Slow depolarizing electrical stimuli reveal differential time courses of nociceptor recovery after prolonged topical capsaicin in human skin
Background We examined de-functionalization and temporal functional recovery of C-nociceptor evoked pain after topical 8% capsaicin applied for 4 consecutive days. Methods Capsaicin and placebo patches were applied to human forearm skin (n = 14). Cold, warmth and heat pain thresholds, pain NRS to el...
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| Main Authors: | , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
February 2025
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| In: |
European journal of pain
Year: 2025, Volume: 29, Issue: 2, Pages: 1-15 |
| ISSN: | 1532-2149 |
| DOI: | 10.1002/ejp.4726 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.1002/ejp.4726 Verlag, kostenfrei, Volltext: http://onlinelibrary.wiley.com/doi/abs/10.1002/ejp.4726 
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| Author Notes: | Divya Tumbala Gutti, Richard Carr, Martin Schmelz, Roman Rukwied |
| Summary: | Background We examined de-functionalization and temporal functional recovery of C-nociceptor evoked pain after topical 8% capsaicin applied for 4 consecutive days. Methods Capsaicin and placebo patches were applied to human forearm skin (n = 14). Cold, warmth and heat pain thresholds, pain NRS to electrical and thermal (48°C, 5 s) stimuli and axon reflex flare were recorded weekly for 49 days. Mechanical and heat sensitive (‘polymodal’) nociceptors were activated by single electrical half-period sinusoidal pulses (0.5 s, 1 Hz). Mechanical and heat insensitive (‘silent’) nociceptors were activated by 4 Hz sinusoidal stimuli. Results Capsaicin abolished heat pain. Sensation to electrical sinusoidal stimulation was reduced but never abolished during the treatment. Pain to electrical 1 Hz ‘polymodal’ nociceptor stimulation took longer to recover than pain ratings to 4 Hz 2.5 s sinusoidal stimulation activating ‘polymodal’ and ‘silent’ nociceptors (35 vs. 21 days). Heat pain was indifferent to placebo from day 21-49. Axon reflex flare was abolished during capsaicin and only recovered to 50% even after 49 days. Conclusions Capsaicin abolishes heat transduction at terminal nociceptive endings, whereas small-diameter axons sensitive to sinusoidal electrical stimulation can still be activated. 1 Hz depolarizing stimuli evoke burst discharges, as demonstrated before, and recover slower after capsaicin than single pulses induced by 4 Hz. The difference in recovery suggests differential time course of functional regeneration for C-nociceptor sub-types after capsaicin. All sensations recovered completely within 7 weeks in healthy subjects. Our findings contrast analgesia lasting for months in spontaneous neuropathic pain patients treated with 8% capsaicin. Significance Sinusoidal electrical stimulation can still activate small diameter axons desensitized to heat after 4 consecutive days of topical 8% capsaicin application and reveals differential temporal functional regeneration of C-nociceptor sub-types. Electrical sinusoidal stimulation may detect such axons that no longer respond to heat stimuli in neuropathic skin. |
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| Item Description: | Erstmals veröffentlicht: 19. September 2024 Gesehen am 14.01.2025 |
| Physical Description: | Online Resource |
| ISSN: | 1532-2149 |
| DOI: | 10.1002/ejp.4726 |