745: Reduced Cerebrospinal Fluid Draxin and FcRL2 in Chronic Postoperative Inguinal Pain

Topic: Clinical Science
Subtopic: Pain category (ICD-11), Neuropathic pain , Neuroimmunology, Omics (Proteomics/Metabolomics/Transcriptomics/Genomics)

Background and Aims: Despite inguinal hernia repair being one of the most commonly performed surgical procedures worldwide, and high-impact chronic postherniorrhaphy inguinal pain (CPIP) affecting 1-3% of those operated upon [1], no previous study has examined neuroimmune mediators in the cerebrospinal fluid (CSF) of this patient population. Moreover, during the past two decades, neuroimmune signaling within the central nervous system (CNS) has emerged as a putative key mechanism underlying the development and maintenance of chronic neuropathic pain [2]. Data from preclinical models of neuropathic pain demonstrate elevated concentrations of proinflammatory cytokines, chemokines and neurotrophic factors at multiple levels of the neuraxis [3,4].

Methods: CPIP subjects (n=13) and healthy, pain-free, age- and sex-matched controls (n=13) completed questionnaires, 7-day actigraphy, quantitative sensory testing, and a cognitive battery. CSF was collected via lumbar puncture; protein levels were assessed using proximity extension assays (Olink Target96 panels, Inflammation and Neurology) and sparse partial least squares discriminant analysis (sPLS-DA) was used to identify proteins distinguishing groups.

Results: Median pain duration was 3.7 years. CPIP subjects frequently exhibited mechanical hypoesthesia, mechanical and pressure pain hyperalgesia, and dynamic mechanical allodynia in the operated groin. Subjective and objective sleep measures indicated pronounced sleep disturbance among CPIP subjects. With only one exception (word recognition test), CPIP subjects performed significantly worse than controls on all cognitive measures. The sPLS-DA model successfully separated groups with modest accuracy. Draxin and FcRL2 emerged as the top contributors to group discrimination (variable importance in projection >1.3; stability >0.5). Both proteins were reduced in the CSF of CPIP subjects relative to controls. A global shift in CSF proteins was observed, with 72% of proteins showing nominally lower levels in CPIP subjects. No significant group differences were found in CSF-plasma albumin quotient and there were no consistent univariate protein-symptom associations.

Conclusions: In this observational study, we provide the first evidence of reduced CSF levels of Draxin and FcRL2 in CPIP subjects, alongside a global shift toward lower neuroimmune protein expression. Furthermore, consistent with meta-analytic data [5], CPIP subjects frequently exhibited mechanical hypoesthesia, hyperalgesia, dynamic mechanical allodynia, and significantly decreased pressure pain detection thresholds in the operated groin. Both subjective and objective sleep measures indicated severe sleep disturbance among CPIP subjects. These findings were observed in the context of a well-characterized clinical phenotype marked by cutaneous deafferentation, pressure pain hyperalgesia, sleep disturbance, and subtle cognitive deficits. While preliminary and requiring replication in larger cohorts, our results suggest that CNS neuroimmune dysregulation may play a role in the pathophysiology of chronic postsurgical pain.

References: 1. Bjurstrom MF, Nicol AL, Amid PK, Chen DC. Pain control following inguinal herniorrhaphy: current perspectives. J Pain Res 2014;7(277-290.
2. Milligan ED, Watkins LR. Pathological and protective roles of glia in chronic pain. Nat Rev Neurosci 2009;10(1):23-36.
3. Grace PM, Hutchinson MR, Maier SF, Watkins LR. Pathological pain and the neuroimmune interface. Nat Rev Immunol 2014;14(4):217-231.
4. Sommer C, Leinders M, Uceyler N. Inflammation in the pathophysiology of neuropathic pain. Pain 2018;159(3):595-602.
5. Dubayev A, Jensen EK, Andersen KG, Bjurstrom MF, Werner MU. Quantitative somatosensory assessments in patients with persistent pain following groin hernia repair: A systematic review with a meta-analytical approach. PLoS One 2024;19(1):e0292800.

Presenting Author: Alexander Rosenström
Submitting Author: Alexander Rosenström

Senior Author: Martin Flores Bjurström

IASP 2026 Global Year theme of Neuropathic Pain: Yes

• Lisa Boström: MD - Lund University
• Mads U. Werner: MD, PhD - Copenhagen University Hospital
• Eva Kosek: MD, PhD - Karolinska Institutet, Uppsala University
• Martin Flores Bjurström: MD, PhD - Uppsala University