp;+\u0026thinsp;ketamine 0.1 mg/kg\u0026thinsp;+\u0026thinsp;sodium chloride 100 mL at 2 mL/h).\u003c/p\u003e\u003cp\u003ePreoperative assessments: 14-item HADS (1 week preoperatively; HADS-A/HADS-D subscales, 0\u0026ndash;3 scoring; total score\u0026thinsp;\u0026ge;\u0026thinsp;8 defined as anxiety/depression) and NRS pain score (24 h preoperatively; 0\u0026ndash;10 scale).Pain evaluation: Trained nurses recorded resting NRS scores preoperatively (day before) and on POD1, POD2, POD3, POD7. Inadequate/breakthrough pain: NRS\u0026thinsp;\u0026gt;\u0026thinsp;3; severe pain: NRS\u0026thinsp;\u0026ge;\u0026thinsp;7.\u003c/p\u003e\u003cp\u003ePrimary outcome: Development and validation of a nomogram to predict postoperative acute pain risk. Secondary outcomes: Incidence of postoperative acute pain and identification of independent risk factors.\u003c/p\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003eStatistical analyses were performed using SPSS v30.0. Data were presented as counts/percentages or mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD. Group comparisons used t-test, Mann-Whitney U test, or chi-square test. Binary univariate and multivariate logistic regression evaluated risk factors. ROC curves assessed predictive value of continuous variables. Nomograms were constructed and evaluated using RStudio v2025.05.0\u0026thinsp;+\u0026thinsp;496. A two-tailed P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was statistically significant.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003eScreening Process of Study Participants\u003c/h2\u003e\u003cp\u003e A total of 650 medical records were initially retrieved, with 458 patients meeting inclusion criteria and completing the study after rigorous screening. The remaining 192 patients were excluded for the following reasons: 77 with a history of prior oral cancer resection, 34 with postoperative flap crisis requiring secondary surgical exploration, 26 transferred to other institutions due to severe systemic diseases, 39 with incomplete medical documentation, and 16 with chronic pain history or preoperative use of analgesics/psychotropic medications. The study flow can be found in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eDemographic, Clinical, Tumor, and Surgical Characteristics of the Study Cohort\u003c/h2\u003e\u003cp\u003eDemographic, Clinical, and Tumor-Surgical Characteristics of the Study Cohort The study cohort included 458 patients with a median age of 52 years (IQR: 42\u0026ndash;61 years) and median body weight of 65 kg (IQR: 58\u0026ndash;72.63 kg); 77.9% were male, and 54.2% had a high school or higher education. Preoperatively, 22.7% had betel nut exposure history, 54.15% received chemotherapy, and 29.69% underwent immunotherapy. Common comorbidities included hypertension (34.3%), diabetes mellitus (17.7%), cardiovascular diseases (24.2%), urinary system diseases (24.5%), thyroid diseases (18.8%), and respiratory diseases (25.8%), with 57.6% reporting significant pain. Regarding tumors, the most prevalent size was 2\u0026ndash;4 cm, and 36.5% were at TNM stage Ⅳ; over half had preoperative lymphadenopathy, predominantly 3\u0026ndash;6 cm in size. Squamous cell carcinoma (91.7%) was the main histopathological type, with primary sites mostly the tongue (49.34%), buccal mucosa (22.5%), and alveolar region (16.2%). Surgically, 24.0% underwent unilateral lymph node dissection, 47.2% bilateral dissection, and the rest no dissection. Free flaps primarily included anterolateral thigh (45.2%), forearm (36.24%), iliac bone (13.32%), and fibular (5.24%) flaps, with a median operative duration of 370 minutes (IQR: 309\u0026ndash;435 minutes).Detailed characteristics are presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eSummary of the demographic and diagnostic characteristics of the study population\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStudy\u0026nbsp;characteristics\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCategory\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eDescriptive\u0026nbsp;statistic\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eYears\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e52[42, 61]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWeight\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eKg\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e65[58,72.63]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEducation\u0026nbsp;level\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHigher\u0026nbsp;education\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e248(54.2%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e357(77.9%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBetel\u0026nbsp;quid\u0026nbsp;or\u0026nbsp;\u003c/p\u003e\u003cp\u003eareca\u0026nbsp;nut\u0026nbsp;chewing\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e104(22.7%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHypertension\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e157(34.3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiabetes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e81(17.7%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiseases\u0026nbsp;of\u0026nbsp;the\u0026nbsp;\u003c/p\u003e\u003cp\u003ecardiovascular\u0026nbsp;system\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e111(24.2%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiseases\u0026nbsp;of\u0026nbsp;the\u003c/p\u003e\u003cp\u003e\u0026nbsp;urological\u0026nbsp;system\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e112(24.5%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eThyroid\u0026nbsp;disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e86(18.8%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiseases\u0026nbsp;of\u0026nbsp;the\u0026nbsp;\u003c/p\u003e\u003cp\u003erespiratory\u0026nbsp;system\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e118(25.8%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePreoperative\u0026nbsp;anxiety\u0026nbsp;\u003c/p\u003e\u003cp\u003eand\u0026nbsp;depression\u0026nbsp;state\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e205(44.8%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHistory\u0026nbsp;of\u0026nbsp;\u003c/p\u003e\u003cp\u003echemotherapy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e266(58.1%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHistory\u0026nbsp;of\u0026nbsp;\u003c/p\u003e\u003cp\u003eimmunotherapy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e136(29.7%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePreoperative\u0026nbsp;pain\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003epain\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e264(57.6%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLymph\u0026nbsp;node\u0026nbsp;size\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0cm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e178(38.9%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;3cm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e111(24.2%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3-6cm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e161(35.15%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;6cm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8(1.7%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSize\u0026nbsp;of\u0026nbsp;tumor\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;2cm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e116(25.3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2-4cm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e240(52.4%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;4cm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e102(22.3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTNM\u0026nbsp;classification\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eStage\u0026nbsp;I\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e64(14.0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eStage\u0026nbsp;II\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e80(17.5%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eStage\u0026nbsp;III\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e147(32.1%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eStage\u0026nbsp;IV\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e167(36.5%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eType\u0026nbsp;of\u0026nbsp;Cancer\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSquamous\u0026nbsp;cell\u0026nbsp;\u003c/p\u003e\u003cp\u003ecarcinoma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e420(91.7%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLocation\u0026nbsp;of\u0026nbsp;primary\u003c/p\u003e\u003cp\u003edisease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTongue\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e226(49.3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAlveolar\u0026nbsp;region\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e74(16.2%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFloor\u0026nbsp;of\u0026nbsp;the\u0026nbsp;mouth\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e32(7.0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBuccal\u0026nbsp;mucosa\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e103(22.5%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePalate\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16(3.5%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eRetro\u0026nbsp;molar\u0026nbsp;trigone\u003c/p\u003e\u003cp\u003earea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7(1.5%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eULND\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e110(24.0%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBLND\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e216(47.2%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSite\u0026nbsp;of\u0026nbsp;flap\u0026nbsp;\u003c/p\u003e\u003cp\u003etransplantation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eantebrachium\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e166(36.2%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAnterolateral\u0026nbsp;femoral\u0026nbsp;\u003c/p\u003e\u003cp\u003eskin\u0026nbsp;flap\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e207(45.2%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFibular\u0026nbsp;flap\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e24(5.2%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ecutaneous\u0026nbsp;iliac\u0026nbsp;flap\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e61(13.3%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSurgery\u0026nbsp;time\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eminute\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e370[309,435]\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eTNM Tumor Node Metastasis,ULND Unilateral lymph node dissection,BLND Bilateral lymph node dissection\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eTime-Series Analysis of Pain Severity\u003c/h3\u003e\n\u003cp\u003eThis study analyzed the dynamic evolution of pain severity across time points. Over half of the patients reported preoperative pain. In the early postoperative period (POD1\u0026ndash;POD2), \u0026gt;\u0026thinsp;80% experienced no significant pain, with low rates of other pain levels, indicating effective initial pain control. On POD3, 342 patients (74.67%) developed significant pain, stratified as mild (27 patients, 5.9%), moderate (236 patients, 51.5%), and severe (79 patients, 17.2%). By POD7, 38.9% of patients had moderate to severe pain, reflecting the dynamic progression of postoperative pain over time. Detailed data are in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\n\u003ch3\u003eAnalysis of Factors Associated with Postoperative Acute Pain in Oral Cancer Patients\u003c/h3\u003e\n\u003cp\u003eThe presence of pain was significantly correlated with educational level (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), history of diabetes mellitus (p\u0026thinsp;=\u0026thinsp;0.035), history of chemotherapy (p\u0026thinsp;=\u0026thinsp;0.007), history of immunotherapy (p\u0026thinsp;=\u0026thinsp;0.007), preoperative anxiety and depression (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and clinical lymph node involvement (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Further analysis indicated that the occurrence of postoperative acute pain was also significantly associated with tumor size (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), TNM classification (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), primary tumor site (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), approach to cervical lymph node dissection (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and type of free flap (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Detailed characteristics are presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDemographic and clinical characteristics associated with acute postoperative pain in oral cancer patients\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eVariables\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eAcute\u0026nbsp;Postoperative\u0026nbsp;Pain\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eYes(n\u0026thinsp;=\u0026thinsp;342)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNo(n\u0026thinsp;=\u0026thinsp;116)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge(years)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e51.64[50.28, 53]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e51.22[48.95,53.5]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.725\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWeight(kg)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e65.93[64.66,67.21]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e66.60[64.5,68.7]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.493\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEducation\u0026nbsp;level,\u003c/p\u003e\u003cp\u003en(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026lt;higher\u0026nbsp;education\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e209(61.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e39(33.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026gt;=higher\u0026nbsp;education\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e133(38.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e77(66.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSex,n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.88\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003emale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e266(77.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e91(78.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003efemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e76(22.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e25(21.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBetel\u0026nbsp;quid\u0026nbsp;or\u0026nbsp;\u003c/p\u003e\u003cp\u003eareca\u0026nbsp;nut\u0026nbsp;chewing,n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e82(24%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e22(19%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.266\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHypertension,n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e119(34.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e38(32.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.69\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiabetes,n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e53(15.5%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e28(24.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.035*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiseases\u0026nbsp;of\u0026nbsp;the\u0026nbsp;\u003c/p\u003e\u003cp\u003ecardiovascular\u0026nbsp;system,n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e82(24%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e29(25%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.824\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiseases\u0026nbsp;of\u0026nbsp;the\u003c/p\u003e\u003cp\u003e\u0026nbsp;urological\u0026nbsp;system,n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e84(24.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e28(24.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.927\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eThyroid\u0026nbsp;disease,n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e66(19.30%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20(17.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.624\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiseases\u0026nbsp;of\u0026nbsp;the\u0026nbsp;\u003c/p\u003e\u003cp\u003erespiratory\u0026nbsp;system,n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e90(26.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e28(24.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.643\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePreoperative\u0026nbsp;anxiety\u0026nbsp;\u003c/p\u003e\u003cp\u003eand\u0026nbsp;depression\u0026nbsp;state,n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e174(50.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e31(26.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHistory\u0026nbsp;of\u0026nbsp;\u003c/p\u003e\u003cp\u003echemotherapy,n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e211(61.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e55(47.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.007*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHistory\u0026nbsp;of\u0026nbsp;\u003c/p\u003e\u003cp\u003eimmunotherapy,n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e90(26.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e46(39.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.007*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePreoperative\u0026nbsp;pain\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e205(59.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e59(50.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.087\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLymph\u0026nbsp;node\u0026nbsp;size,n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e0cm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e113(33%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e65(56%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;3cm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e92(26.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e19(16.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e3-6cm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e130(38%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e31(26.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;6cm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7(2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1(0.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSize\u0026nbsp;of\u0026nbsp;tumor,n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;2cm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e41(12%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e75(64.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2-4cm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e208(60.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e32(27.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;4cm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e93(27.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9(7.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTNM\u0026nbsp;classification,n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStage\u0026nbsp;I\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e19(5.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e45(38.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStage\u0026nbsp;II\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e64(18.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16(13.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStage\u0026nbsp;III\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e124(36.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e23(19.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStage\u0026nbsp;IV\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e135(39.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e32(27.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eType\u0026nbsp;of\u0026nbsp;Cancer,n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.072\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSquamous\u0026nbsp;cell\u0026nbsp;\u003c/p\u003e\u003cp\u003ecarcinoma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e309(90.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e111(95.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOthers\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e33(9.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5(4.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLocation\u0026nbsp;of\u0026nbsp;primary\u003c/p\u003e\u003cp\u003edisease,n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTongue\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e152(44.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e74(63.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAlveolar\u0026nbsp;region\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e70(20.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4(3.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFloor\u0026nbsp;of\u0026nbsp;the\u0026nbsp;mouth\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e24(7.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8(6.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBuccal\u0026nbsp;mucosa\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e77(22.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e26(22.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePalate\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13(3.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3(2.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRetro\u0026nbsp;molar\u0026nbsp;trigone\u003c/p\u003e\u003cp\u003earea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6(1.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1(0.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eULND,n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e65(19%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e45(38.8%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBLND,n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e192(56.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e24(20.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSite\u0026nbsp;of\u0026nbsp;flap\u0026nbsp;\u003c/p\u003e\u003cp\u003etransplantation,n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eantebrachium\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e98(28.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e68(58.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAnterolateral\u0026nbsp;femoral\u0026nbsp;\u003c/p\u003e\u003cp\u003eskin\u0026nbsp;flap,n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e166(48.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e41(35.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFibular\u0026nbsp;flap\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e21(6.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3(2.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ecutaneous\u0026nbsp;iliac\u0026nbsp;flap\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e57(16.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4(3.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSurgery\u0026nbsp;time(min)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e371.65[360.46,382.84]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3449.66[329.04,370.27]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.207\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eTNM Tumor Node Metastasis,ULND Unilateral lymph node dissection,BLND Bilateral lymph node dissection, *P-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 by chi-square test, Fisher exact test, t-test, or Mann-Whitney U-test\u003c/p\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eMultivariate Analysis of Independent Risk Factors for Postoperative Acute Pain in Oral Cancer Patients\u003c/h2\u003e\u003cp\u003eA total of 12 potential risk factors with p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 identified in Tables\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e were included in univariate and multivariate logistic regression analyses. Multivariate results identified the following independent risk factors for acute pain on postoperative day 3: lower educational level (OR\u0026thinsp;=\u0026thinsp;0.29, 95% CI: 0.15\u0026ndash;0.58, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), no prior immunotherapy (OR\u0026thinsp;=\u0026thinsp;0.12, 95% CI: 0.04\u0026ndash;0.33, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), larger tumor size (OR\u0026thinsp;=\u0026thinsp;20.53, 95% CI: 6.9\u0026ndash;61.12, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), unilateral lymph node dissection (OR\u0026thinsp;=\u0026thinsp;3.46, 95% CI: 1.29\u0026ndash;9.26, p\u0026thinsp;=\u0026thinsp;0.014), bilateral lymph node dissection (OR\u0026thinsp;=\u0026thinsp;10.95, 95% CI: 3.25\u0026ndash;36.97, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), flap type (vs. forearm flap: anterolateral thigh flap, OR\u0026thinsp;=\u0026thinsp;2.88, 95% CI: 1.43\u0026ndash;5.79, p\u0026thinsp;=\u0026thinsp;0.003; fibular flap, OR\u0026thinsp;=\u0026thinsp;8.28, 95% CI: 1.53\u0026ndash;44.91, p\u0026thinsp;=\u0026thinsp;0.014; iliac bone flap, OR\u0026thinsp;=\u0026thinsp;10.17, 95% CI: 2.52\u0026ndash;41.00, p\u0026thinsp;=\u0026thinsp;0.001), and preoperative anxiety/depression (OR\u0026thinsp;=\u0026thinsp;2.71, 95% CI: 1.42\u0026ndash;5.20, p\u0026thinsp;=\u0026thinsp;0.003). (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eUnivariate and multivariate logistic regression analysis of postoperative acute pain in patients undergoing oral and maxillofacial tumor surgery\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eVariables\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eUnivariate\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003eMultivariate\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOR(95%CI)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eP-value\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eOR(95%CI)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eP-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEducation\u0026nbsp;level\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.32[0.21, 0.5]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.29[0.15,0.58]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiabetes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.5[0.34,0.97]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.036*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.36[0.56,3.32]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.497\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHistory\u0026nbsp;of\u0026nbsp;chemotherapy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.79[1.17,2.73]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.007*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHistory\u0026nbsp;of\u0026nbsp;immunotherapy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.54[0.35,0.85]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.007*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.12[0.04,0.33]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAdenophyma\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.58[1.68, 3.97]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.93[0.16,5.48]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.939\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSize\u0026nbsp;of\u0026nbsp;tumor(vs\u0026nbsp;\u0026lt;=2cm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;2cm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13.43[8.13,22.17]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e20.53[6.9,61.12]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTNM\u0026nbsp;classification(vs\u0026nbsp;Stage\u0026nbsp;I)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.932\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStage\u0026nbsp;II\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9.47[4.4,20.39]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.475[0.298,7,288]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.658\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStage\u0026nbsp;III\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12.77[6.36,25.63]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.983\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eStage\u0026nbsp;IV\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9.99[5.16,19.34]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.983\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLocation\u0026nbsp;of\u0026nbsp;primary\u0026nbsp;disease(tongue)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.2[1.43,3.4]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.27[0.63,2.56]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.496\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eULND\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.37[0.23,0.59]]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3.46[1.29,9.26]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.014*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBLND\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4.91[2.98,8.07]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e10.95[3.25,36.97]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSite\u0026nbsp;of\u0026nbsp;flap\u0026nbsp;transplantation(vs\u0026nbsp;antebrachium)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.039*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAnterolateral\u0026nbsp;femoral\u0026nbsp;skin\u0026nbsp;flap\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.81[1.77,4.45]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.88[1.43,5.79]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.003\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFibular\u0026nbsp;flap\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4.86[1.39,16.93]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.013*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e8.28[1.53,44.91]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.014\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCutaneous\u0026nbsp;iliac\u0026nbsp;flap\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9.89[3.43,28.54]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e10.17[2.52,41.00]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePreoperative\u0026nbsp;anxiety\u0026nbsp;and\u0026nbsp;depression\u0026nbsp;state\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.84[1.79,4.51]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.71[1.42,5.20]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.003*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eTNM Tumor Node Metastasis,ULND Unilateral lymph node dissection,BLND Bilateral lymph node dissection, OR odds ratio, CI confdence interval. *P-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003eConstruction of a Predictive Model for Postoperative Acute Pain in Oral Cancer Patients\u003c/h2\u003e\u003cp\u003eA nomogram model was developed to individually predict postoperative day 3 acute pain risk in oral cancer patients, incorporating independent risk factors identified via multivariate analysis: educational level, immunotherapy history, tumor size, lymph node dissection approach, flap type, and preoperative anxiety/depression (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA). Receiver operating characteristic (ROC) curve analysis evaluated the model\u0026rsquo;s discriminative performance, revealing a prediction cutoff value of 0.79 (sensitivity\u0026thinsp;=\u0026thinsp;0.87; specificity\u0026thinsp;=\u0026thinsp;0.86). The area under the curve (AUC) was 0.923 (95% CI: 0.895\u0026ndash;0.951), indicating excellent ability to distinguish between patients with and without postoperative acute pain. The narrow 95% CI confirmed result stability and reliability. (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eB).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003eValidation of the Nomogram Model for Predicting Postoperative Acute Pain in Oral Cancer Patients\u003c/h2\u003e\u003cp\u003eTo verify the model\u0026rsquo;s stability and generalizability, internal (training set, n\u0026thinsp;=\u0026thinsp;320) and external (validation set, n\u0026thinsp;=\u0026thinsp;138) validations were performed via R software. ROC curve analysis showed the training set yielded an AUC of 0.928 (95% CI: 0.898\u0026ndash;0.958; Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eA) and the validation set an AUC of 0.911 (95% CI: 0.849\u0026ndash;0.973; Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eB), demonstrating the model stably stratified postoperative acute pain risk across datasets with superior discriminative efficacy, and its AUC improved by \u0026gt;\u0026thinsp;0.2 vs. single-indicator prediction. Calibration curves (Figs.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eC, \u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eD) assessed by the Hosmer-Lemeshow test confirmed consistency with the ideal model in both sets (training set: P\u0026thinsp;=\u0026thinsp;0.885; validation set: P\u0026thinsp;=\u0026thinsp;0.804; both P\u0026thinsp;\u0026gt;\u0026thinsp;0.05), validating predictive accuracy and stable calibration. DCA (Figs.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eE, \u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eF) showed the nomogram outperformed \u0026ldquo;no model\u0026rdquo; and \u0026ldquo;AI-only\u0026rdquo; strategies across sets; at high-risk thresholds (0.1\u0026ndash;0.9), its net benefit curve was higher, and within 0.3\u0026ndash;0.7 (critical for decisions), it identified 8\u0026ndash;12 more true pain cases per 100 patients while avoiding 5\u0026ndash;7 over-analgesia instances. Subgroup analyses by tumor sites (tongue, buccal, gingival) showed the tongue subgroup\u0026rsquo;s AUC of 0.902 (95% CI: 0.800\u0026ndash;1; P\u0026thinsp;=\u0026thinsp;0.534 vs. overall) confirmed generalizability, and age-stratified analysis found the elderly subgroup (\u0026gt;\u0026thinsp;60 years) had an AUC of 0.996 (95% CI: 0.986\u0026ndash;1) with no age-related difference (P\u0026thinsp;=\u0026thinsp;0.332), demonstrating stability. Thus, the nomogram exhibits excellent discriminative ability, accuracy, and clinical utility, validated across datasets and subgroups to guide individualized analgesic regimens and optimize perioperative outcomes for oral cancer patients.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis retrospective analysis of 458 oral cancer patients undergoing free flap reconstruction represents the first systematic investigation to delineate the prevalence of postoperative acute pain, identify multidimensional independent risk factors, and develop a nomogram model with robust predictive performance (AUC\u0026thinsp;=\u0026thinsp;0.923). These findings offer novel insights into the pathophysiological mechanisms of postoperative pain in oral cancer and establish a foundation for individualized pain management strategies. The observed 74.6% prevalence of postoperative pain aligns with broader head and neck malignancy epidemiological data: Khawaja et al. documented that up to 70% of such patients experience pain[12], while Imani et al.emphasized that surgery and radiotherapy frequently induce acute and chronic discomfort[13]. The marginally higher rate in oral cancer may stem from dual orofacial surgical trauma and flap donor-site injury, compounded by the oral cavity\u0026rsquo;s dense trigeminal innervation (3\u0026ndash;5-fold higher nerve density in tongue/gingiva than trunk skin)[7]. Surgical trauma damages nerve fibers and activates TRPV1/P2X3 receptors[14], inducing primary afferent sensitization, while postoperative functional activities (swallowing, speech) perpetuate mechanical stimulation, amplifying pain distinct from non-oral malignancies[15].\u003c/p\u003e\u003cp\u003ePatients received standardized patient-controlled intravenous analgesia (PCIA: hydromorphone 0.1 mg/kg\u0026thinsp;+\u0026thinsp;ketamine 0.1 mg/kg\u0026thinsp;+\u0026thinsp;0.9% sodium chloride 100 mL at 2 mL/h) for 48 postoperative hours, with marked efficacy: pain incidence was 16.8% (median NRS 0, IQR 0\u0026ndash;2) on day 1 and 19.7% (median NRS 0, IQR 0\u0026ndash;2) on day 2. Due to logistical and cost constraints, PCIA was not continued beyond 48 hours, contributing to a sharp escalation in pain incidence to 74.6% on day 3. This corroborates Orgill et al.\u0026rsquo;s finding that \"only 35% of head and neck cancer patients achieve adequate pain control,\" [16]underscoring a critical management challenge. Among patients with NRS\u0026thinsp;\u0026ge;\u0026thinsp;1 on day 3, only a subset required NSAID intervention, while others declined medication. Given potential bias from variable medication utilization, later NRS scores (e.g., day 7) were excluded from incidence analyses.\u003c/p\u003e\u003cp\u003eTumor size emerged as a prominent independent risk factor. Larger tumors involve broader infiltration, heightened metastatic potential, and extensive invasion of adjacent tissues, nerves, and bone. Resection induces greater iatrogenic damage, with postoperative inflammatory responses (e.g., 3\u0026ndash;5-fold elevations in IL-6 and TNF-α) correlating positively with tumor diameter[17]. TNM staging analyses revealed stepwise pain incidence increases (stage I: 14.0% vs. stage IV: 36.5%), validating tumor burden\u0026rsquo;s impact. Surgical approach strongly associates with pain via resection extent, tissue trauma, and nerve exposure risk.\u003c/p\u003e\u003cp\u003ePatients undergoing bilateral cervical lymph node dissection faced higher pain risk (OR\u0026thinsp;=\u0026thinsp;10.95) than unilateral dissection (OR\u0026thinsp;=\u0026thinsp;3.46), attributable to bilateral spinal accessory nerve and cervical plexus (C2\u0026ndash;C4) injury: spinal accessory damage induces trapezius denervation and shoulder pain, while cervical plexus injury causes anterior neck dysesthesia. Nerve regeneration in levator scapulae is 40% slower after bilateral dissection, prolonging pain[1]. Flap type analyses showed iliac bone flaps conferred higher risk (OR\u0026thinsp;=\u0026thinsp;10.17) than other free flaps, reflecting greater donor-site trauma (93% pain incidence vs. 59% with forearm flaps)[18]. Iliac flap harvest transects gluteus maximus attachments and superior gluteal nerve deep branches, with osseous resection inducing more intense pain than soft-tissue dissection. Preoperative anxiety and depression reinforce the \"psycho-neuro-immune axis\" in pain modulation[19]. They upregulate hypothalamic-pituitary-adrenal axis activity, elevating cortisol and lowering pain thresholds, while promoting inflammatory mediator release (CRP, IL-1β) to perpetuate a \"pain-anxiety\" loop [20],[21].\u003c/p\u003e\u003cp\u003ePatients with abnormal preoperative HADS scores had nearly 3-fold increased pain risk, highlighting preoperative psychological intervention as a potential adjunct. Educational level associations likely reflect health literacy disparities: patients with \u0026le;\u0026thinsp;junior high education demonstrated poorer comprehension of pain assessment tools and communication with providers, potentially delaying intervention[22]. This subgroup\u0026rsquo;s higher pain incidence may also relate to delayed presentation (larger surgical defects), economic constraints, and inadequate insurance, leading to passive pain tolerance. Higher-educated patients may better utilize cognitive-behavioral strategies for pain management[23][24].\u003c/p\u003e\u003cp\u003eNotably, immunotherapy history emerged as a protective factor. Immune checkpoint inhibitors may modulate pain via neuro-immune crosstalk, suppressing macrophage secretion of nerve injury factors (e.g., NGF) and enhancing T-cell-mediated clearance of damaged nerves, mitigating neuropathic pain[25][26]. The gut microbiome-immune axis also influences pain through immunomodulation[27], while adequate pain control can reverse immunosuppression, improving immune status. However, limited sample size necessitates multicenter studies to clarify pathways and long-term effects.\u003c/p\u003e\u003cp\u003eThis study\u0026rsquo;s innovations are threefold: first, granular pain risk stratification across demographic, tumor-related, surgical, and psychological domains. Second, advanced multivariate predictive modeling via a nomogram (AUC\u0026thinsp;=\u0026thinsp;0.923) enabling \"preoperative-intraoperative-postoperative\" risk prediction, aligned with ERAS \"preventive analgesia.\" Third, identification of a critical gap: 48-hour PCA insufficiently controls complex pain (51.5% moderate, 17.2% severe on day 3), necessitating optimized multimodal analgesia and extended duration.\u003c/p\u003e\u003cp\u003eLimitations include retrospective bias with unrecorded variables (e.g., intraoperative opioids, infections). Pain assessment was restricted to 7 days, lacking chronic pain evaluation; prospective studies are needed for long-term outcomes. Mechanistic insights are limited by absent biomarker analyses (e.g., COMT polymorphisms, cytokines). Single-center data may reflect regional practices, requiring multicenter validation. Future research should prioritize replication and mechanistic investigations.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study confirms high prevalence and multifactorial etiology of acute postoperative pain in oral cancer. The nomogram provides a robust tool for risk stratification and individualized management. Future research will refine precision pain prevention through mechanistic studies and translational validation.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eNRS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eNumerical rating scale\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eDCA\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eDecision curve analysis\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eOR\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eOdds ratio\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eAUC\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eArea under the curve\u0026zwnj;\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eERAS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eEnhanced recovery after surgery\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eNSAIDs\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eNon-steroidal anti-inflammatory drugs\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003ePOD\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ePostoperation day\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eTNM\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eTumor node metastasis\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eULND\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eUnilateral lymph node dissection\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eBLND\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eBilateral lymph node dissection\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCRP\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ecAMP receptor protein\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eHADS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eHospital anxiety and depression scale\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eNGF\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eNerve growth factor\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003ePCA\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ePatient-controlled analgesia\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated or analyzed during this study are included in this published article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study is a retrospective analysis of medical record data. No external funding was received during the research design, data collection, analysis, or manuscript preparation process. There was no specific institutional or departmental funding support for this study.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study received no funding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics declarations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was reviewed and approved by the Ethics Committee of the Hospital of Stomatology, Wuhan University (Approval number:[2023] Lun Shen Zi (B11))on April 12, 2023.All patients enrolled for the study signed an informed consent.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFang Qi: contributed to the design, and acquisition, analysis, and interpretation of data; drafted the manuscript and critically revised manuscript. Yiqun Kang: contributed to the design and acquisition of data, \u0026nbsp;critically revised manuscript.. Long Zuo: contributed to acquisition and interpretation of data, critically revised manuscript. LiangYu Chen: contributed to conception and acquisition of data, critically revised manuscript. Yuan Yu: contributed to conception and acquisition of datacritically revised manuscript. Tuo Ji: contributed to conception and acquisition of data, critically revised manuscript.Wei Peng: contributed to interpretation of data, critically revised manuscript. Tiejun Zhan: Contributed to interpretation of data, critically revised manuscript. Li Wang: contributed to conception and design, and acquisition, analysis, and interpretation of data; drafted the manuscript and critically revised it for important intellectual content. All authors gave final approval and \u0026nbsp;agreed to be accountable for all aspects of work ensuring integrity and accuracy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors declare that there are no financial conflicts of interest, personal conflicts of interest, or other potential conflicts of interest related to the subject of this study in the process of conducting the research and publishing this manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F: Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. 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Pharmaceuticals (Basel) 2024, 17(4).\u003c/li\u003e\n\u003cli\u003eChen D, Yang H, Yang L, Tang Y, Zeng H, He J, Chen W, Qu Y, Hu Y, Xu Y et al: Preoperative psychological symptoms and chronic postsurgical pain: analysis of the prospective China Surgery and Anaesthesia Cohort study. Br J Anaesth 2024, 132(2):359-371.\u003c/li\u003e\n\u003cli\u003eIng JW: Head and Neck Cancer Pain. Otolaryngol Clin North Am 2017, 50(4):793-806.\u003c/li\u003e\n\u003cli\u003eHinther A, Nakoneshny SC, Chandarana SP, Wayne Matthews T, Dort JC: Efficacy of postoperative pain management in head and neck cancer patients. J Otolaryngol Head Neck Surg 2018, 47(1):29.\u003c/li\u003e\n\u003cli\u003eHoofwijk DMN, van Reij RRI, Rutten BPF, Kenis G, Theunissen M, Joosten EA, Buhre WF, van den Hoogen NJ: Genetic polymorphisms and prediction of chronic post-surgical pain after hysterectomy-a subgroup analysis of a multicenter cohort study. Acta Anaesthesiol Scand 2019, 63(8):1063-1073.\u003c/li\u003e\n\u003cli\u003eMi X, Zou B, Rashidi P, Baharloo R, Fillingim RB, Wallace MR, Crispen PL, Parvataneni HK, Prieto HA, Gray CF et al: Effects of Patient and Surgery Characteristics on Persistent Postoperative Pain: A Mediation Analysis. Clin J Pain 2021, 37(11):803-811.\u003c/li\u003e\n\u003cli\u003eArmstrong RA, Fayaz A, Manning GLP, Moonesinghe SR, Peri-operative Quality Improvement Programme delivery t, Oliver CM, collaborative P: Predicting severe pain after major surgery: a secondary analysis of the Peri-operative Quality Improvement Programme (PQIP) dataset. Anaesthesia 2023, 78(7):840-852.\u003c/li\u003e\n\u003cli\u003eImani F, Mohebbi S, Mohseni M, Karimi B, Rahimi S, Dikafraz Shokooh GA: A Narrative Review on Pain Management in Head and Neck Cancer: Integrating Multimodal Analgesia and Interventional Procedures. Anesth Pain Med 2024, 14(3):e146825.\u003c/li\u003e\n\u003cli\u003eZhong W, Ma X, Xing Y, Kim DK, Wang A, Jiang W, Xu T: Blockade of peripheral nociceptive signal input relieves the formation of spinal central sensitization and retains morphine efficacy in a neuropathic pain rat model. Neurosci Lett 2020, 716:134643.\u003c/li\u003e\n\u003cli\u003eYe Y, Jensen DD, Viet CT, Pan HL, Campana WM, Amit M, Boada MD: Advances in Head and Neck Cancer Pain. J Dent Res 2022, 101(9):1025-1033.\u003c/li\u003e\n\u003cli\u003eOrgill R, Krempl GA, Medina JE: Acute pain management following laryngectomy. Arch Otolaryngol Head Neck Surg 2002, 128(7):829-832.\u003c/li\u003e\n\u003cli\u003eKhawaja SN, Jamshed A, Hussain RT: Prevalence of pain in oral cancer: A retrospective study. Oral Dis 2021, 27(7):1806-1812.\u003c/li\u003e\n\u003cli\u003eEkstein MP, Weinbroum AA: Immediate postoperative pain in orthopedic patients is more intense and requires more analgesia than in post-laparotomy patients. Pain Med 2011, 12(2):308-313.\u003c/li\u003e\n\u003cli\u003eYang MMH, Hartley RL, Leung AA, Ronksley PE, Jette N, Casha S, Riva-Cambrin J: Preoperative predictors of poor acute postoperative pain control: a systematic review and meta-analysis. BMJ Open 2019, 9(4):e025091.\u003c/li\u003e\n\u003cli\u003eFranqueiro AR, Wilson JM, He J, Azizoddin DR, Karamnov S, Rathmell JP, Soens M, Schreiber KL: Prospective Study of Preoperative Negative Affect and Postoperative Pain in Patients Undergoing Thoracic Surgery: The Moderating Role of Sex. J Clin Med 2024, 13(19).\u003c/li\u003e\n\u003cli\u003eNiklasson A, Finan PH, Smith MT, Forsberg A, Dietz N, Kander T, Werner MU, Irwin MR, Kosek E, Bjurstrom MF: The relationship between preoperative sleep disturbance and acute postoperative pain control: A systematic review and meta-analysis. Sleep Med Rev 2025, 79:102014.\u003c/li\u003e\n\u003cli\u003evan Lankveld W, Afram B, Staal JB, van der Sande R: The IASP pain curriculum for undergraduate allied health professionals: educators defining competence level using Dublin descriptors. BMC Med Educ 2020, 20(1):60.\u003c/li\u003e\n\u003cli\u003eWideman TH, Miller J, Bostick G, Thomas A, Bussieres A, Wickens RH: The current state of pain education within Canadian physiotherapy programs: a national survey of pain educators. Disabil Rehabil 2020, 42(9):1332-1338.\u003c/li\u003e\n\u003cli\u003eZhang C, Li Y, Yu Y, Li Z, Xu X, Talifu Z, Liu W, Yang D, Gao F, Wei S et al: Impact of inflammation and Treg cell regulation on neuropathic pain in spinal cord injury: mechanisms and therapeutic prospects. Front Immunol 2024, 15:1334828.\u003c/li\u003e\n\u003cli\u003eHo MFS, Farkas O, Faria AV, Plemel JR, Kerr BJ: A recent history of immune cell sex differences in the peripheral nervous system in persistent pain states. Brain Behav Immun 2025, 128:766-775.\u003c/li\u003e\n\u003cli\u003eSantoni M, Miccini F, Battelli N: Gut microbiota, immunity and pain. Immunol Lett 2021, 229:44-47.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-oral-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ohea","sideBox":"Learn more about [BMC Oral Health](http://bmcoralhealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ohea/default.aspx","title":"BMC Oral Health","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"pain prediction, risk stratification, individualized analgesia, perioperative pain management, nomogram validation","lastPublishedDoi":"10.21203/rs.3.rs-7471981/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7471981/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThis study aimed to determine the incidence and independent risk factors of acute postoperative pain in oral cancer patients and develop an individualized predictive nomogram. A retrospective cohort study included 458 oral cancer patients who underwent tumor resection with free flap reconstruction at Wuhan University\u0026rsquo;s Hospital of Stomatology (January 2023\u0026ndash;December 2024). Demographics, medical history, tumor features, surgical variables, and preoperative anxiety/depression were collected. Pain intensity was assessed using the Numerical Rating Scale (NRS) on postoperative days 1, 2, 3, and 7. Independent risk factors were identified via multivariate analysis, and a nomogram was validated using ROC curves, calibration curves, and Decision Curve Analysis (DCA). The incidence of acute pain on postoperative day 3 was 74.67% (342/458), with 51.5% experiencing moderate pain (NRS 4\u0026ndash;6) and 17.2% severe pain (NRS\u0026thinsp;\u0026ge;\u0026thinsp;7). Independent risk factors included education\u0026thinsp;\u0026le;\u0026thinsp;junior high school (OR\u0026thinsp;=\u0026thinsp;0.29), no history of immunotherapy (OR\u0026thinsp;=\u0026thinsp;0.12), larger tumor volume (OR\u0026thinsp;=\u0026thinsp;20.53), unilateral (OR\u0026thinsp;=\u0026thinsp;3.46) or bilateral lymph node dissection (OR\u0026thinsp;=\u0026thinsp;10.95), free flap type (OR\u0026thinsp;=\u0026thinsp;10.17), and preoperative anxiety/depression (OR\u0026thinsp;=\u0026thinsp;2.71; all P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). The nomogram showed excellent performance (AUC\u0026thinsp;=\u0026thinsp;0.923; training/validation sets: 0.928/0.911), with high consistency between predicted and actual incidence (Hosmer-Lemeshow test, P\u0026thinsp;\u0026gt;\u0026thinsp;0.05) and significant clinical net benefits (DCA). In conclusion, acute postoperative pain in oral cancer is common and multifactorial. The nomogram accurately predicts this risk, aiding individualized analgesia and optimizing pain management.\u003c/p\u003e","manuscriptTitle":"Risk Factors and Development of a Predictive Nomogram Model for Acute Postoperative Pain in Oral Cancer","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-08 07:25:21","doi":"10.21203/rs.3.rs-7471981/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-12-19T08:45:28+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-17T02:28:17+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"290749889639839159294070202528710362988","date":"2025-12-17T01:35:38+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-25T11:20:32+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-19T13:12:21+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"214961324147057419187849456371310392982","date":"2025-11-17T11:38:53+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"50265773322582904680870989011415688048","date":"2025-11-15T02:29:43+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-07T03:17:31+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"222331090356181328696075777884128988378","date":"2025-11-07T02:57:21+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-09-25T01:07:56+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-09-12T07:51:52+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-09-08T14:06:37+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-09-08T14:05:19+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Oral Health","date":"2025-08-27T12:58:42+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-oral-health","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ohea","sideBox":"Learn more about [BMC Oral Health](http://bmcoralhealth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/ohea/default.aspx","title":"BMC Oral Health","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ed7d93f5-fe0a-4558-9d1b-0b8bcac492f9","owner":[],"postedDate":"October 8th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-02-09T16:01:57+00:00","versionOfRecord":{"articleIdentity":"rs-7471981","link":"https://doi.org/10.1186/s12903-026-07792-y","journal":{"identity":"bmc-oral-health","isVorOnly":false,"title":"BMC Oral Health"},"publishedOn":"2026-02-04 15:58:37","publishedOnDateReadable":"February 4th, 2026"},"versionCreatedAt":"2025-10-08 07:25:21","video":"","vorDoi":"10.1186/s12903-026-07792-y","vorDoiUrl":"https://doi.org/10.1186/s12903-026-07792-y","workflowStages":[]},"version":"v1","identity":"rs-7471981","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7471981","identity":"rs-7471981","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}