Conventional versus high-voltage, long-term pulse Radiofrequency of ganglion impar in perineal pain with advanced rectal cancer: A Randomized, Double-Blind Controlled Trial

Conventional versus high-voltage, long-term pulse Radiofrequency of ganglion impar in perineal pain with advanced rectal cancer: A Randomized, Double-Blind Controlled Trial | 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 Conventional versus high-voltage, long-term pulse Radiofrequency of ganglion impar in perineal pain with advanced rectal cancer: A Randomized, Double-Blind Controlled Trial Qin Li, Huaiming Wang, Bo Zhong, Taomei Zhang, Zhiqiang Wang, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4149738/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective Advanced rectal cancer is a common cause of perineal pain and research on the use of radiofrequency therapy for the treatment of this pain is limited. In the present study, we aimed to compare the effectiveness and safety of conventional radiofrequency (CRF) and high-voltage long-term pulsed radiofrequency (H-PRF) of radiofrequency therapy in the management of perineal pain in advanced rectal cancer. Methods A total of 72 patients with advanced rectal cancer experiencing perineal pain were enrolled and randomly assigned to either the group CRF or H-PRF in a double-blind trial. The primary focus was on assessing perineal pain using NRS scores at various time points. Secondary outcomes included the duration of maintaining a sitting position, depression scores, sleep quality, consumption of Oral Morphine Equivalent and Pregabalin, and the incidence of perineal numbness. Results A total of 57 patients (28 patients in the group CRF and 29 patients in the H- group H-PRF) were investigated. At all observation time points postoperatively, both groups of patients exhibited significant reductions in pain, enhancements in depression, improvements in sleep quality, and increased duration of sitting compared to their baseline measurements ( P ＜0.05). During the 3 months and 6 months follow-up period, the group CRF exhibited significant reduction in pain, improvement in depression, sleep quality, and increased the time of keeping a sitting position compared with the group H-PRF. ( P ＜0.05). The consumption of oral morphine equivalent and Pregabalin as well as the incidence of perineal numbness were not significantly different between groups ( P >0.05). Conclusion Our results demonstrate that application of CRF and H-PRF in ganglion impar to reduce perineal pain and improve the quality of life of patients with advanced rectal cancer is safe and effective. However, the long-term effect of CRF is better compared with that of H-PRF. Trial registration This study was registered was registered with the Chinese Clinical Trial Registry (ChiCTR2200061800, 07/02/2022). ganglion impar conventional radiofrequency pulsed radiofrequency perineal pain cancer pain Figures Figure 1 Figure 2 Introduction Pain is a prevalent symptom among patients with advanced diseases, with approximately 59% of patients undergoing cancer treatment, 64% of patients with advanced disease, and 33% of patients receiving curative treatment reporting pain [1]. In addition, 10-20% of cancer patients may experience refractory cancer pain [2]. Pain associated with advanced rectal cancer typically manifests in the perineum, abdomen, and lower back, with perineal pain being particularly pronounced. This discomfort significantly impacts the quality of life of patients [3]. The ganglion impar is located anterior to the articulation of the sacrum and coccyx, and it is innervated by sympathetic and parasympathetic nerve fibers originating from the lumbosacral region. It modulates the transmission of signals related to nociceptive pain and sympathetic nerve pain in the perineum [4].The ganglion impar (GIB), also known as Walters' block, is an easy and efficacious technique for targeting pelvic and perineal nociceptive pathways[5], GIB has demonstrated good efficacy in managing perineal pain [6]. The clinical application of GIB has been extended to include drug blocking, chemical damage, and radiofrequency therapy [7]. Accumulating evidence indicates that Ganglion Impar Radiofrequency (RF) can alleviate cancer-related and non-cancer-related pain[8, 9]. There are two modes of radiofrequency: conventional radiofrequency (CRF) and pulsed radiofrequency (PRF). CRF is safe and effective in treating sympathetic ganglia, whereas PRF exhibits limited therapeutic efficacy [9]. Following the application of the ganglion impar high-voltage long-term pulsed radiofrequency (H-PRF) regimen, the remission rate of pudendal neuralgia remained high at 88.6% even after 3 months [10], making it a promising strategy for the treatment of cancerous perineal pain [8]. Nevertheless, few studies have directly compared the effectiveness of CRF versus H-PRF in the management of cancer-related perineal pain. The aim of this study was to evaluate the efficacy and safety of CRF and H-PRF of the ganglion impar in the management of perineal pain associated with advanced rectal cancer. Methods Study design and randomization This pilot study, conducted at the Department of Anesthesiology at Sichuan Cancer Hospital & Institute and Yanjiang District People's Hospital, was a randomized, double-blind controlled trial registered with the Chinese Clinical Trial Registry (ChiCTR2200061800). The study was approved by the Medical Ethics Committee of the Ziyang People's Hospital (KY-sj-2023-02) and all procedures were carried out in compliance with the Declaration of Helsinki. Prior to any procedures, written informed consent was obtained from the participants. To achieve a double-blind procedure, two physicians attended the participants at each center. One physician conducted assessments while the other managed randomization and device instructions. Subjects were informed about potential sensations during treatment and instructed not to disclose them to the assessing physician. A clinical nurse who was not involved in the process of designing the protocol, assigned randomization numbers and allocated 72 patients into either the group CRF or H-PRF at a 1:1 ratio. The treatment allocation was conducted in line with a predetermined randomization list generated using random blocks. Subjects Both male and female patients attending the pain clinic were assessed to determine their eligibility and those that met the criteria were asked to participate in the study. The inclusion and exclusion criteria were assessed within the Department of Anesthesiology. Inclusion criteria: Pathologically confirmed diagnosis of rectal cancer, Cancerous pain with perineal pain, Ineffective perineal pain relief after oral opioid analgesics combined with pregabalin, willingness to accept invasive interventions, Positive symptoms of the Grading System for Neuropathic Pain (GSNP) with a score of 3 or 4[11], Life expectancy of at least 6 months, Perineal pain with the following characteristics: (1) the pain was significantly Aggravated when sitting down, (2) the pain did not affect sleep at night, (3) the pain was not accompanied by objective sensory impairment, (4) the pain in the anal area was reduced after the diagnostic nerve block of the azygous ganglion. Exclusion criteria： Lumbosacral fracture or local anatomical variation that makes it difficult to puncture, Systemic bacteremia or local infection at the puncture site, There are symptoms such as coagulation system diseases, diabetes, peptic ulcers, infections, and mental and psychological diseases, Developed recent myocardial infarction, severe bradyarrhythmia, or heart block. Intervention Once patients were admitted to undergo intervention surgery, standard indoor monitoring procedures were implemented. These procedures involved assessing the patient's blood pressure, heart rate, respiration, pulse, and pulse oxygen saturation. The patient was then positioned in a prone position on the surgical treatment bed, and the disinfected following standard protocols. Next, the sacral and coccyx regions were visualized using oblique fluoroscopy to identify the needle insertion point, specifically the first coccyx joint space. Local anesthesia was administered prior to needle insertion under oblique fluoroscopy. With the assistance of digital subtraction angiography (DSA), the depth of the needle tip was ascertained using anteroposterior and lateral fluoroscopy. Finally, following the injection of 0.5ml of contrast agent and the reconstruction of the XperCT image, the needle tip was repositioned behind the rectum and in front of the anterior longitudinal ligament of the coccyx. (refer to Fig 1). Radiofrequency electrode position test: Once the needle tip was determined, 50Hz, 0.1-0.6V stimulation was applied to induce discharge-like pain in the ganglionic innervation area, to achieve regular beating of perineal muscles at 2Hz and 0.5-2.0V, which confirmed successful targeting of the electrode position. Patients in the group CRF underwent a continuous opening procedure starting at 50°C for 30 seconds, followed by 55°C for 30 seconds, with a gradual increase in temperature to 60°C-70°C for 60 seconds, 75°C for 120 seconds, and 80°C for 180 seconds. After surgery, approximately 4ml of 0.5% ropivacaine was administered to alleviate pain associated with local heat injury. In the H-PRF group, the radiofrequency instrument was re-configured to the manual pulse mode with specific parameters including a temperature of 42°C, frequency of 2 Hz, pulse duration of 20 ms, time duration of 900 s, and an initial pulsed RF field strength of 40 V which was incrementally raised to the maximum tolerable level by the patient (up to 100 V). The patient was monitored for 10 minutes post-treatment for abnormalities. Subsequently, they were returned to the ward where vital signs were also monitored using an electrocardiogram. The patient was instructed to lie on their back for 3 hours, and changes in lower limb blood flow were observed. Collected Data The data collection and patient assessment were conducted by a well-trained pain physician who was blinded to the technique utilized. During subsequent visits, patients were prohibited from reviewing their previous data. Assessments The patients were evaluated at multiple time intervals, including baseline (pre-surgery), 24 hours following surgery, 1 week after surgery, 1month post-surgery, 3 months post-surgery, and 6 months post-surgery. The demographic data collected included age, weight, Body Mass Index (BMI), duration of the pain procedure, initial numeric rating scales (NRS), GSNP, initial total daily dose of morphine and pregabalin, and duration of medication treatment. a) Primary Outcome Pain intensity was evaluated using the Numerical Rating Scale (NRS), which ranged from 0 to 10. A 10 cm scale was employed to measure pain levels, with zero representing the absence of pain and 10 representing the most severe pain [12]. b) Secondary Outcome 1) The PHQ-9 self-rating scale was employed to evaluate the severity of depression, consisting of nine items. Despite its brevity, the scale demonstrated good reliability and validity. Scores ranging from 5 to 10 indicated mild depression, 10 to 15 indicated moderate depression, 15 to 20 indicated moderately severe depression, and scores exceeding 20 indicated severe depression [13]. 2) The Pittsburgh Sleep Quality Index (PSQI) has been widely applied in the assessment of sleep quality among patients with sleep disorders and is commonly utilized to evaluate sleep patterns in individuals experiencing pain. Questionnaire data revealed that scores on the PSQI ranged from 0 to 5, indicating good sleep, 6 to 10 representing fair sleep, 11 to 15 indicating average sleep, and 16 to 21 corresponding to poor sleep [14]. 3) The duration of maintaining a sitting position was recorded as the period within which a patient remained seated in a comfortable position until the onset of anal pain and the subsequent inability to maintain a seated position. These data were monitored by nurses during the patient's hospital stay period, and family members were trained to perform accurate recording during the post-hospitalization follow-up period[15]. 4) The opioid dosage administered preoperatively was quantified by converting it to morphine equivalent units, and the dosage of pregabalin was determined. The occurrence of anal numbness post-treatment, as well as any additional complications, was documented. Sample size calculation Due to limited epidemiological data on the prevalence of rectal cancer presenting with perineal pain, this study was exploratory in nature and did not involve sample size calculations. Statistics Satistical analysis was performed using the SPSS 22.0 software (IBM, Beijing, China, 2017). Normally distributed continuous data were presented as mean ± standard deviation (Mean ± SD). Independent samples t-test was employed to compare two groups, while repeated measures ANOVA was conducted to compare multiple groups. Non-normally distributed continuous data were summarized using the median (M) and interquartile range (IQR). Group comparisons were conducted using the rank sum test, while count data were analyzed using the chi-square test or Fisher exact probability method. Rank data were compared using the rank sum test. A P -value < 0.05 was considered to be statistically significant. Results Patent and Clinician Characteristics Initially, 72 patients were screened at the Sichuan Cancer Hospital & Institute and Yanjiang District People's Hospital. Among them, 12 individuals were excluded. Six cases were excluded due to failure to meet inclusion criteria, two cases due to the presence of heart block, and three cases due to sacrococcygeal area infection. Consequently, 60 patients were enrolled in the study, with three individuals withdrawn due to lack of follow-up resulting from mortality. Consequently, the final analysis included 57 patients, consisting of 32 males and 25 females within the cohort (Fig. 2), the patient characteristics are outlined in Table 1. Efficacy The NRS scores significantly decreased at the intervals of 24 hours, 1 week, 1 month, 3 months, and 6 months post-procedure compared to baseline in both groups ( P ＜0.001). The NRS scores were significantly lower at the 3-month ( P ＜0.002) and 6-month ( P ＜0.005) time points in group CRF compared to group H-PRF. Notably, there were no significant differences in pain levels between the two groups before the procedure, and at the 24-hour, 1-week, and 1-month follow-up assessments. Table 2 shows that patients in group CRF had better analgesic outcomes compared to those in group H-PRF, as indicated by repeated measures analysis of variance ( P <0.001). Our results indicated that PHQ-9 scores were significantly decreased at the time intervals of 24 hours, 1 week, 1 month, 3 months and 6 months post-procedure compared to baseline in both groups ( P ＜0.001). Moreover, significantly lowerPHQ-9 scores were recorded at the 3-month ( P ＜0.001) and 6-month ( P ＜0.012) time points in group CRF compared to group H-PRF. There were no significant differences in depression levels between the two cohorts before the intervention, as well as during the 24-hour, 1-week, and 1-month post-procedure, as depicted in Table 2. Patients in both groups exhibited enhanced sleep quality as lower pain levels, indicated by a decrease in PSQI scores starting 24 hours post-surgery and reaching their lowest point 1-month post-surgery before gradually increasing. Moreover, both groups demonstrated a significant reduction in PSQI scores at all postoperative time points compared to preoperative scores ( P 0.05). However, the PSQI score of the group H-PRF was significantly higher compared with that of group CRF at 3 months and 6 months post-procedure following the operation ( P <0.05), as showed in Table 2. After receiving treatment, the duration of time spent in a seated position by two groups of patients initially increased within 24 hours post-surgery, reached its highest point at 1-week post-surgery, and then gradually decreased. The study found significantly lower sitting-position measurements at both the 3-month (P < 0.009) and 6-month (P < 0.001) time points in group CRF compared to group H-PRF. Prior to the procedure, as well as at the 24-hour, 1-week, and 1-month follow-up assessments, there were no significant differences in the duration of time spent in a seated position between the two groups ( P ＞0.05), as showed in Table 2. Oral morphine equivalent and Pregabalin consumption Patients in both groups experienced rectal and perineal pain, a common consequence of rectal cancer. While radiofrequency therapy successfully reduced perineal pain, oral medications, especially morphine, were still necessary to manage pain in other areas caused by the cancer. Analysis of data shown in Table 3 showed no significant differences ( P >0.05) in daily oral morphine equivalent and pregabalin dosage between the two patient groups before and 6 months post-surgery. Safety Table 4 indicate that neither group of patients experienced adverse events such as significant bleeding at the puncture site, local infection, or rectal injury. Primary postoperative side effect observed was numbness in the perineum. In the CRF group, 16 cases (57.1%) reported perineal numbness 24 hours postoperatively, with 6 cases (21.4%) demonstrating persistent symptoms at the 6-month follow-up. Similarly, in the H-PRF group, numbness was reported by 15 cases (51.6%) at the 24-hour mark, with 8 cases (27.5%) still experiencing unresolved symptoms at the 6-month assessment. . Discussion In this study, we adopted a double-center, randomized, active-controlled, double-blind clinical trial design to investigate the safety and efficacy of CRF and H-PRF in the treatment of perineal pain and improvement of quality of life in patients with advanced rectal cancer by targeting the ganglion impar. The results demonstrated that the long-term effectiveness of CRF exceeded that of H-PRF. Occurrence of primary perineal pain has been linked to sympathetic sensory coupling, and the ganglion impar is the distal ganglion of the sympathetic chain [16]. Bocking the ganglion impar can significantly alleviate perineal pain and decrease the need for opioid analgesics [6]. Radiofrequency therapy is an effective technique for the management of ganglion impar. Radiofrequency pain treatment can be categorized into two modes: continuous radiofrequency ablation (CRF) and pulsed radiofrequency (PRF)[17]. Previous studies showed that patients experiencing primary perineal pain can experience a significant reduction in pain over a 6-month monitoring period following treatment with pulsed radiofrequency in the ganglion impar [18]. Nicholas A Zacharias et al. found that PRF and CRF can alleviate sympathetic nerve-mediated pain, including the ganglion impar. Notably, CRF showed better long-term effects in controlling noncancerous perineal pain [19]. In addition, PRF combined with plexus chemical destruction can achieve long-term pain control [20]. The aforementioned studies demonstrate that PRF is still not ideal for long-term relief of perineal pain. High-voltage pulsed radiofrequency (H-PRF) has a pronounced neuromodulatory effect by generating a robust electric field [8]. Furthermore, H-PRF demonstrates a lasting thermal damage effect, although significantly less pronounced than that observed with CRF techniques. Consequently, H-PRF is an innovative PRF modality that exhibits partial continuous thermal effects and a high-voltage, high-field-strength electric field [21, 22]. Cheng-Long Wang et al. found that H-PRF provided pain relief lasting beyond 12 weeks in individuals diagnosed with pudendal neuralgia, concurrently enhancing mood and overall quality of life [10]. The above results offer compelling evidence confirming that H-PRF treatment yielded significant analgesic effects, alleviated depression, enhanced sitting time, and improved sleep quality in group H-PRF at the six-month follow-up period. In addition, the analgesic efficacy of the H-PRF group was significantly poor compared with that of the CRF group at the 3-month follow-up. This difference may stem from the more precise ablation of the dorsal root ganglion sensory nerve by CRF [23], along with the observation that the duration of pain relief for neuropathic pain with H-PRF using the PRF mode persisted for 3 months [24]. The most common adverse events associated with peripheral nerve radiofrequency therapy are bleeding, local infection, tissue damage, and transient neuritis or neurological deficits, which are influenced by the thoroughness of preoperative assessment and expertise in puncture techniques [25]. Considering that both CRF and H-PRF can increase local temperature to approximately 80°C, they cause significant damage to pain receptors, thereby reducing pain and yielding a favorable therapeutic outcome. However, it should be noted that this elevated temperature may also induce numbness of the perineal skin in certain postoperative patients[26]. Compared with standard voltage PRF, the incidence of nerve numbness one year post-surgery was higher in the H-PRF group (25% vs 15%) [27]. Furthermore, the incidence of perineal nerve numbness in the group H-PRF at six months post-surgery was 27.5%, indicating that application of pulsed radiofrequency in high-voltage under long-term mode may result in tissue damage in peripheral nerve as a result of elevated electrode tip temperatures [28]. In our study, a 6-month follow-up revealed that the oral morphine equivalent and pregabalin dosage in the two patient groups did not show a significant decrease, which contrasts with the findings of SOUSA Correia J et al[6]. Instead, there was a daily increase in morphine equivalent over time. We hypothesize that these discrepancies may be attributed to the retrospective nature of the study conducted by SOUSA Correia J et al., which had a small sample size of 15 cases and a follow-up duration of only 3 months. Furthermore, the pain experienced with rectal cancer is of various types, with perineal neuralgia being just one aspect. It also includes invasive pain, inflammatory pain, and others. Real-world patients typically adhere to the WHO's three-step therapy for cancer pain, which involves utilizing potent opioids like morphine and adjunctive medications such as pregabalin for analgesia [29]. In conclusion, this study provides new insights regarding the clinical efficacy of two modes of CRF and H-PRF of the ganglion impar in the management of perineal pain in patients with advanced rectal cancer. Both treatment regimens could effectively control pain and improve the quality of life, with radiofrequency thermocoagulation showing superior long-term efficacy compared to high-voltage long-term pulsed radiofrequency. Declarations Disclosure statement The authors did not disclose any potential conflicts of interest. Funding This work was supported by Ziyang Medical Science Project (Grant No. KY2023035); Medical Research Project in Sichuan Province (Grant No. S21052); and Youth Science Foundation of Natural Science Foundation of Sichuan (Grant No. 2022NSFSC1346). Author Contribution Aimin Zhang and Qin Li were involved in the conception and study design.Bo Zhong and Hongwei Zhang were responsible for document retrieval. Qi Li and Huaiming Wang were involved in the writing and revision of the manuscript. Huaiming Wang, Qin Li, Taomei Zhang, Zhiqiang Wang, Ping Tao and Aimin Zhang were responsible for the data analysis. Hongwei Zhang and Aimin Zhang were in charge of concept design, article proofreading and project guidance. All authors were responsible for critical revision of the manuscript. 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PAIN AND THERAPY Acta Clin Croat 61: 103-108 Tables Table 1 Characteristics of the patients CRF (n=28) H-PRF (n=29) t/χ 2 -value P -value Age (years), mean±SD 68.9±6.9 70.3±7.1 -0.764 0.448 Sex, n (%) 0.147 0.186 Male 13 (46.4) 19 (65.5) Female 15 (53.6) 10 (34.5) Weight (kg), mean±SD 54.5±5.5 53.8±6.8 0.426 0.671 BMI (kg/m 2 ) 0.453 0.797 ＜18.5 7 (25.0) 8 (27.6) 18.5 ~ 24 12 (42.9) 14 (48.3) ＞24 9 (32.1) 7 (24.1) Pain duration (month) 1.233 0.540 ＜3 3 (10.7) 6 (20.7) 3 ~ 6 9 (32.1) 7 (24.1) ＞6 16 (57.2) 16 (55.2) Table 2 NRS, PHQ-9, PSQI and the time of keeping a sitting position of the studied groups CRF (n=28) H-PRF(n=29) t/χ 2 -value P -value NRS pre 6.54±1.95 6.81±1.42 -0.599 0.552 After 24 hours 4.33±0.37 ** 4.46±0.52 ** -1.084 0.283 After 1 week 2.41±0.46 ** 2.45±0.77 ** -0.237 0.814 After 1 month 1.55±0.41 ** 1.47±0.61 ** 0.579 0.565 After 3 months 2.56±0.67 ** 3.23±0.87 ** -3.249 0.002 After 6 months 2.98±0.72 ** 3.46±0.52 ** -2.893 0.005 Time effect F =455.156, P ＜0.001 Time and group interaction effects F =37.983, P ＜0.001 PHQ-9 pre 10.32±1.18 10.98±2.17 1.409 0.164 After 24 hours 6.24±1.86 ** 6.43±1.39 ** -0.438 0.663 After 1 week 7.22±2.01 ** 7.17±1.16 ** 0.116 0.908 After 1 month 7.48±1.95 ** 7.52±0.98 ** -0.098 0.992 After 3 months 8.03±1.43 ** 9.22±1.14 ** -3.480 0.001 After 6 months 8.09±1.88 ** 8.87±1.21 ** -2.588 0.012 Time effect F =152.5076, P ＜0.001 Time and group interaction effects F =19.798, P ＜0.001 PSQI pre 13.6±3.8 14.0±2.7 -0.459 0.648 After 24 hours 7.5±1.2 ** 7.8±1.7 ** -0.767 0.446 After 1 week 5.8±1.5 ** 6.2±0.9 ** -1.226 0.225 After 1 month 4.7±0.8 ** 5.1±1.2 ** -1.475 0.146 After 3 months 5.6±1.2 ** 8.5±2.4 ** -5.738 ＜0.001 After 6 months 7.1±1.9 ** 8.8±1.8 ** -4.469 0.001 Time effect F =193.478, P ＜0.001 Time and group interaction effects F =21.354, P ＜0.001 The time of keeping a sitting position pre 22.6±7.7 24.1±6.3 -0.798 0.428 After 24 hours 58.3±11.9 ** 55.6±8.1 ** 0.992 0.325 After 1 week 63.2±13.6 ** 63.5±11.3 ** -0.090 0.929 After 1 month 61.1±10.4 ** 62.8±17.4 ** -0.444 0.659 After 3 months 55.5±11.1 ** 48.8±7.5 ** 2.725 0.009 After 6 months 48.1±8.8 ** 40.9±7.2 ** -3.351 0.001 Time effect F =348.157, P ＜0.001 Time and group interaction effects F =41.159, P ＜0.001 Data are presented as mean ± SD, NRS = numerical rating scale. * P ＜0.05, ** P ＜0.01, *** P ＜0.001, compared to the baseline in each group. Table 3 Oral morphine equivalent and Pregabalin consumption of the studied groups CRF (n=28) H-PRF(n=29) t -value P -value Oral morphine equivalent (mg) pre 375.56±45.82 386.08±50.54 -0.822 0.414 After 6 months 486.81±55.42 *** 505.87±51.36 *** -1.347 0.183 Pregabalin consumption (mg) pre 340.32±51.18 351.85±62.17 -0.081 0.937 After 6 months 358.09±67.82 # 368.87±71.21 # -0.585 0.561 Data are presented as mean ± SD. * P ＜0.05, ** P ＜0.01, *** P ＜0.001, # P ＞0.05, compared to the baseline in each group. Table 4 The frequency of adverse events observed within the groups under investigation. CRF (n=28) H-PRF(n=29) χ 2 --value P -value bleeding 0 0 0 0 local infection, 0 0 0 0 rectal injury 0 0 0 0 perineal numbness After 24 hours 16 (57.1) 15 (51.7) 0.169 0.792 After 6 months 6 (21.4) ** 8 (27.5) 0.292 0.760 Additional Declarations No competing interests reported. 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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-4149738","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":284260979,"identity":"8ba54cd5-6f82-4d3e-ba9e-e78ff833a0b1","order_by":0,"name":"Qin Li","email":"","orcid":"","institution":"Sichuan Cancer Hospital \u0026 Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China","correspondingAuthor":false,"prefix":"","firstName":"Qin","middleName":"","lastName":"Li","suffix":""},{"id":284260981,"identity":"33f67064-e418-4371-af6a-a7c67fc385a2","order_by":1,"name":"Huaiming Wang","email":"","orcid":"","institution":"Sichuan Cancer Hospital \u0026 Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China","correspondingAuthor":false,"prefix":"","firstName":"Huaiming","middleName":"","lastName":"Wang","suffix":""},{"id":284260982,"identity":"c84c2d38-2edf-4444-ad96-86babc9e0b69","order_by":2,"name":"Bo Zhong","email":"","orcid":"","institution":"Yanjiang District People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Bo","middleName":"","lastName":"Zhong","suffix":""},{"id":284260983,"identity":"f23e52cb-2cb1-4959-8fb8-9e479eb4b823","order_by":3,"name":"Taomei Zhang","email":"","orcid":"","institution":"Yanjiang District People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Taomei","middleName":"","lastName":"Zhang","suffix":""},{"id":284260984,"identity":"bd7eb67b-263c-44ba-9c76-7554c501766b","order_by":4,"name":"Zhiqiang Wang","email":"","orcid":"","institution":"Yanjiang District People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Zhiqiang","middleName":"","lastName":"Wang","suffix":""},{"id":284260985,"identity":"28e8becd-b06b-4fbd-b17d-095d8f3cf31b","order_by":5,"name":"Ping Tao","email":"","orcid":"","institution":"Yanjiang District People's Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ping","middleName":"","lastName":"Tao","suffix":""},{"id":284260986,"identity":"b699d56f-cfd8-4acb-8625-a0f4c6e40197","order_by":6,"name":"Hongwei Zhang","email":"","orcid":"","institution":"Sichuan Cancer Hospital \u0026 Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China","correspondingAuthor":false,"prefix":"","firstName":"Hongwei","middleName":"","lastName":"Zhang","suffix":""},{"id":284260987,"identity":"ec23c7f1-41f8-4faf-81dc-50d618b9bc2f","order_by":7,"name":"Aimin Zhang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABBklEQVRIiWNgGAWjYDACCSjJxsB8AMSSIUULWwKIxUOsFrBiA+K0yM9ufvbwS41FNJ90z+cPP/7U8RjcSGB8XPGLQd4chxbGOcfMjWWOSeS2yZzdJtnbxgbSwmx4to/BcGcDdi3MEglm0hJsQC0SuduYGRt4QFrYJBt7GBIMDmDXwiaR/k1a4h9IS87jzwx/JAhr4ZHIMZP82AbWwiDNwGYA0dLwA7cWCYmcMmnGPpCWNDOgXxJ4JM88bDZsbJAw3IBDi/yM9G2SP77V5c6fkfwYFGJyfMeTDz5s+GMjj8sWcBCgxIXChcQGBsY2CVyqwYDxB4q9/SDT/+DVMQpGwSgYBSMLAAB8fVcq2yhSPgAAAABJRU5ErkJggg==","orcid":"","institution":"Sichuan Cancer Hospital \u0026 Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China","correspondingAuthor":true,"prefix":"","firstName":"Aimin","middleName":"","lastName":"Zhang","suffix":""}],"badges":[],"createdAt":"2024-03-22 12:29:37","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4149738/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4149738/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":53754447,"identity":"ec4a2082-cc49-4cf1-a194-1ccc28529c35","added_by":"auto","created_at":"2024-03-29 18:57:56","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":823667,"visible":true,"origin":"","legend":"\u003cp\u003eThe tip position of the needle was determined after the XperCT image reconstruction of DSA.\u003c/p\u003e\n\u003cp\u003e(Lateral view to clearly puncture the needle through the joint space of the first caudal vertebra，DSA-guided 3D scanning to determine that the tip of the needle was located anterior to the caudal vertebra and posterior to the rectum)\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4149738/v1/e6cab0682c12ba201714a842.png"},{"id":53754446,"identity":"fe8c3a12-2388-40a6-822c-a945141b5087","added_by":"auto","created_at":"2024-03-29 18:57:56","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":52277,"visible":true,"origin":"","legend":"\u003cp\u003eCONSORT flow diagram showing selection of study participants.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-4149738/v1/4bfd4fa1530169a52a7f7268.png"},{"id":55939217,"identity":"21b605e5-153c-46bc-85cd-e421c43e920c","added_by":"auto","created_at":"2024-05-06 14:42:06","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1336022,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4149738/v1/21aadb25-3745-48b3-9e1c-357f41a7809c.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Conventional versus high-voltage, long-term pulse Radiofrequency of ganglion impar in perineal pain with advanced rectal cancer: A Randomized, Double-Blind Controlled Trial","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePain is a prevalent symptom among patients with advanced diseases, with approximately 59% of patients undergoing cancer treatment, 64% of patients with advanced disease, and 33% of patients receiving curative treatment reporting pain\u0026nbsp;[1]. In addition, 10-20% of cancer patients may experience refractory cancer pain\u0026nbsp;[2]. Pain associated with advanced rectal cancer typically manifests in the perineum, abdomen, and lower back, with perineal pain being particularly pronounced. This discomfort significantly impacts the quality of life of patients\u0026nbsp;[3].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe ganglion impar is located anterior to the articulation of the sacrum and coccyx, and it is innervated by sympathetic and parasympathetic nerve fibers originating from the lumbosacral region. It modulates the transmission of signals related to nociceptive pain and sympathetic nerve pain in the perineum\u0026nbsp;[4].The ganglion impar (GIB), also known as Walters\u0026apos; block, is an easy and efficacious technique for targeting pelvic and perineal nociceptive pathways[5], GIB has demonstrated good efficacy in managing perineal pain\u0026nbsp;[6]. The clinical application of GIB has been extended to include drug blocking, chemical damage, and radiofrequency therapy [7]. Accumulating evidence indicates that Ganglion Impar Radiofrequency (RF) can alleviate cancer-related and non-cancer-related pain[8, 9].\u003c/p\u003e\n\u003cp\u003eThere are two modes of radiofrequency: conventional radiofrequency (CRF) and pulsed radiofrequency (PRF). CRF is safe and effective in treating sympathetic ganglia, whereas PRF exhibits limited therapeutic efficacy\u0026nbsp;[9]. Following the application of the ganglion impar high-voltage long-term pulsed radiofrequency (H-PRF) regimen, the remission rate of pudendal neuralgia remained high at 88.6% even after 3 months\u0026nbsp;[10], making it a promising strategy for the treatment of cancerous perineal pain\u0026nbsp;[8].\u0026nbsp;Nevertheless, few studies have directly compared the effectiveness of CRF versus H-PRF in the management of cancer-related perineal pain.\u003c/p\u003e\n\u003cp\u003eThe aim of this study was to evaluate the efficacy and safety of CRF and H-PRF of the ganglion impar in the management of perineal pain associated with advanced rectal cancer.\u003c/p\u003e"},{"header":"Methods ","content":"\u003cp\u003eStudy design and randomization\u003c/p\u003e\n\u003cp\u003eThis pilot study, conducted at the Department of Anesthesiology at Sichuan Cancer Hospital \u0026amp; Institute and Yanjiang District People\u0026apos;s Hospital, was a randomized, double-blind controlled trial registered with the Chinese Clinical Trial Registry (ChiCTR2200061800). The study was approved by the Medical Ethics Committee of the Ziyang People\u0026apos;s Hospital (KY-sj-2023-02) and all procedures were carried out in compliance with the Declaration of Helsinki. Prior to any procedures, written informed consent was obtained from the participants.\u003c/p\u003e\n\u003cp\u003eTo achieve a double-blind procedure, two physicians attended the participants at each center. One physician conducted assessments while the other managed randomization and device instructions. Subjects were informed about potential sensations during treatment and instructed not to disclose them to the assessing physician. A clinical nurse who was not involved in the process of designing the protocol, assigned randomization numbers and allocated 72 patients into either the group CRF or H-PRF at a 1:1 ratio. The treatment allocation was conducted in line with a predetermined randomization list generated using random blocks.\u003c/p\u003e\n\u003cp\u003eSubjects\u003c/p\u003e\n\u003cp\u003eBoth male and female patients attending the pain clinic were assessed to determine their eligibility and those that met the criteria were asked to participate in the study. The inclusion and exclusion criteria were assessed within the Department of Anesthesiology. \u003c/p\u003e\n\u003cp\u003eInclusion criteria:\u003c/p\u003e\n\u003cp\u003ePathologically confirmed diagnosis of rectal cancer,\u003c/p\u003e\n\u003cp\u003eCancerous pain with perineal pain, \u003c/p\u003e\n\u003cp\u003eIneffective perineal pain relief after oral opioid analgesics combined with pregabalin, willingness to accept invasive interventions, \u003c/p\u003e\n\u003cp\u003ePositive symptoms of the Grading System for Neuropathic Pain (GSNP) with a score of 3 or 4[11], \u003c/p\u003e\n\u003cp\u003eLife expectancy of at least 6 months, \u003c/p\u003e\n\u003cp\u003ePerineal pain with the following characteristics: (1) the pain was significantly Aggravated when sitting down, (2) the pain did not affect sleep at night, (3) the pain was not accompanied by objective sensory impairment, (4) the pain in the anal area was reduced after the diagnostic nerve block of the azygous ganglion.\u003c/p\u003e\n\u003cp\u003eExclusion criteria：\u003c/p\u003e\n\u003cp\u003eLumbosacral fracture or local anatomical variation that makes it difficult to puncture,\u003c/p\u003e\n\u003cp\u003eSystemic bacteremia or local infection at the puncture site,\u003c/p\u003e\n\u003cp\u003eThere are symptoms such as coagulation system diseases, diabetes, peptic ulcers, infections, and mental and psychological diseases,\u003c/p\u003e\n\u003cp\u003eDeveloped recent myocardial infarction, severe bradyarrhythmia, or heart block.\u003c/p\u003e\n\n\u003cp\u003eIntervention\u003c/p\u003e\n\u003cp\u003eOnce patients were admitted to undergo intervention surgery, standard indoor monitoring procedures were implemented. These procedures involved assessing the patient\u0026apos;s blood pressure, heart rate, respiration, pulse, and pulse oxygen saturation. The patient was then positioned in a prone position on the surgical treatment bed, and the disinfected following standard protocols. Next, the sacral and coccyx regions were visualized using oblique fluoroscopy to identify the needle insertion point, specifically the first coccyx joint space. Local anesthesia was administered prior to needle insertion under oblique fluoroscopy. With the assistance of digital subtraction angiography (DSA), the depth of the needle tip was ascertained using anteroposterior and lateral fluoroscopy. Finally, following the injection of 0.5ml of contrast agent and the reconstruction of the XperCT image, the needle tip was repositioned behind the rectum and in front of the anterior longitudinal ligament of the coccyx. (refer to Fig 1).\u003c/p\u003e\n\n\u003cp\u003eRadiofrequency electrode position test: Once the needle tip was determined, 50Hz, 0.1-0.6V stimulation was applied to induce discharge-like pain in the ganglionic innervation area, to achieve regular beating of perineal muscles at 2Hz and 0.5-2.0V, which confirmed successful targeting of the electrode position.\u003c/p\u003e\n\u003cp\u003ePatients in the group CRF underwent a continuous opening procedure starting at 50\u0026deg;C for 30 seconds, followed by 55\u0026deg;C for 30 seconds, with a gradual increase in temperature to 60\u0026deg;C-70\u0026deg;C for 60 seconds, 75\u0026deg;C for 120 seconds, and 80\u0026deg;C for 180 seconds. After surgery, approximately 4ml of 0.5% ropivacaine was administered to alleviate pain associated with local heat injury. In the H-PRF group, the radiofrequency instrument was re-configured to the manual pulse mode with specific parameters including a temperature of 42\u0026deg;C, frequency of 2 Hz, pulse duration of 20 ms, time duration of 900 s, and an initial pulsed RF field strength of 40 V which was incrementally raised to the maximum tolerable level by the patient (up to 100 V). The patient was monitored for 10 minutes post-treatment for abnormalities. Subsequently, they were returned to the ward where vital signs were also monitored using an electrocardiogram. The patient was instructed to lie on their back for 3 hours, and changes in lower limb blood flow were observed.\u003c/p\u003e\n\n\u003cp\u003eCollected Data\u003c/p\u003e\n\u003cp\u003eThe data collection and patient assessment were conducted by a well-trained pain physician who was blinded to the technique utilized. During subsequent visits, patients were prohibited from reviewing their previous data. \u003c/p\u003e\n\u003cp\u003eAssessments\u003c/p\u003e\n\u003cp\u003eThe patients were evaluated at multiple time intervals, including baseline (pre-surgery), 24 hours following surgery, 1 week after surgery, 1month post-surgery, 3 months post-surgery, and 6 months post-surgery. \u003c/p\u003e\n\u003cp\u003eThe demographic data collected included age, weight, Body Mass Index (BMI), duration of the pain procedure, initial numeric rating scales (NRS), GSNP, initial total daily dose of morphine and pregabalin, and duration of medication treatment.\u003c/p\u003e\n\u003cp\u003ea) Primary Outcome\u003c/p\u003e\n\u003cp\u003ePain intensity was evaluated using the Numerical Rating Scale (NRS), which ranged from 0 to 10. A 10 cm scale was employed to measure pain levels, with zero representing the absence of pain and 10 representing the most severe pain [12].\u003c/p\u003e\n\u003cp\u003eb) Secondary Outcome\u003c/p\u003e\n\u003cp\u003e1) The PHQ-9 self-rating scale was employed to evaluate the severity of depression, consisting of nine items. Despite its brevity, the scale demonstrated good reliability and validity. Scores ranging from 5 to 10 indicated mild depression, 10 to 15 indicated moderate depression, 15 to 20 indicated moderately severe depression, and scores exceeding 20 indicated severe depression [13].\u003c/p\u003e\n\u003cp\u003e2) The Pittsburgh Sleep Quality Index (PSQI) has been widely applied in the assessment of sleep quality among patients with sleep disorders and is commonly utilized to evaluate sleep patterns in individuals experiencing pain. Questionnaire data revealed that scores on the PSQI ranged from 0 to 5, indicating good sleep, 6 to 10 representing fair sleep, 11 to 15 indicating average sleep, and 16 to 21 corresponding to poor sleep [14].\u003c/p\u003e\n\u003cp\u003e3) The duration of maintaining a sitting position was recorded as the period within which a patient remained seated in a comfortable position until the onset of anal pain and the subsequent inability to maintain a seated position. These data were monitored by nurses during the patient\u0026apos;s hospital stay period, and family members were trained to perform accurate recording during the post-hospitalization follow-up period[15].\u003c/p\u003e\n\u003cp\u003e4) The opioid dosage administered preoperatively was quantified by converting it to morphine equivalent units, and the dosage of pregabalin was determined. The occurrence of anal numbness post-treatment, as well as any additional complications, was documented. \u003c/p\u003e\n\u003cp\u003eSample size calculation\u003c/p\u003e\n\u003cp\u003eDue to limited epidemiological data on the prevalence of rectal cancer presenting with perineal pain, this study was exploratory in nature and did not involve sample size calculations.\u003c/p\u003e\n\u003cp\u003eStatistics\u003c/p\u003e\n\u003cp\u003eSatistical analysis was performed using the SPSS 22.0 software (IBM, Beijing, China, 2017). Normally distributed continuous data were presented as mean \u0026plusmn; standard deviation (Mean \u0026plusmn; SD). Independent samples t-test was employed to compare two groups, while repeated measures ANOVA was conducted to compare multiple groups. Non-normally distributed continuous data were summarized using the median (M) and interquartile range (IQR). Group comparisons were conducted using the rank sum test, while count data were analyzed using the chi-square test or Fisher exact probability method. Rank data were compared using the rank sum test. A \u003cem\u003eP\u003c/em\u003e-value \u0026lt; 0.05 was considered to be statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003ePatent and Clinician Characteristics\u003c/p\u003e\n\u003cp\u003eInitially, 72 patients were screened at the Sichuan Cancer Hospital \u0026amp; Institute and Yanjiang District People\u0026apos;s Hospital. Among them, 12 individuals were excluded. Six cases were excluded due to failure to meet inclusion criteria, two cases due to the presence of heart block, and three cases due to sacrococcygeal area infection. Consequently, 60 patients were enrolled in the study, with three individuals withdrawn due to lack of follow-up resulting from mortality. Consequently, the final analysis included 57 patients, consisting of 32 males and 25 females within the cohort (Fig. 2), the patient characteristics are outlined in\u0026nbsp;Table 1.\u003c/p\u003e\n\u003cp\u003eEfficacy\u003c/p\u003e\n\u003cp\u003eThe NRS scores significantly decreased at the intervals of 24 hours, 1 week, 1 month, 3 months, and 6 months post-procedure compared to baseline in both groups (\u003cem\u003eP\u003c/em\u003e＜0.001). The NRS scores \u0026nbsp;were significantly lower at the 3-month (\u003cem\u003eP\u003c/em\u003e＜0.002) and 6-month (\u003cem\u003eP\u003c/em\u003e＜0.005) time points in group CRF compared to group H-PRF. Notably, there were no significant differences in pain levels between the two groups before the procedure, and at the 24-hour, 1-week, and 1-month follow-up assessments.\u0026nbsp;Table 2\u0026nbsp;shows that patients in group CRF had better analgesic outcomes compared to those in group H-PRF, as indicated by repeated measures analysis of variance (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.001).\u003c/p\u003e\n\u003cp\u003eOur results indicated that PHQ-9 scores were significantly decreased at the time intervals of 24 hours, 1 week, 1 month, 3 months and 6 months post-procedure compared to baseline in both groups (\u003cem\u003eP\u003c/em\u003e＜0.001). Moreover, significantly lowerPHQ-9 scores were recorded at the 3-month (\u003cem\u003eP\u003c/em\u003e＜0.001) and 6-month (\u003cem\u003eP\u003c/em\u003e＜0.012) time points in group CRF compared to group H-PRF. There were no significant differences in depression levels between the two cohorts before the intervention, as well as during the 24-hour, 1-week, and 1-month post-procedure, as depicted in\u0026nbsp;Table 2.\u003c/p\u003e\n\u003cp\u003ePatients in both groups exhibited enhanced sleep quality as lower pain levels, indicated by a decrease in PSQI scores starting 24 hours post-surgery and reaching their lowest point 1-month post-surgery before gradually increasing. Moreover, both groups demonstrated a significant reduction in PSQI scores at all postoperative time points compared to preoperative scores (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.05). Further analysis found no statistically significant differences in PSQI scores between the two groups at 24 hours, 1 week, and 1month post-procedure (\u003cem\u003eP\u003c/em\u003e\u0026gt;0.05). However, the PSQI score of the group H-PRF was significantly higher compared with that of group CRF at 3 months and 6 months post-procedure following the operation (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.05), as showed in\u0026nbsp;Table 2.\u003c/p\u003e\n\u003cp\u003eAfter receiving treatment, the duration of time spent in a seated position by two groups of patients initially increased within 24 hours post-surgery, reached its highest point at 1-week post-surgery, and then gradually decreased. The study found significantly lower sitting-position measurements at both the 3-month (P \u0026lt; 0.009) and 6-month \u0026nbsp;(P \u0026lt; 0.001) time points in group CRF compared to group H-PRF. \u0026nbsp;Prior to the procedure, as well as at the 24-hour, 1-week, and 1-month follow-up assessments, there were no significant differences in the duration of time spent in a seated position between the two groups (\u003cem\u003eP\u003c/em\u003e＞0.05), as showed in\u0026nbsp;Table 2.\u003c/p\u003e\n\u003cp\u003eOral morphine equivalent and Pregabalin consumption\u003c/p\u003e\n\u003cp\u003ePatients in both groups experienced rectal and perineal pain, a common consequence of rectal cancer. While radiofrequency therapy successfully reduced perineal pain, oral medications, especially morphine, were still necessary to manage pain in other areas caused by the cancer. Analysis of data shown in\u0026nbsp;Table 3\u0026nbsp;showed no significant differences (\u003cem\u003eP\u003c/em\u003e\u0026gt;0.05) in daily oral morphine equivalent and pregabalin dosage between the two patient groups before and 6 months post-surgery.\u003c/p\u003e\n\u003cp\u003eSafety\u003c/p\u003e\n\u003cp\u003eTable 4 indicate that neither group of patients experienced adverse events such as significant bleeding at the puncture site, local infection, or rectal injury. Primary postoperative side effect observed was numbness in the perineum. In the CRF group, 16 cases (57.1%) reported perineal numbness 24 hours postoperatively, with 6 cases (21.4%) demonstrating persistent symptoms at the 6-month follow-up. Similarly, in the H-PRF group, numbness was reported by 15 cases (51.6%) at the 24-hour mark, with 8 cases (27.5%) still experiencing unresolved symptoms at the 6-month assessment. .\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, we adopted a double-center, randomized, active-controlled, double-blind clinical trial design to investigate the safety and efficacy of CRF and H-PRF in the treatment of perineal pain and improvement of quality of life in patients with advanced rectal cancer by targeting the ganglion impar. The results demonstrated that the long-term effectiveness of CRF exceeded that of H-PRF.\u003c/p\u003e\n\n\u003cp\u003eOccurrence of primary perineal pain has been linked to sympathetic sensory coupling, and the ganglion impar is the distal ganglion of the sympathetic chain [16]. Bocking the ganglion impar can significantly alleviate perineal pain and decrease the need for opioid analgesics [6]. Radiofrequency therapy is an effective technique for the management of ganglion impar. Radiofrequency pain treatment can be categorized into two modes: continuous radiofrequency ablation (CRF) and pulsed radiofrequency (PRF)[17]. Previous studies showed that patients experiencing primary perineal pain can experience a significant reduction in pain over a 6-month monitoring period following treatment with pulsed radiofrequency in the ganglion impar [18]. Nicholas A Zacharias et al. found that PRF and CRF can alleviate sympathetic nerve-mediated pain, including the ganglion impar. Notably, CRF showed better long-term effects in controlling noncancerous perineal pain [19]. In addition, PRF combined with plexus chemical destruction can achieve long-term pain control [20]. The aforementioned studies demonstrate that PRF is still not ideal for long-term relief of perineal pain.\u003c/p\u003e\n\n\u003cp\u003eHigh-voltage pulsed radiofrequency (H-PRF) has a pronounced neuromodulatory effect by generating a robust electric field [8]. Furthermore, H-PRF demonstrates a lasting thermal damage effect, although significantly less pronounced than that observed with CRF techniques. Consequently, H-PRF is an innovative PRF modality that exhibits partial continuous thermal effects and a high-voltage, high-field-strength electric field [21, 22]. Cheng-Long Wang et al. found that H-PRF provided pain relief lasting beyond 12 weeks in individuals diagnosed with pudendal neuralgia, concurrently enhancing mood and overall quality of life [10]. The above results offer compelling evidence confirming that H-PRF treatment yielded significant analgesic effects, alleviated depression, enhanced sitting time, and improved sleep quality in group H-PRF at the six-month follow-up period. In addition, the analgesic efficacy of the H-PRF group was significantly poor compared with that of the CRF group at the 3-month follow-up. This difference may stem from the more precise ablation of the dorsal root ganglion sensory nerve by CRF [23], along with the observation that the duration of pain relief for neuropathic pain with H-PRF using the PRF mode persisted for 3 months [24].\u003c/p\u003e\n\n\u003cp\u003eThe most common adverse events associated with peripheral nerve radiofrequency therapy are bleeding, local infection, tissue damage, and transient neuritis or neurological deficits, which are influenced by the thoroughness of preoperative assessment and expertise in puncture techniques [25]. Considering that both CRF and H-PRF can increase local temperature to approximately 80\u0026deg;C, they cause significant damage to pain receptors, thereby reducing pain and yielding a favorable therapeutic outcome. However, it should be noted that this elevated temperature may also induce numbness of the perineal skin in certain postoperative patients[26]. Compared with standard voltage PRF, the incidence of nerve numbness one year post-surgery was higher in the H-PRF group (25% vs 15%) [27]. Furthermore, the incidence of perineal nerve numbness in the group H-PRF at six months post-surgery was 27.5%, indicating that application of pulsed radiofrequency in high-voltage under long-term mode may result in tissue damage in peripheral nerve as a result of elevated electrode tip temperatures [28].\u003c/p\u003e\n\n\u003cp\u003eIn our study, a 6-month follow-up revealed that the oral morphine equivalent and pregabalin dosage in the two patient groups did not show a significant decrease, which contrasts with the findings of SOUSA Correia J et al[6]. Instead, there was a daily increase in morphine equivalent over time. We hypothesize that these discrepancies may be attributed to the retrospective nature of the study conducted by SOUSA Correia J et al., which had a small sample size of 15 cases and a follow-up duration of only 3 months.\u003c/p\u003e\n\n\u003cp\u003eFurthermore, the pain experienced with rectal cancer is of various types, with perineal neuralgia being just one aspect. It also includes invasive pain, inflammatory pain, and others. Real-world patients typically adhere to the WHO\u0026apos;s three-step therapy for cancer pain, which involves utilizing potent opioids like morphine and adjunctive medications such as pregabalin for analgesia [29].\u003c/p\u003e\n\u003cp\u003eIn conclusion, this study provides new insights regarding the clinical efficacy of two modes of CRF and H-PRF of the ganglion impar in the management of perineal pain in patients with advanced rectal cancer. Both treatment regimens could effectively control pain and improve the quality of life, with radiofrequency thermocoagulation showing superior long-term efficacy compared to high-voltage long-term pulsed radiofrequency.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eDisclosure statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors did not disclose any potential conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by Ziyang Medical Science Project (Grant No. KY2023035); Medical Research Project in Sichuan Province (Grant No. S21052); and Youth Science Foundation of Natural Science Foundation of Sichuan (Grant No. 2022NSFSC1346).\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eAimin Zhang and Qin Li were involved in the conception and study design.Bo Zhong and Hongwei Zhang were responsible for document retrieval. Qi Li and Huaiming Wang were involved in the writing and revision of the manuscript. Huaiming Wang, Qin Li, Taomei Zhang, Zhiqiang Wang, Ping Tao and Aimin Zhang were responsible for the data analysis. Hongwei Zhang and Aimin Zhang were in charge of concept design, article proofreading and project guidance. All authors were responsible for critical revision of the manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003evan den Beuken-van Everdingen M, de Rijke J, Kessels A (2007) Prevalence of pain in patients with cancer: a systematic review of the past 40 years Ann Oncol 18: 1437-1449\u003c/li\u003e\n\u003cli\u003eMercadante S (2023) Refractory Cancer Pain and Intrathecal Therapy: Critical Review of a Systematic Review Pain Ther 12: 645-654\u003c/li\u003e\n\u003cli\u003eLee JY, Kim HC, Huh JW, Sim WS, Lim HY, Lee EK, Park HG, Bang YJ (2017) Incidence and risk factors for rectal pain after laparoscopic rectal cancer surgery J Int Med Res 45: 781-791\u003c/li\u003e\n\u003cli\u003eFranco JVA, Tarek T, Hung JJ, Yu-Tian X, Stanislav I, Virginia G, Valeria V (2018) Non-pharmacological interventions for treating chronic prostatitis/chronic pelvic pain syndrome: a Cochrane systematic review Bju International \u003c/li\u003e\n\u003cli\u003eNalini KB, Shivanna S, Vishnu MS, Mohan CVR (2018) Transcoccygeal neurolytic ganglion impar block for perineal pain: A case series J Anaesthesiol Clin Pharmacol 34: 544-547\u003c/li\u003e\n\u003cli\u003eSousa Correia J, Silva M, Castro C, Miranda L, Agrelo A (2019) The efficacy of the ganglion impar block in perineal and pelvic cancer pain Support Care Cancer 27: 4327-4330\u003c/li\u003e\n\u003cli\u003eChoudhary R, Kunal K, Kumar D, Nagaraju V, Verma S (2021) Improvement in Pain Following Ganglion Impar Blocks and Radiofrequency Ablation in Coccygodynia Patients: A Systematic Review Rev Bras Ortop (Sao Paulo) 56: 558-566\u003c/li\u003e\n\u003cli\u003eG\u0026uuml;rses E (2014) Impar ganglion radiofrequency application in successful management of oncologic perineal pain J Pak Med Assoc 64: 697-699\u003c/li\u003e\n\u003cli\u003eUsmani H, Dureja GP, Andleeb R, Tauheed N, Asif N (2018) Conventional Radiofrequency Thermocoagulation vs Pulsed Radiofrequency Neuromodulation of Ganglion Impar in Chronic Perineal Pain of Nononcological Origin Pain Med 19: 2348-2356\u003c/li\u003e\n\u003cli\u003eWang CL, Song T (2022) The Clinical Efficacy of High-Voltage Long-Duration Pulsed Radiofrequency Treatment in Pudendal Neuralgia: A Retrospective Study Neuromodulation 25: 1372-1377\u003c/li\u003e\n\u003cli\u003eAbbas DN, Reyad RM (2018) Thermal Versus Super Voltage Pulsed Radiofrequency of Stellate Ganglion in Post-Mastectomy Neuropathic Pain Syndrome: A Prospective Randomized Trial Pain Physician 21: 351-362\u003c/li\u003e\n\u003cli\u003eZeng X, Zhu J, Li J, Chen C, Sang L, Liu M, Song L, Liu H (2024) Patient Controlled Subcutaneous Analgesia of Hydromorphone Versus Morphine to Treat Moderate and Severe Cancer Pain: A Randomized Double-Blind Controlled Trial J Pain Symptom Manage 67: 50-58\u003c/li\u003e\n\u003cli\u003eTucker DR, Noga HL, Lee C, Chiu DS, Bedaiwy MA, Williams C, Allaire C, Talhouk A, Yong PJ (2023) Pelvic pain comorbidities associated with quality of life after endometriosis surgery Am J Obstet Gynecol 229: 147.e141-147.e120\u003c/li\u003e\n\u003cli\u003eKirmizigil B, Demiralp C (2020) Effectiveness of functional exercises on pain and sleep quality in patients with primary dysmenorrhea: a randomized clinical trial Arch Gynecol Obstet 302: 153-163\u003c/li\u003e\n\u003cli\u003eHibner M, Castellanos ME, Drachman D, Balducci J (2012) Repeat operation for treatment of persistent pudendal nerve entrapment after pudendal neurolysis J Minim Invasive Gynecol 19: 325-330\u003c/li\u003e\n\u003cli\u003eLevesque A, Riant T, Ploteau S, Rigaud J, Labat JJ (2018) Clinical Criteria of Central Sensitization in Chronic Pelvic and Perineal Pain (Convergences PP Criteria): Elaboration of a Clinical Evaluation Tool Based on Formal Expert Consensus Pain Med 19: 2009-2015\u003c/li\u003e\n\u003cli\u003eWalsh T, Malhotra R, Sharma M (2022) Radiofrequency techniques for chronic pain BJA Educ 22: 474-483\u003c/li\u003e\n\u003cli\u003eLi SQ, Jiang L, Cui LG, Jia DL (2021) Clinical efficacy of ultrasound-guided pulsed radiofrequency combined with ganglion impar block for treatment of perineal pain World J Clin Cases 9: 2153-2159\u003c/li\u003e\n\u003cli\u003eZacharias NA, Karri J, Garcia C, Lachman LK, Abd-Elsayed A (2021) Interventional Radiofrequency Treatment for the Sympathetic Nervous System: A Review Article Pain Ther 10: 115-141\u003c/li\u003e\n\u003cli\u003eHetta DF, Mohamed AA, Abdel Eman RM, Abd El Aal FA, Helal ME (2020) Pulsed Radiofrequency of the Sacral Roots Improves the Success Rate of Superior Hypogastric Plexus Neurolysis in Controlling Pelvic and Perineal Cancer Pain Pain Physician 23: 149-157\u003c/li\u003e\n\u003cli\u003eLuo F, Wang T, Shen Y, Meng L, Lu J, Ji N (2017) High Voltage Pulsed Radiofrequency for the Treatment of Refractory Neuralgia of the Infraorbital Nerve: A Prospective Double-Blinded Randomized Controlled Study Pain Physician 20: 271-279\u003c/li\u003e\n\u003cli\u003eLi L, Liu X, Liu Y, Liu T, Zhang Z (2024) Efficacy of high-voltage, long-duration pulsed radiofrequency for the treatment of acute herpes zoster-related trigeminal neuralgia in a patient with permanent pacemaker The Korean journal of pain \u003c/li\u003e\n\u003cli\u003eDemircay E, Kabatas S, Cansever T, Yilmaz C, Tuncay C, Altinors N (2010) Radiofrequency thermocoagulation of ganglion impar in the management of coccydynia: preliminary results Turk Neurosurg 20: 328-333\u003c/li\u003e\n\u003cli\u003eChalermkitpanit P, Pannangpetch P, Kositworakitkun Y, Singhatanadgige W, Yingsakmongkol W, Pasuhirunnikorn P, Tanasansomboon T (2023) Ultrasound-guided pulsed radiofrequency of cervical nerve root for cervical radicular pain: a prospective randomized controlled trial Spine J 23: 651-655\u003c/li\u003e\n\u003cli\u003ePastrak M, Visnjevac O, Visnjevac T, Ma F, Abd-Elsayed A (2022) Safety of Conventional and Pulsed Radiofrequency Lesions of the Dorsal Root Entry Zone Complex (DREZC) for Interventional Pain Management: A Systematic Review Pain Ther 11: 411-445\u003c/li\u003e\n\u003cli\u003eWang CH, Dou Z, Yan MW, Tang YZ, Zhao R, Han YJ, Ni JX (2021) The comparison of efficacy and complications of coblation and radiofrequency thermocoagulation for V2/V3 idiopathic trigeminal neuralgia: a retrospective cohort study of 292 cases BMC Anesthesiol 21: 9\u003c/li\u003e\n\u003cli\u003eXin-Ze Z, Lan M, Ying S, Fang L, Stomatology DO, Hospital BT, University CM, Pain DO, Hospital BT, University CM (2017) CLINICAL EVALUATION OF HIGH VOLTAGE PULSED RADIOFREQUENCY FOR TREATMENT OF PATIENTS WITH REFRACTORY NEURALGIA OF INFRAORBITAL NERVE Chinese Journal of Pain Medicine \u003c/li\u003e\n\u003cli\u003eLuo F, Wang T, Shen Y, Meng L, Lu JJ, Ji N (2017) High Voltage Pulsed Radiofrequency for the Treatment of Refractory Neuralgia of the Infraorbital Nerve: A Prospective Double-Blinded Randomized Controlled Study Pain Physician 20: 271-279\u003c/li\u003e\n\u003cli\u003eBrozović G, Lesar N, Janev D, Bo\u0026scaron;njak T, Muhaxhiri B (2022) CANCER PAIN AND THERAPY Acta Clin Croat 61: 103-108\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1 Characteristics of the patients\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.54954954954955%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.072072072072071%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.135135135135135%\" valign=\"top\"\u003e\n \u003cp\u003eCRF\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;(n=28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.135135135135135%\" valign=\"top\"\u003e\n \u003cp\u003eH-PRF\u003c/p\u003e\n \u003cp\u003e(n=29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.054054054054054%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003et/\u0026chi;\u003csup\u003e2\u003c/sup\u003e\u003c/em\u003e-value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.054054054054054%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.54954954954955%\" valign=\"top\"\u003e\n \u003cp\u003eAge (years), mean\u0026plusmn;SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.072072072072071%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.135135135135135%\" valign=\"top\"\u003e\n \u003cp\u003e68.9\u0026plusmn;6.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.135135135135135%\" valign=\"top\"\u003e\n \u003cp\u003e70.3\u0026plusmn;7.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.054054054054054%\" valign=\"top\"\u003e\n \u003cp\u003e-0.764\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.054054054054054%\" valign=\"top\"\u003e\n \u003cp\u003e0.448\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.54954954954955%\" valign=\"top\"\u003e\n \u003cp\u003eSex, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.072072072072071%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.135135135135135%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.135135135135135%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.054054054054054%\" valign=\"top\"\u003e\n \u003cp\u003e0.147\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.054054054054054%\" valign=\"top\"\u003e\n \u003cp\u003e0.186\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.54954954954955%\" valign=\"top\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.072072072072071%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.135135135135135%\" valign=\"top\"\u003e\n \u003cp\u003e13 (46.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.135135135135135%\" valign=\"top\"\u003e\n \u003cp\u003e19 (65.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.054054054054054%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.054054054054054%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.54954954954955%\" valign=\"top\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.072072072072071%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.135135135135135%\" valign=\"top\"\u003e\n \u003cp\u003e15 (53.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.135135135135135%\" valign=\"top\"\u003e\n \u003cp\u003e10 (34.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.054054054054054%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.054054054054054%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.54954954954955%\" valign=\"top\"\u003e\n \u003cp\u003eWeight (kg), mean\u0026plusmn;SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.072072072072071%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.135135135135135%\" valign=\"top\"\u003e\n \u003cp\u003e54.5\u0026plusmn;5.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.135135135135135%\" valign=\"top\"\u003e\n \u003cp\u003e53.8\u0026plusmn;6.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.054054054054054%\" valign=\"top\"\u003e\n \u003cp\u003e0.426\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.054054054054054%\" valign=\"top\"\u003e\n \u003cp\u003e0.671\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.54954954954955%\" valign=\"top\"\u003e\n \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.072072072072071%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.135135135135135%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.135135135135135%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.054054054054054%\" valign=\"top\"\u003e\n \u003cp\u003e0.453\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.054054054054054%\" valign=\"top\"\u003e\n \u003cp\u003e0.797\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.54954954954955%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; ＜18.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.072072072072071%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.135135135135135%\" valign=\"top\"\u003e\n \u003cp\u003e7 (25.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.135135135135135%\" valign=\"top\"\u003e\n \u003cp\u003e8 (27.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.054054054054054%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.054054054054054%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.54954954954955%\" valign=\"top\"\u003e\n \u003cp\u003e18.5 ~ 24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.072072072072071%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.135135135135135%\" valign=\"top\"\u003e\n \u003cp\u003e12 (42.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.135135135135135%\" valign=\"top\"\u003e\n \u003cp\u003e14 (48.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.054054054054054%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.054054054054054%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.54954954954955%\" valign=\"top\"\u003e\n \u003cp\u003e＞24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.072072072072071%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.135135135135135%\" valign=\"top\"\u003e\n \u003cp\u003e9 (32.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.135135135135135%\" valign=\"top\"\u003e\n \u003cp\u003e7 (24.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.054054054054054%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.054054054054054%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.54954954954955%\" valign=\"top\"\u003e\n \u003cp\u003ePain duration (month)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.072072072072071%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.135135135135135%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.135135135135135%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.054054054054054%\" valign=\"top\"\u003e\n \u003cp\u003e1.233\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.054054054054054%\" valign=\"top\"\u003e\n \u003cp\u003e0.540\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.54954954954955%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; ＜3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.072072072072071%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.135135135135135%\" valign=\"top\"\u003e\n \u003cp\u003e3 (10.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.135135135135135%\" valign=\"top\"\u003e\n \u003cp\u003e6 (20.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.054054054054054%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.054054054054054%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.54954954954955%\" valign=\"top\"\u003e\n \u003cp\u003e3 ~ 6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.072072072072071%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.135135135135135%\" valign=\"top\"\u003e\n \u003cp\u003e9 (32.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.135135135135135%\" valign=\"top\"\u003e\n \u003cp\u003e7 (24.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.054054054054054%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.054054054054054%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.54954954954955%\" valign=\"top\"\u003e\n \u003cp\u003e＞6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.072072072072071%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.135135135135135%\" valign=\"top\"\u003e\n \u003cp\u003e16 (57.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.135135135135135%\" valign=\"top\"\u003e\n \u003cp\u003e16 (55.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.054054054054054%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.054054054054054%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 2 NRS, PHQ-9, PSQI and the time of keeping a sitting position of the studied groups\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.869801084990957%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.24231464737794%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eCRF (n=28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.24231464737794%\" valign=\"top\"\u003e\n \u003cp\u003eH-PRF(n=29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.370705244122966%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003et/\u0026chi;\u003csup\u003e2\u003c/sup\u003e\u003c/em\u003e-value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.2748643761302%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"6\" valign=\"top\"\u003e\n \u003cp\u003eNRS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.869801084990957%\" valign=\"top\"\u003e\n \u003cp\u003epre\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.24231464737794%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e6.54\u0026plusmn;1.95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.24231464737794%\" valign=\"top\"\u003e\n \u003cp\u003e6.81\u0026plusmn;1.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.370705244122966%\" valign=\"top\"\u003e\n \u003cp\u003e-0.599\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.2748643761302%\" valign=\"top\"\u003e\n \u003cp\u003e0.552\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.869801084990957%\" valign=\"top\"\u003e\n \u003cp\u003eAfter 24 hours\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.24231464737794%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e4.33\u0026plusmn;0.37\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.24231464737794%\" valign=\"top\"\u003e\n \u003cp\u003e4.46\u0026plusmn;0.52\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.370705244122966%\" valign=\"top\"\u003e\n \u003cp\u003e-1.084\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.2748643761302%\" valign=\"top\"\u003e\n \u003cp\u003e0.283\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.869801084990957%\" valign=\"top\"\u003e\n \u003cp\u003eAfter 1 week\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.24231464737794%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e2.41\u0026plusmn;0.46\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.24231464737794%\" valign=\"top\"\u003e\n \u003cp\u003e2.45\u0026plusmn;0.77\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.370705244122966%\" valign=\"top\"\u003e\n \u003cp\u003e-0.237\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.2748643761302%\" valign=\"top\"\u003e\n \u003cp\u003e0.814\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.869801084990957%\" valign=\"top\"\u003e\n \u003cp\u003eAfter 1 month\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.24231464737794%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e1.55\u0026plusmn;0.41\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.24231464737794%\" valign=\"top\"\u003e\n \u003cp\u003e1.47\u0026plusmn;0.61\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.370705244122966%\" valign=\"top\"\u003e\n \u003cp\u003e0.579\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.2748643761302%\" valign=\"top\"\u003e\n \u003cp\u003e0.565\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.869801084990957%\" valign=\"top\"\u003e\n \u003cp\u003eAfter 3 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.24231464737794%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e2.56\u0026plusmn;0.67\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.24231464737794%\" valign=\"top\"\u003e\n \u003cp\u003e3.23\u0026plusmn;0.87\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.370705244122966%\" valign=\"top\"\u003e\n \u003cp\u003e-3.249\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.2748643761302%\" valign=\"top\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.869801084990957%\" valign=\"top\"\u003e\n \u003cp\u003eAfter 6 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.24231464737794%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e2.98\u0026plusmn;0.72\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.24231464737794%\" valign=\"top\"\u003e\n \u003cp\u003e3.46\u0026plusmn;0.52\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.370705244122966%\" valign=\"top\"\u003e\n \u003cp\u003e-2.893\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.2748643761302%\" valign=\"top\"\u003e\n \u003cp\u003e0.005\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"68.35443037974683%\" colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003eTime effect\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.645569620253166%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eF\u003c/em\u003e=455.156, \u003cem\u003eP\u003c/em\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"68.35443037974683%\" colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003eTime and group interaction effects\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.645569620253166%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eF\u003c/em\u003e=37.983, \u003cem\u003eP\u003c/em\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"6\" valign=\"top\"\u003e\n \u003cp\u003ePHQ-9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.869801084990957%\" valign=\"top\"\u003e\n \u003cp\u003epre\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.24231464737794%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e10.32\u0026plusmn;1.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.24231464737794%\" valign=\"top\"\u003e\n \u003cp\u003e10.98\u0026plusmn;2.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.370705244122966%\" valign=\"top\"\u003e\n \u003cp\u003e1.409\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.2748643761302%\" valign=\"top\"\u003e\n \u003cp\u003e0.164\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.869801084990957%\" valign=\"top\"\u003e\n \u003cp\u003eAfter 24 hours\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.24231464737794%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e6.24\u0026plusmn;1.86\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.24231464737794%\" valign=\"top\"\u003e\n \u003cp\u003e6.43\u0026plusmn;1.39\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.370705244122966%\" valign=\"top\"\u003e\n \u003cp\u003e-0.438\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.2748643761302%\" valign=\"top\"\u003e\n \u003cp\u003e0.663\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.869801084990957%\" valign=\"top\"\u003e\n \u003cp\u003eAfter 1 week\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.24231464737794%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e7.22\u0026plusmn;2.01\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.24231464737794%\" valign=\"top\"\u003e\n \u003cp\u003e7.17\u0026plusmn;1.16\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.370705244122966%\" valign=\"top\"\u003e\n \u003cp\u003e0.116\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.2748643761302%\" valign=\"top\"\u003e\n \u003cp\u003e0.908\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.869801084990957%\" valign=\"top\"\u003e\n \u003cp\u003eAfter 1 month\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.24231464737794%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e7.48\u0026plusmn;1.95\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.24231464737794%\" valign=\"top\"\u003e\n \u003cp\u003e7.52\u0026plusmn;0.98\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.370705244122966%\" valign=\"top\"\u003e\n \u003cp\u003e-0.098\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.2748643761302%\" valign=\"top\"\u003e\n \u003cp\u003e0.992\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.869801084990957%\" valign=\"top\"\u003e\n \u003cp\u003eAfter 3 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.24231464737794%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e8.03\u0026plusmn;1.43\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.24231464737794%\" valign=\"top\"\u003e\n \u003cp\u003e9.22\u0026plusmn;1.14\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.370705244122966%\" valign=\"top\"\u003e\n \u003cp\u003e-3.480\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.2748643761302%\" valign=\"top\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.869801084990957%\" valign=\"top\"\u003e\n \u003cp\u003eAfter 6 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.24231464737794%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e8.09\u0026plusmn;1.88\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.24231464737794%\" valign=\"top\"\u003e\n \u003cp\u003e8.87\u0026plusmn;1.21\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.370705244122966%\" valign=\"top\"\u003e\n \u003cp\u003e-2.588\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.2748643761302%\" valign=\"top\"\u003e\n \u003cp\u003e0.012\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"68.35443037974683%\" colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003eTime effect\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.645569620253166%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eF\u003c/em\u003e=152.5076, \u003cem\u003eP\u003c/em\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"68.35443037974683%\" colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003eTime and group interaction effects\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.645569620253166%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eF\u003c/em\u003e=19.798, \u003cem\u003eP\u003c/em\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"6\" valign=\"top\"\u003e\n \u003cp\u003ePSQI\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.869801084990957%\" valign=\"top\"\u003e\n \u003cp\u003epre\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.24231464737794%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e13.6\u0026plusmn;3.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.24231464737794%\" valign=\"top\"\u003e\n \u003cp\u003e14.0\u0026plusmn;2.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.370705244122966%\" valign=\"top\"\u003e\n \u003cp\u003e-0.459\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.2748643761302%\" valign=\"top\"\u003e\n \u003cp\u003e0.648\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.869801084990957%\" valign=\"top\"\u003e\n \u003cp\u003eAfter 24 hours\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.24231464737794%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e7.5\u0026plusmn;1.2\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.24231464737794%\" valign=\"top\"\u003e\n \u003cp\u003e7.8\u0026plusmn;1.7\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.370705244122966%\" valign=\"top\"\u003e\n \u003cp\u003e-0.767\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.2748643761302%\" valign=\"top\"\u003e\n \u003cp\u003e0.446\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.869801084990957%\" valign=\"top\"\u003e\n \u003cp\u003eAfter 1 week\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.24231464737794%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e5.8\u0026plusmn;1.5\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.24231464737794%\" valign=\"top\"\u003e\n \u003cp\u003e6.2\u0026plusmn;0.9\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.370705244122966%\" valign=\"top\"\u003e\n \u003cp\u003e-1.226\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.2748643761302%\" valign=\"top\"\u003e\n \u003cp\u003e0.225\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.869801084990957%\" valign=\"top\"\u003e\n \u003cp\u003eAfter 1 month\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.24231464737794%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e4.7\u0026plusmn;0.8\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.24231464737794%\" valign=\"top\"\u003e\n \u003cp\u003e5.1\u0026plusmn;1.2\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.370705244122966%\" valign=\"top\"\u003e\n \u003cp\u003e-1.475\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.2748643761302%\" valign=\"top\"\u003e\n \u003cp\u003e0.146\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.869801084990957%\" valign=\"top\"\u003e\n \u003cp\u003eAfter 3 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.24231464737794%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e5.6\u0026plusmn;1.2\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.24231464737794%\" valign=\"top\"\u003e\n \u003cp\u003e8.5\u0026plusmn;2.4\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.370705244122966%\" valign=\"top\"\u003e\n \u003cp\u003e-5.738\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.2748643761302%\" valign=\"top\"\u003e\n \u003cp\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.869801084990957%\" valign=\"top\"\u003e\n \u003cp\u003eAfter 6 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.24231464737794%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e7.1\u0026plusmn;1.9\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.24231464737794%\" valign=\"top\"\u003e\n \u003cp\u003e8.8\u0026plusmn;1.8\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.370705244122966%\" valign=\"top\"\u003e\n \u003cp\u003e-4.469\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.2748643761302%\" valign=\"top\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"68.35443037974683%\" colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003eTime effect\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.645569620253166%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eF\u003c/em\u003e=193.478, \u003cem\u003eP\u003c/em\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"68.35443037974683%\" colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003eTime and group interaction effects\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.645569620253166%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eF\u003c/em\u003e=21.354, \u003cem\u003eP\u003c/em\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"6\" valign=\"top\"\u003e\n \u003cp\u003eThe time of keeping a sitting position\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.678119349005424%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003epre\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.43399638336347%\" valign=\"top\"\u003e\n \u003cp\u003e22.6\u0026plusmn;7.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.24231464737794%\" valign=\"top\"\u003e\n \u003cp\u003e24.1\u0026plusmn;6.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.370705244122966%\" valign=\"top\"\u003e\n \u003cp\u003e-0.798\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.2748643761302%\" valign=\"top\"\u003e\n \u003cp\u003e0.428\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.678119349005424%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eAfter 24 hours\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.43399638336347%\" valign=\"top\"\u003e\n \u003cp\u003e58.3\u0026plusmn;11.9\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.24231464737794%\" valign=\"top\"\u003e\n \u003cp\u003e55.6\u0026plusmn;8.1\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.370705244122966%\" valign=\"top\"\u003e\n \u003cp\u003e0.992\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.2748643761302%\" valign=\"top\"\u003e\n \u003cp\u003e0.325\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.678119349005424%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eAfter 1 week\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.43399638336347%\" valign=\"top\"\u003e\n \u003cp\u003e63.2\u0026plusmn;13.6\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.24231464737794%\" valign=\"top\"\u003e\n \u003cp\u003e63.5\u0026plusmn;11.3\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.370705244122966%\" valign=\"top\"\u003e\n \u003cp\u003e-0.090\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.2748643761302%\" valign=\"top\"\u003e\n \u003cp\u003e0.929\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.678119349005424%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eAfter 1 month\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.43399638336347%\" valign=\"top\"\u003e\n \u003cp\u003e61.1\u0026plusmn;10.4\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.24231464737794%\" valign=\"top\"\u003e\n \u003cp\u003e62.8\u0026plusmn;17.4\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.370705244122966%\" valign=\"top\"\u003e\n \u003cp\u003e-0.444\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.2748643761302%\" valign=\"top\"\u003e\n \u003cp\u003e0.659\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.678119349005424%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eAfter 3 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.43399638336347%\" valign=\"top\"\u003e\n \u003cp\u003e55.5\u0026plusmn;11.1\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.24231464737794%\" valign=\"top\"\u003e\n \u003cp\u003e48.8\u0026plusmn;7.5\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.370705244122966%\" valign=\"top\"\u003e\n \u003cp\u003e2.725\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.2748643761302%\" valign=\"top\"\u003e\n \u003cp\u003e0.009\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"25.678119349005424%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eAfter 6 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.43399638336347%\" valign=\"top\"\u003e\n \u003cp\u003e48.1\u0026plusmn;8.8\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.24231464737794%\" valign=\"top\"\u003e\n \u003cp\u003e40.9\u0026plusmn;7.2\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.370705244122966%\" valign=\"top\"\u003e\n \u003cp\u003e-3.351\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.2748643761302%\" valign=\"top\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"68.35443037974683%\" colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003eTime effect\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.645569620253166%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eF\u003c/em\u003e=348.157,\u003cem\u003e\u0026nbsp;P\u003c/em\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"68.35443037974683%\" colspan=\"4\" valign=\"top\"\u003e\n \u003cp\u003eTime and group interaction effects\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.645569620253166%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eF\u003c/em\u003e =41.159, \u003cem\u003eP\u003c/em\u003e＜0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eData are presented as mean \u0026plusmn; SD, NRS = numerical rating scale. \u003csup\u003e*\u003c/sup\u003e\u003cem\u003eP\u003c/em\u003e＜0.05, \u003csup\u003e**\u003c/sup\u003e\u003cem\u003eP\u003c/em\u003e＜0.01, \u003csup\u003e***\u003c/sup\u003e\u003cem\u003eP\u003c/em\u003e＜0.001, compared to the baseline in each group.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 3 Oral morphine equivalent and Pregabalin consumption of the studied groups\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"20.43399638336347%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.678119349005424%\" valign=\"top\"\u003e\n \u003cp\u003eCRF (n=28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.24231464737794%\" valign=\"top\"\u003e\n \u003cp\u003eH-PRF(n=29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.370705244122966%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003et\u003c/em\u003e-value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.2748643761302%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"5\" valign=\"top\"\u003e\n \u003cp\u003eOral morphine equivalent (mg)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20.43399638336347%\" valign=\"top\"\u003e\n \u003cp\u003epre\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.678119349005424%\" valign=\"top\"\u003e\n \u003cp\u003e375.56\u0026plusmn;45.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.24231464737794%\" valign=\"top\"\u003e\n \u003cp\u003e386.08\u0026plusmn;50.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.370705244122966%\" valign=\"top\"\u003e\n \u003cp\u003e-0.822\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.2748643761302%\" valign=\"top\"\u003e\n \u003cp\u003e0.414\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20.43399638336347%\" valign=\"top\"\u003e\n \u003cp\u003eAfter 6 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.678119349005424%\" valign=\"top\"\u003e\n \u003cp\u003e486.81\u0026plusmn;55.42\u003csup\u003e***\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.24231464737794%\" valign=\"top\"\u003e\n \u003cp\u003e505.87\u0026plusmn;51.36\u003csup\u003e***\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.370705244122966%\" valign=\"top\"\u003e\n \u003cp\u003e-1.347\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.2748643761302%\" valign=\"top\"\u003e\n \u003cp\u003e0.183\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"5\" valign=\"top\"\u003e\n \u003cp\u003ePregabalin consumption (mg)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20.43399638336347%\" valign=\"top\"\u003e\n \u003cp\u003epre\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.678119349005424%\" valign=\"top\"\u003e\n \u003cp\u003e340.32\u0026plusmn;51.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.24231464737794%\" valign=\"top\"\u003e\n \u003cp\u003e351.85\u0026plusmn;62.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.370705244122966%\" valign=\"top\"\u003e\n \u003cp\u003e-0.081\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.2748643761302%\" valign=\"top\"\u003e\n \u003cp\u003e0.937\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"20.43399638336347%\" valign=\"top\"\u003e\n \u003cp\u003eAfter 6 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.678119349005424%\" valign=\"top\"\u003e\n \u003cp\u003e358.09\u0026plusmn;67.82\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.24231464737794%\" valign=\"top\"\u003e\n \u003cp\u003e368.87\u0026plusmn;71.21\u003csup\u003e#\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.370705244122966%\" valign=\"top\"\u003e\n \u003cp\u003e-0.585\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.2748643761302%\" valign=\"top\"\u003e\n \u003cp\u003e0.561\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eData are presented as mean \u0026plusmn; SD. \u003csup\u003e*\u003c/sup\u003e\u003cem\u003eP\u003c/em\u003e＜0.05, \u003csup\u003e**\u003c/sup\u003e\u003cem\u003eP\u003c/em\u003e＜0.01, \u003csup\u003e***\u003c/sup\u003e\u003cem\u003eP\u003c/em\u003e＜0.001, \u003csup\u003e#\u003c/sup\u003e\u003cem\u003eP\u003c/em\u003e＞0.05, compared to the baseline in each group.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 4 The frequency of adverse events observed within the groups under investigation.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.16216216216216%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.45945945945946%\" valign=\"top\"\u003e\n \u003cp\u003eCRF (n=28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.45945945945946%\" valign=\"top\"\u003e\n \u003cp\u003eH-PRF(n=29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.45945945945946%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026chi;\u003csup\u003e2\u003c/sup\u003e\u003c/em\u003e--value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.45945945945946%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.16216216216216%\" valign=\"top\"\u003e\n \u003cp\u003ebleeding\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.45945945945946%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.45945945945946%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.45945945945946%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.45945945945946%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.16216216216216%\" valign=\"top\"\u003e\n \u003cp\u003elocal infection,\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.45945945945946%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.45945945945946%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.45945945945946%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.45945945945946%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.16216216216216%\" valign=\"top\"\u003e\n \u003cp\u003erectal injury\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.45945945945946%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.45945945945946%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.45945945945946%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.45945945945946%\" valign=\"top\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"5\" valign=\"top\"\u003e\n \u003cp\u003eperineal numbness\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.16216216216216%\" valign=\"top\"\u003e\n \u003cp\u003eAfter 24 hours\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.45945945945946%\" valign=\"top\"\u003e\n \u003cp\u003e16 (57.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.45945945945946%\" valign=\"top\"\u003e\n \u003cp\u003e15 (51.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.45945945945946%\" valign=\"top\"\u003e\n \u003cp\u003e0.169\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.45945945945946%\" valign=\"top\"\u003e\n \u003cp\u003e0.792\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"22.16216216216216%\" valign=\"top\"\u003e\n \u003cp\u003eAfter 6 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.45945945945946%\" valign=\"top\"\u003e\n \u003cp\u003e6 (21.4)\u003csup\u003e\u0026nbsp;**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.45945945945946%\" valign=\"top\"\u003e\n \u003cp\u003e8 (27.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.45945945945946%\" valign=\"top\"\u003e\n \u003cp\u003e0.292\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.45945945945946%\" valign=\"top\"\u003e\n \u003cp\u003e0.760\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"ganglion impar, conventional radiofrequency, pulsed radiofrequency, perineal pain, cancer pain","lastPublishedDoi":"10.21203/rs.3.rs-4149738/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4149738/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective \u003c/strong\u003eAdvanced rectal cancer is a common cause of perineal pain and research on the use of radiofrequency therapy for the treatment of this pain is limited. In the present study, we aimed to compare the effectiveness and safety of conventional radiofrequency (CRF) and high-voltage long-term pulsed radiofrequency (H-PRF) of radiofrequency therapy in the management of perineal pain in advanced rectal cancer.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods \u003c/strong\u003eA total of 72 patients with advanced rectal cancer experiencing perineal pain were enrolled and randomly assigned to either the group CRF or H-PRF in a double-blind trial. The primary focus was on assessing perineal pain using NRS scores at various time points. Secondary outcomes included the duration of maintaining a sitting position, depression scores, sleep quality, consumption of Oral Morphine Equivalent and Pregabalin, and the incidence of perineal numbness.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults \u003c/strong\u003eA total of 57 patients (28 patients in the group CRF and 29 patients in the H- group H-PRF) were investigated. At all observation time points postoperatively, both groups of patients exhibited significant reductions in pain, enhancements in depression, improvements in sleep quality, and increased duration of sitting compared to their baseline measurements (\u003cem\u003eP\u003c/em\u003e＜0.05). During the 3 months and 6 months follow-up period, the group CRF exhibited significant reduction in pain, improvement in depression, sleep quality, and increased the time of keeping a sitting position compared with the group H-PRF. (\u003cem\u003eP\u003c/em\u003e＜0.05). The consumption of oral morphine equivalent and Pregabalin as well as the incidence of perineal numbness were not significantly different between groups (\u003cem\u003eP\u003c/em\u003e\u0026gt;0.05).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion \u003c/strong\u003eOur results demonstrate that application of CRF and H-PRF in ganglion impar to reduce perineal pain and improve the quality of life of patients with advanced rectal cancer is safe and effective. However, the long-term effect of CRF is better compared with that of H-PRF.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial registration\u003c/strong\u003e This study was registered was registered with the Chinese Clinical Trial Registry (ChiCTR2200061800, 07/02/2022).\u003c/p\u003e","manuscriptTitle":"Conventional versus high-voltage, long-term pulse Radiofrequency of ganglion impar in perineal pain with advanced rectal cancer: A Randomized, Double-Blind Controlled Trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-03-29 18:57:51","doi":"10.21203/rs.3.rs-4149738/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"599344a9-e77f-425d-bd02-e5666dbc9f13","owner":[],"postedDate":"March 29th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-06-13T04:53:19+00:00","versionOfRecord":[],"versionCreatedAt":"2024-03-29 18:57:51","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4149738","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4149738","identity":"rs-4149738","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}