Small fiber pathology-a culprit for many painful disorders?

Small fiber neuropathies (SFNs) are a subgroup of sensory neuropathies that almost exclusively affect thinly myelinated A-delta or unmyelinated C-nerve fibers. Patients with SFN typically report acral burning pain, paresthesias, and dysesthesias, and sometimes itch manifesting particularly at toes and feet. Although neurological examination and standard neurophysiological assessment are normal to only marginally abnormal, special small nerve fiber tests may show functional, electrical, and morphological small fiber pathology. Interestingly, the application of small nerve fiber assessment tools has revealed similar findings also in other painful and nonpainful disorders, such as the complex regional pain syndrome, postherpetic neuralgia, or fibromyalgia syndrome. The diversity in clinical presentation, however, already implies that different pathophysiological mechanisms underlie small nerve fiber degeneration and regeneration in these disorders. This review aims at presenting current knowledge on small nerve fiber research and at intensifying the awareness for SFN vs small fiber pathology as a chance to learn about small nerve fiber pathophysiology.