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The following is a summary of “Slow depolarizing electrical stimuli reveal differential time courses of nociceptor recovery after prolonged topical capsaicin in human skin,” published in the September 2024 issue of Pain by Gutti et al.

Researchers conducted a retrospective study investigating the de-functionalization and temporal functional recovery of C-nociceptor-evoked pain from 4 days of topical 8% capsaicin application. 

They applied capsaicin and placebo patches to the human forearm skin of 14 participants. They recorded cold, warmth, and heat pain thresholds, pain numerical rating scale (NRS) to electrical and thermal (48°C, 5 s) stimuli, and axon reflex flare weekly for 49 days. Mechanical and heat-sensitive (‘polymodal’) nociceptors were activated by single electrical half-period sinusoidal pulses (0.5 s, 1 Hz), and 4 Hz sinusoidal stimuli activated mechanical and heat-insensitive (‘silent’) nociceptors.

The results showed capsaicin abolished heat pain. Sensation to electrical sinusoidal stimulation decreased but was not completely abolished during treatment. Pain to electrical 1 Hz ‘polymodal’ nociceptor stimulation took longer to recover (35 days) than pain ratings to 4 Hz 2.5 s sinusoidal stimulation activating ‘polymodal’ and ‘silent’ nociceptors (21 days). Heat pain was not affected by the placebo from day 21 to 49. Axon reflex flare was abolished during capsaicin and only recovered to approximately 50% even after 49 days.

They concluded that capsaicin abolishes heat transduction at terminal nociceptive endings but does not affect small-diameter axon sensitivity to electrical stimulation, suggesting differential time courses of functional regeneration for C-nociceptor subtypes after capsaicin.

Source: onlinelibrary.wiley.com/doi/full/10.1002/ejp.4726