Peripheral and central nervous system correlates in fibromyalgia

Background: Fibromyalgia (FM) is a syndrome characterized by altered pain processing at central and peripheral level, whose pathophysiologic mechanisms remain obscure. We aimed at exploring the structural changes of peripheral nociceptor measured by skin biopsy, the functional changes of central nociceptive pathway assessed by laser-evoked potentials (LEP), and their correlation with clinical features and comorbidities. Methods: In all, 81 patients diagnosed with FM underwent skin biopsies with quantification of intraepidermal nerve fibre density (IENFD) at the thigh and distal leg, and LEP recording by stimulating hand, thigh and foot. Nerve conduction study (NCS), clinical features, comorbidity with migraine and mood disorders, and previous, non-active immune-mediated disorders were recorded. Results: Intraepidermal nerve fibre density was reduced in 85% of patients at the thigh and in 12.3% of patients at the distal leg, whereas it was normal in 14.8% of patients. N2P2 habituation index from laser stimulation at the thigh was altered in 97.5% of patients and correlated with reduced IENFD at the thigh. LEP latencies and amplitudes did not differ among groups. No association was found between IENFD, LEP, clinical features and comorbidities. Conclusions: Fibromyalgia patients most commonly showed a mild loss of peripheral nociceptors at the thigh rather than distal small fibre neuropathy. This finding was associated with an altered habituation index and strengthened the hypothesis that central sensitization plays a key role in the pathogenesis of the disease. Significance: Central impairment of pain processing likely underlies FM, which in most patients is associated with mild proximal small fibre pathology.