Neurofilament Light Chain in Fibromyalgia: Correlation With Central and Peripheral Nervous System Dysfunction

ABSTRACT Background Fibromyalgia (FM) is a chronic pain syndrome in which central sensitization has been suggested. Several patients also present with small fibre pathology. Neurofilament light chain (NfL) is a biomarker of axonal injury, but its role in FM remains unclear. We evaluated serum NfL in FM patients and tested possible correlations between NfL levels, clinical features, dysfunction at the central level assessed with a cognitive battery, and small fibre pathology assessed with skin biopsy. Methods We conducted an observational case–control study including 70 FM patients and 55 healthy controls. Serum NfL was measured using the LUMIPULSE G600II platform. Clinical assessment included pain (WPI), disability (FIQ), sleep (MOS Sleep Scale), and neuropsychological testing (MoCA and an executive function battery). Forty patients underwent skin biopsy with intraepidermal nerve fibre density (IENFD) quantification. Group comparisons were performed with non‐parametric tests and correlations using Spearman coefficients. Results FM patients showed higher NfL levels compared to controls, independent of age. In both groups, NfL correlated positively with age ( ρ  = 0.25, p  = 0.005). Among FM patients, NfL values did not differ between those with normal skin biopsy and those with proximal or combined proximal–distal denervation, and NfL did not correlate with IENFD. NfL was unrelated to disease duration, pain scores, sleep duration, or cognitive performance. The only clinical correlation observed was an association with disability (FIQ; ρ  = 0.29, p  = 0.02). Conclusions Serum NfL is elevated in FM but not linked to small fibre pathology or cognitive impairment. Instead, it may reflect neuronal changes related to disease burden. Significance These findings support the concept of FM as a neurogenic disorder and suggest serum NfL as a potential biomarker of neuronal stress in chronic pain, although it is not specific for peripheral nerve damage or cognitive dysfunction.