Serum neurofilament light chain in fibromyalgia: comparative evidence of neuronal injury across chronic pain conditions.

INTRODUCTION: Evidence increasingly shows small nerve fibre pathology in subsets of people with fibromyalgia through skin biopsy, corneal confocal microscopy, and microneurography. However, blood-based biomarkers of ongoing neuronal damage, particularly neurofilament light chain (NfL), an axonal structural protein, are not well established. OBJECTIVES: The aim of this study was to evaluate serum NfL concentrations in fibromyalgia compared with other chronic pain conditions and assess their relationship with neuropathic-like pain. METHODS: We measured serum NfL using Simoa SR-X NF Light v2 digital-immunoassay in 60 participants with fibromyalgia, 61 with endometriosis (another traditionally considered non-neuropathic pain condition), 24 with small fibre neuropathy (a recognised neuropathic pain condition), and 30 healthy controls. Serum NfL concentrations were compared between the groups controlling for age and body mass index. Neuropathic-like pain was assessed using the painDETECT questionnaire for fibromyalgia and endometriosis and NeuPSIG grading criteria for small fibre neuropathy. RESULTS: Compared with healthy controls (mean concentration = 6.77 pg/mL, Z-score = -1.15), serum NfL concentrations were significantly elevated in fibromyalgia (mean concentration = 8.52 pg/mL P = 0.048; Z-score = -0.30, and P = 0.006) and small fibre neuropathy (mean concentration = 8.98 pg/mL, P = 0.004; Z-score = 0.23, P = 0.0001), with endometriosis representing an intermediate phenotype (mean concentration = 5.57 pg/mL, P = 0.44; Z-score = -0.41, P = 0.024). Using PainDETECT, 44% of fibromyalgia and 26% of endometriosis participants met likely neuropathic pain criteria; using NeupSIG grading, 96% of small fibre neuropathy participants met probable/definite criteria. CONCLUSION: Our study provides serological evidence of nerve pathology in fibromyalgia at comparable levels with small fibre neuropathy, although this did not correlate with neuropathic-like pain presence or severity. These findings highlight the need for subgroup-specific treatment strategies.