Slow depolarizing electrical stimuli reveal differential time courses of nociceptor recovery after prolonged topical capsaicin in human skin

IF 3.5 2区医学 Q1 ANESTHESIOLOGY

European Journal of Pain Pub Date : 2024-09-19 DOI:10.1002/ejp.4726

Divya Tumbala Gutti, Richard Carr, Martin Schmelz, Roman Rukwied

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Abstract

BackgroundWe examined de‐functionalization and temporal functional recovery of C‐nociceptor evoked pain after topical 8% capsaicin applied for 4 consecutive days.MethodsCapsaicin 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.ResultsCapsaicin 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.ConclusionsCapsaicin 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.SignificanceSinusoidal 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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缓慢的去极化电刺激揭示了人体皮肤局部长时间使用辣椒素后痛觉感受器恢复的不同时间过程

背景我们研究了连续 4 天局部使用 8% 的辣椒素后 C-神经感受器诱发疼痛的去功能化和时间功能恢复情况。方法在人体前臂皮肤上贴上辣椒素和安慰剂贴片（n = 14）。在 49 天内，每周记录一次冷、温、热痛阈值、电和热（48°C，5 秒）刺激下的疼痛 NRS 以及轴突反射耀斑。机械和热敏感（"多模态"）痛觉感受器由单次半周期正弦波脉冲（0.5 秒，1 赫兹）激活。机械和热不敏感（"无声"）痛觉感受器由 4 赫兹的正弦波刺激激活。在治疗过程中，对正弦波电刺激的感觉有所减弱，但从未消失。与激活 "多模态 "和 "无声 "痛觉感受器的 4 赫兹 2.5 秒正弦波刺激相比，1 赫兹 "多模态 "痛觉感受器电刺激的疼痛恢复时间更长（35 天对 21 天）。从第 21 天到第 49 天，热痛与安慰剂无关。结论辣椒素可取消末端痛觉末梢的热传导，而对正弦波电刺激敏感的小直径轴突仍可被激活。如前所述，1 赫兹去极化刺激可诱发猝发放电，但辣椒素后的恢复速度比 4 赫兹单脉冲刺激慢。这种恢复上的差异表明，辣椒素作用后，C-感觉器亚型的功能再生时间不同。健康受试者的所有感觉都在 7 周内完全恢复。我们的研究结果与自发性神经病理性疼痛患者接受 8%辣椒素治疗后持续数月的镇痛效果形成了鲜明对比。意义正弦波电刺激在连续 4 天局部应用 8%辣椒素后仍能激活对热脱敏的小直径轴突，并揭示了 C 感觉器亚型的不同时间功能再生过程。正弦波电刺激可检测到神经病理性皮肤中不再对热刺激有反应的轴突。

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来源期刊

European Journal of Pain 医学-临床神经学

CiteScore

7.50

自引率

5.60%

发文量

163

审稿时长

4-8 weeks

期刊介绍： European Journal of Pain (EJP) publishes clinical and basic science research papers relevant to all aspects of pain and its management, including specialties such as anaesthesia, dentistry, neurology and neurosurgery, orthopaedics, palliative care, pharmacology, physiology, psychiatry, psychology and rehabilitation; socio-economic aspects of pain are also covered. Regular sections in the journal are as follows: • Editorials and Commentaries • Position Papers and Guidelines • Reviews • Original Articles • Letters • Bookshelf The journal particularly welcomes clinical trials, which are published on an occasional basis. Research articles are published under the following subject headings: • Neurobiology • Neurology • Experimental Pharmacology • Clinical Pharmacology • Psychology • Behavioural Therapy • Epidemiology • Cancer Pain • Acute Pain • Clinical Trials.