Discriminative role of inflammatory indices in clinical response to ganglion impar blockade: A retrospective cohort study.

This study demonstrates that GIB is an effective treatment for nonmalignant coccydynia. Our findings indicate that higher pre-procedural inflammatory indices (PLR and SII) and certain coccygeal morphologies (types III and V) are associated with clinical response. While these associations are correlative rather than causal, they highlight the potential role of readily available hematologic markers in predicting treatment outcomes. Anatomical variations and inflammatory indices should therefore be considered as supportive parameters within individualized treatment planning, rather than as standalone decision criteria. Further prospective studies with larger cohorts and extended follow-up are warranted to validate and refine these observations.

Coccydynia is a chronic pain syndrome characterized by pain and tenderness in the sacrococcygeal region, particularly aggravated by sitting. [ 1 ] While external traumas (falling backward, sitting on a hard surface for a long time) or internal traumas (childbirth) are the most common precipitating factors, obesity and female gender are significant epidemiologic risk modifiers. [ 2 , 3 ] The complex pathophysiology of coccydynia stems from the anatomical structure of the coccyx and the biomechanical involvement of regional nerves. It arises from a complex interaction of inflammatory, neuropathic, and central sensitization mechanisms. [ 4 , 5 ] Central sensitization is the increased sensitivity of the central nervous system (CNS) to nociceptive stimuli. Prolonged inflammatory signals induce plasticity in the pain pathways of the CNS. [ 6 ] Specific to coccydynia, biomechanical trauma leads to chronic irritation of the coccygeal nerve roots, increasing central sensitivity in the long term and potentially triggering sympathetic hyperactivity. [ 7 ] These mechanisms support sympathetic blocks, such as the ganglion impar blockade (GIB), as an effective treatment option. [ 8 ] Conservative treatments like ergonomic modifications (doughnut or ring-shaped cushions) and nonsteroidal anti-inflammatory drugs are initial therapies and are successful in 90% of coccydynia patients. [ 9 , 10 ] Refractory cases often require interventional or surgical treatment. The ganglion impar, an autonomic structure anterior to the sacrococcygeal joint, serves as a conduit for afferent nerve fibers from the perineal region. [ 11 ] In recent years, GIB performed under fluoroscopy guidance has emerged as an effective method for reducing both somatic and neuropathic pain. [ 11 , 12 ] This procedure aims to alleviate pain through temporary or permanent inhibition of nociceptive transmission. Despite generally favorable outcomes, a clinically relevant subset of patients fails to achieve adequate analgesia after GIB. Treatment failure may be attributed to various factors such as patient selection, anatomical variations, comorbidities, and application techniques. [ 13 , 14 ] Additionally, central sensitization and inflammation are hypothesized to play a role in treatment failure in these cases. Persistent inflammation can contribute to ongoing pain by sustaining nociceptive signaling and enhancing the excitability of pain pathways. Inflammatory mediators sensitize both peripheral nociceptors and central neurons within the CNS, thereby facilitating central sensitization and potentially causing perpetuating pain even after peripheral interventions. [ 15 ] Biomarkers like C-reactive protein and erythrocyte sedimentation rate are commonly used to assess inflammation. Recently, novel inflammatory indices, such as the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), lymphocyte-to-monocyte ratio (LMR), and systemic inflammation response index (SIRI) have been developed based on hematological parameters to capture different aspects of inflammation. Given their accessibility, cost-effectiveness, and enhanced sensitivity, NLR, PLR, LMR, SII, and SIRI have been increasingly investigated as potential biomarkers for the assessment and monitoring of systemic inflammatory activity. NLR and SIRI have been identified as independent risk factors in cancer, acute cerebrovascular events, and rheumatic diseases. [ 16 - 18 ] However, despite the growing interest in inflammatory biomarkers, their application in pain-related conditions, particularly in relation to interventional pain management, remains limited. Notably, a study showed that the combined detection of mean platelet volume and NLR had significant clinical predictive value for the postoperative effectiveness of splanchnic neurolysis in pancreatic cancer patients. [ 19 ] Nonetheless, the potential of similar hematologic indices to predict an inadequate response to GIB in coccydynia has not been systematically investigated. Given this background, we sought to evaluate whether the hematologic indices NLR, PLR, LMR, SII, and SIRI, together with coccygeal morphology per the Postacchini–Massobrio classification, can distinguish responders from nonresponders among patients undergoing fluoroscopy-guided GIB for chronic coccydynia.

Conceptualization: Gulcin Babaoglu. Data curation: Gulcin Babaoglu, Ulku Sabuncu, Sukriye Dadali, Ali Costu. Formal analysis: Gulcin Babaoglu, Ulku Sabuncu. Investigation: Gulcin Babaoglu, Ulku Sabuncu, Sukriye Dadali, Ali Costu, Erkan Yavuz Akcaboy. Methodology: Gulcin Babaoglu, Sukriye Dadali, Ali Costu, Erkan Yavuz Akcaboy. Supervision: Ulku Sabuncu, Erkan Yavuz Akcaboy. Visualization: Gulcin Babaoglu. Writing – original draft: Gulcin Babaoglu, Sukriye Dadali, Ali Costu. Writing – review & editing: Gulcin Babaoglu, Ulku Sabuncu, Sukriye Dadali, Ali Costu, Erkan Yavuz Akcaboy.

This study was designed and reported in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines and was approved by the Scientific and Ethical Review Board of Ankara Bilkent City Hospital (Approval number: TABED2-25-948; Date: February 19, 2025). The requirement for informed consent was waived by the committee due to the retrospective nature of the study. Patients who underwent GIB at the Ankara Bilkent City Hospital Pain Medicine clinic between January 2022 and January 2025 were retrospectively evaluated. Patients aged 18 years and older who underwent GIB due to coccydynia lasting longer than 3 months were included. Patients with incomplete medical records, those lost to follow-up, those who underwent GIB for cancer-related pain, those with rheumatic diseases, cases with technical failure, and patients who had previously undergone coccyx surgery were excluded from the study. All procedures were performed in the operating room under sterile conditions and with monitoring during the procedure. With the patient in the prone position, the intergluteal region was sterilized, and skin anesthesia was provided by administering 2 mL of local anesthetic (2% prilocaine). The sacrococcygeal joint was visualized using C-arm fluoroscopy. A 22-gauge spinal needle was inserted midline into the sacrococcygeal junction. In the lateral fluoroscopic view, when the needle tip reached the ventral aspect of the coccyx, its position was confirmed by injecting 1 mL of nonionic contrast and observing the spread, achieving an “inverted comma” appearance. Then, 3 mL of 0.5% bupivacaine and 2 mL (8 mg) of dexamethasone were injected into the area (Fig. 1 ). Fluoroscopic view of ganglion impar blockade. We retrospectively reviewed 330 procedures. When a patient had undergone more than 1 procedure, only the first intervention was retained for analysis, leading to the exclusion of 61 subsequent procedures from the same patients. Additional exclusions were concomitant neurolysis (n = 53), cancer-related pain (n = 31), underlying rheumatologic disease (n = 7), prior coccygeal surgery (n = 4), incomplete medical records (n = 12), and absence of follow-up data (n = 43). The remaining 119 unique patients constituted the final study cohort (Fig. 2 ). Flowchart of patients enrollment and exclusion process. Age, gender, body mass index (BMI), duration of pain, and history of trauma were obtained by retrospectively reviewing medical records. Pain intensity was quantified with a 10-cm visual analogue scale (VAS; 0 = no pain, 10 = worst imaginable pain) recorded immediately before the ganglion impar block and at the 1-month follow-up. The 7-point global perceived effect (GPE) score, which provides an integrated assessment of pain and functionality, was recorded at the 1-month post-procedure follow-up. Digital coccygeal radiographs were retrieved from electronic records and categorized according to the modified Postacchini–Massobrio classification. [ 20 , 21 ] Coccyx curvature was classified as follows: type I: normal curvature, type II: coccyx more prominently curved and anteriorly oriented, type III: very sharp anterior angulation, type IV: anterior subluxation at the sacrococcygeal or intercoccygeal joint, type V: coccygeal retroversion, type VI: scoliotic deformation. Routine laboratory data obtained 1 to 7 days before the ganglion impar block were retrieved. From these data we calculated the NLR, PLR, LMR, SII, and SIRI. SII was calculated as the absolute platelet count (APC) multiplied by the absolute neutrophil count (ANC) and divided by the absolute lymphocyte count (ALC; SII = APC × ANC/ALC), while SIRI was calculated as the absolute monocyte count (AMC) multiplied by the ANC and divided by the ALC (SIRI = AMC × ANC/ALC). Additionally, NLR was calculated by dividing the ANC by the ALC, PLR by dividing the APC by the ALC, and LMR by dividing the ALC by the AMC. At the 1-month follow-up, patients were classified as responders if they reported either a ≥50% reduction in their baseline VAS score or a GPE score of 6 or 7. Patients not meeting these criteria (i.e., VAS reduction < 50% and a GPE score of ≤5) were classified as nonresponders. Hematologic indices were subsequently analyzed to evaluate their discriminative performance in distinguishing responders from nonresponders after GIB. All statistical procedures were conducted using IBM SPSS Statistics for Windows, version 25.0 (IBM Corp., Armonk). Continuous data were assessed for normality using the Shapiro–Wilk test and visual inspection of histograms and quantile–quantile plots. Normally distributed variables are presented as mean ± standard deviation, whereas non-normal variables are reported as median with interquartile range (IQR); categorical data are summarized as frequencies and percentages. Responders and nonresponders were compared with Student t test for parametric data, the Mann–Whitney U -test for nonparametric data, and Pearson’s χ 2 test or Fisher’s exact test for categorical variables, as appropriate. Discriminative performance of each hematologic index was evaluated by receiver-operating-characteristic analysis, with the area under the curve (AUC) and 95% confidence intervals (CI) calculated and optimal cutoffs derived from the Youden statistic. All analyses were 2-tailed, and statistical significance was set at P  < .05.

A total of 119 patients were included in the study, with a predominant female population (79.8%). The mean age of the patients was 44.8 ± 12.7 years, and the mean BMI was 26.6 ± 4.0 kg/m 2 . The median duration of pain was 24 months (IQR 8–60 months). A history of trauma was reported in 45.4% of the patients. The mean baseline VAS score was 7.83 ± 0.90. According to the Postacchini–Massobrio classification, 31.9% of the patients were classified as type I, 27.7% as type II, and 22.7% as type III, while more advanced stages (types IV–VI) were less frequent (10.1%, 6.7%, and 0.8%, respectively). A positive treatment response was observed in 74 patients (62.2%). The response rate was significantly higher in females compared to males (67.4% vs 41.7%, P  = .02), suggesting a potential sex-based difference in treatment outcomes. When comparing responders and nonresponders, no significant differences were observed in age (44.4 ± 13.7 vs 45.5 ± 11.1 years, P  = .64), BMI (26.5 ± 4.0 vs 26.8 ± 4.0, P  = .66), baseline VAS score (7.9 ± 0.9 vs 7.8 ± 0.8, P  = .76), history of trauma (44.6% vs 46.7%, P  = .83), or pain duration (24 [IQR 9–48] vs 24 [IQR 6–96] months, P  = .61). Among inflammatory markers, responders exhibited significantly higher PLR (123.5 [105.5–158.2] vs 110.0 [86.0–137.0], P  = .006) and SII (566.5 [386.3–697.5] vs 447.8 [349.6–551.4], P  = .023) compared to nonresponders. However, NLR, SIRI, and LMR did not differ significantly between groups ( P  > .05; Table 1 ). Comparison of clinical and inflammatory markers between responder and nonresponder groups. BMI = body mass index, CRP = C-reactive protein, IQR = interquartile range, LMR = lymphocyte-to-monocyte ratio, NLR = neutrophil-to-lymphocyte ratio, PLR = platelet-to-lymphocyte ratio, SD = standard deviation, SII = systemic immune-inflammation index, SIRI = systemic inflammation response index, VAS = visual analog scale. Regarding the Postacchini–Massobrio classification, response rates varied among different grades but did not reach statistical significance overall ( P  = .25). Types I and II were more common among responders (31% each), while nonresponders had a higher proportion of type III patients (31%). Non-responsiveness was highest in type III (51.9%) and type V (50.0%). Type IV had the lowest nonresponsive rate with a percentage of 16.7%. Type VI had only 1 patient, who was responsive. The non-responsiveness rates in type I and type II were 39.5% and 30.3%. Given the high rates of nonresponse in types III and V, we performed a combined analysis. Patients with type III or V morphology had a significantly lower response rate compared to those with other morphologies (48.6% vs 67.9%, respectively; P  = .048). The AUC values for the tested inflammatory indices varied in their ability to distinguish between responders and nonresponders (Table 2 ). Among them, PLR demonstrated the highest discriminative ability (AUC = 0.650, 95% CI: 0.54–0.75, P  = .006). The optimal cutoff value, derived from the Youden statistic, was 93.58, which yielded a sensitivity of 95% and a specificity of 33%. Similarly, SII showed moderate predictive value (AUC = 0.621, 95% CI: 0.53–0.73, P  = .028), with a cutoff of 565.00 providing a sensitivity of 51% and a specificity of 78%. In contrast, NLR (AUC = 0.574, 95% CI: 0.47–0.68, P  = .177, cutoff = 2.10), SIRI (AUC = 0.522, 95% CI: 0.41–0.63, P  = .685, cutoff = 0.61), and LMR (AUC = 0.473, 95% CI: 0.36–0.58, P  = .620, cutoff = 7.00) did not demonstrate significant discriminative power (Fig. 3 ). Diagnostic performance metrics of hematologic indices for discriminating responders and nonresponders. AUC = area under the receiver operating characteristic curve, CI = confidence interval, LMR = lymphocyte-to-monocyte ratio, NLR = neutrophil-to-lymphocyte ratio, NPV = negative predictive value, PLR = platelet-to-lymphocyte ratio, PPV = positive predictive value, SII = systemic immune-inflammation index, SIRI = systemic inflammation response index. Receiver operating characteristic (ROC) curves of inflammatory biomarkers. AUC = area under the receiver operating characteristic curve, FPR = false positive rate, LMR = lymphocyte-to-monocyte ratio, NLR = neutrophil-to-lymphocyte ratio, PLR = platelet-to-lymphocyte ratio, ROC = receiver operating characteristic, SII = systemic immune-inflammation index, SIRI = systemic inflammation response index, TPR = true positive rate.

In this study, we found that GIB is an effective intervention for chronic coccydynia, with a response rate of 62.2%. Our primary findings indicate that higher pre-procedural PLR and SII values were associated with a positive treatment response, while coccygeal morphologies type III and V were associated with poorer outcomes. The ganglion impar is responsible for the integration of somatic and visceral nociceptive inputs from the pelvis, perineum, and anococcygeal region, occupies a central role in pain modulation. [ 22 ] Therefore, blockade applications targeting the ganglion impar are recommended as an effective treatment approach, especially for chronic pelvic pain, coccydynia, and some cancer pains. [ 11 - 14 ] In our study, ≥50% reduction in pain scores was achieved in 62.2% of patients, which is consistent with the findings reported by Sir and Eksert at 3 weeks and 3 months. [ 23 ] Similarly, another study reported a success rate of 69.6% at 3 months. [ 14 ] However, the lower success rate observed in our study compared to the 82% reported by Gündüz et al at a 6-month follow-up is noteworthy. [ 24 ] This discrepancy could be attributed to several factors, including differences in patient populations, follow-up duration, or definitions of success. Our shorter follow-up period (1 month vs 6 months) may also play a role. Regarding gender distribution, the literature has reported a higher prevalence of coccydynia in women. [ 2 , 8 ] This has been attributed to the anatomically wider female pelvis and the coccyx being more vulnerable to trauma. Pressure exerted on the pelvic floor during childbirth can cause damage to connective tissues, increasing the risk of developing coccydynia in the post-partum period. [ 8 ] In this context, the proportion of female patients being 79.8% in our study is consistent with the literature and supports the notion that gender may be a predisposing factor. Coccygeal morphology has long been recognized as a potential factor in the etiology of coccydynia. The radiological classification system described by Postacchini and Massobrio provided a foundational framework for understanding the clinical implications of morphological variations, [ 20 ] and was further expanded by Nathan et al. [ 21 ] Curved or sharply angulated structures, such as type II, III, and IV, are more susceptible to recurrent microtraumas and, consequently, more frequently associated with coccydynia. Kaya et al reported that morphologies other than type I were associated with a better response to blockade treatment. [ 25 ] However, in our study, patients with type III and type V morphologies demonstrated a significantly poorer treatment response compared to other types. This discrepancy highlights the limited predictive capacity of the Postacchini–Massobrio classification in forecasting treatment success. Similarly, Çelenlioğlu and Sir also stated that there was no significant difference in treatment success according to morphological types, but the presence of permanent subluxation could negatively affect treatment efficacy. [ 14 ] In another study utilizing dynamic radiographic assessment of coccygeal morphology, no significant difference in treatment response was observed between patients with mobile and immobile coccyges. [ 26 ] Therefore, it can be inferred that while the Postacchini–Massobrio classification alone has limited predictive value for GIB success, specific anatomical abnormalities (such as permanent subluxation) may impact treatment success. The critical role of inflammation in the pathophysiology of chronic pain syndromes is increasingly recognized. [ 27 , 28 ] Initially a physiological response to tissue injury, the inflammatory process is characterized by the activation of immune cells such as platelets, monocytes, and macrophages, leading to the release of proinflammatory mediators. However, the persistence of this response contributes to the development of chronic inflammation, a fundamental pathological feature implicated in various chronic pain conditions including endometriosis, osteoarthritis, fibromyalgia, and chronic postsurgical pain. [ 29 - 32 ] In response to immune activation, hematological alterations such as increased neutrophil, monocyte, and platelet counts, and decreased lymphocyte counts (lymphopenia) can occur. [ 33 ] These dynamic changes have laid the foundation for the development of composite inflammatory indices, which provide practical biomarkers reflecting both the acute and chronic phases of the inflammatory process. In line with this, these indices such as the NLR, PLR, SII, and SIRI were found associated with chronic pain syndromes. [ 29 - 32 ] For instance, Shu et al reported that a ≥ 5-fold change in the postoperative-to-preoperative NLR was associated with the development of moderate to severe chronic postsurgical pain. [ 29 ] In studies involving fibromyalgia patients, elevated NLR and PLR values and decreased LMR values have been observed compared to healthy controls, suggesting that systemic inflammation, through immune dysfunction, may contribute to the pathogenesis of fibromyalgia. [ 30 ] Similarly, in osteoarthritis, increased levels of NLR, PLR, MLR (monocyte-to-lymphocyte ratio), and SIRI have been reported, with SIRI and NLR demonstrating strong discriminative capacity regarding disease activity. Notably, the combination of SIRI and C-reactive protein has been shown to provide superior predictive performance for disease activity. [ 31 ] In addition, a retrospective study investigating pancreatic cancer pain found that MPV and NLR independently and in combination predicted the efficacy of splanchnic neurolysis. Furthermore, preoperative lymphocyte count and PLR were significantly correlated with the severity of patient-reported pain. [ 19 ] In our study, pre-procedural PLR and SII values were significantly higher in patients who responded to treatment, and these 2 indices demonstrated the strongest discriminative performance. PLR exhibited the highest discriminative ability, with an AUC of 0.650, whereas SII demonstrated moderate ability with an AUC of 0.621. Conversely, other parameters, including NLR, SIRI, and LMR, did not show significant discriminative ability regarding treatment response ( P  > .05). These findings suggest that certain hemogram-derived inflammatory indices, particularly PLR and SII, may serve as useful adjuncts associated with the response to GIB in chronic coccydynia. However, reliance solely on these indices in clinical decision-making may be insufficient, and they should be interpreted within the broader clinical context. Despite its strengths, this study has limitations. First, its retrospective nature and single-center setting may introduce selection bias and limit the generalizability of the findings. Second, the sample size, although reasonable, may not have been sufficiently large to detect more subtle associations between inflammatory indices and treatment outcomes. Third, the follow-up period was relatively short, preventing the evaluation of long-term treatment efficacy and potential relapse rates. Fourth, although there was no change in concurrent analgesic medications, potential confounding factors such as psychological status and functional disability, were not systematically controlled or assessed. Finally, although hemogram-based indices offer practical advantages, they can be influenced by various nonspecific factors. Although the design does not permit direct mechanistic confirmation, the consistent associations between higher pre-procedural PLR and SII values and favorable clinical response provide meaningful indirect evidence linking systemic inflammatory activity to treatment outcomes. These results should be regarded as clinically relevant correlations rather than definitive proof of causality. Unmeasured variables such as pain chronicity, psychosocial factors, and functional impairment may also contribute to the observed outcomes. Nonetheless, the ease and low cost of hematologic indices offer a practical basis for hypothesis generation and individualized patient assessment, supporting their further evaluation in further studies.