Topical capsaicin 8% differentially blocks activation of nociceptors by mechanical, heat, and electrical stimuli in human skin.

Abstract

Capsaicin can cause long-lasting analgesia in patients but the time course of the underlying C-nociceptor functional loss remains unclear. We investigated functional loss and sensory recovery of "polymodal" and "silent" C-nociceptors after topical 8% capsaicin treatment for 12 weeks. The volar forearms of 20 healthy volunteers received two 8% capsaicin patches (1.5 cm2, Qutenza) spaced 2 cm apart and one placebo patch over 4 consecutive days. Sensitivity of C-nociceptors was evaluated weekly by using suprathreshold heat, mechanical impact, pinprick, and sinusoidal electrical stimulation. Assessment areas were denervated skin sites, the nondenervated secondary zone adjacent to one capsaicin patch, in-between the 2 capsaicin patches, the placebo patch, and untreated control skin. Laser Doppler imaging was used to evaluate skin blood flow changes associated with electrical C-nociceptor activation. Functional impairment after capsaicin treatment varied dramatically in completeness and time course of recovery to control levels: although heat pain and axon reflex flare were completely abolished, mechanical impact pain was only marginally decreased. Heat pain and pain induced by single (1 Hz) electrical pulses gradually recovered in few weeks, whereas the axon reflex flare and pain to tonic 1-minute (4 Hz) electrical stimulation were inhibited for months. Our results confirm the essential role of capsaicin-sensitive nociceptors for heat pain. In contrast, mechanical impact pain was only marginally and transiently reduced suggesting alternative transduction routes or capsaicin-insensitive nociceptors. Only pain to tonic C-fiber stimulation required months for recovery, thus resembling long-lasting analgesic effects in capsaicin-treated patients.