Capsaicin Induces Degeneration of Cutaneous Autonomic Nerve Fibers

Objective: To determine the effects of topical application of capsaicin on cutaneous autonomic nerves.

Methods: Thirty-two healthy subjects underwent occlusive application of 0.1% capsaicin cream (or placebo) for 48 hours. Subjects were followed for 6 months with serial assessments of sudomotor, vasomotor, pilomotor, and sensory function with simultaneous assessment of innervation through skin biopsies.

Results: There were reductions in sudomotor, vasomotor, pilomotor, and sensory function in capsaicin-treated subjects (p < 0.01 vs. placebo). Sensory function declined more rapidly than autonomic function, reaching a nadir by Day 6, whereas autonomic function reached a nadir by Day 16. There were reductions in sudomotor, vasomotor, pilomotor, and sensory nerve fiber densities in capsaicin-treated subjects (p < 0.01 vs. placebo). Intraepidermal nerve fiber density declined maximally by 6 days, whereas autonomic nerve fiber densities reached maximal degeneration by Day 16. Conversely, autonomic nerves generally regenerated more rapidly than sensory nerves, requiring 40-50 days to return to baseline levels, whereas sensory fibers required 140-150 days to return to baseline.

Interpretation: Topical capsaicin leads to degeneration of sudomotor, vasomotor, and pilomotor nerves accompanied by impairment of sudomotor, vasomotor, and pilomotor function. These results suggest the susceptibility and/or pathophysiologic mechanisms of nerve damage may differ between autonomic and sensory nerve fibers treated with capsaicin and enhances the capsaicin model for the study of disease-modifying agents. The data suggest caution should be taken when topical capsaicin is applied to skin surfaces at risk for ulceration, particularly in neuropathic conditions characterized by sensory and autonomic impairment.