神经生长因子诱导的 C-神经感受器对人体正弦波电刺激的持续敏感性。

IF 3.4 Q2 NEUROSCIENCES
Pain Reports Pub Date : 2024-09-20 eCollection Date: 2024-10-01 DOI:10.1097/PR9.0000000000001190
Hans Jürgen Solinski, Martin Schmelz, Roman Rukwied
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引用次数: 0

摘要

导言:注射重组人神经生长因子(rhNGF)可引起急性热和长时间的 "多模式"(机械敏感性[CM])和 "无声"(机械不敏感性[CMi])C-痛觉感受器敏化。使用缓慢去极化的正弦波电刺激可不同程度地激活这两类痛觉感受器:目的:探讨rhNGF后人体痛觉感受器对热、机械和电刺激敏感的时间轮廓:将重组人神经生长因子(1 µg)和氯化钠(0.9%)注射到人体前臂皮肤(n = 9,50 µL/次)。注射后第 3、21 和 49 天,除了热痛阈值(HPTs,9 × 9 毫米热电极)和机械冲击痛(4 和 8 米/秒)外,还评估了经皮电刺激(1 毫秒 20 赫兹矩形脉冲、500 毫秒半周期正弦波[1 赫兹]和 4 赫兹正弦波脉冲[2.5 和 60 秒])的疼痛评分(数字评分量表):结果:阈上正弦波刺激特定CM(1赫兹)和联合CM与CMi(4赫兹)激活导致rhNGF后第3天起疼痛加剧,并持续7周。这些时间动态与第 3 天的最小 HPTs(第 49 天恢复正常)或机械冲击痛(第 21 天前发展缓慢,之后根据刺激强度下降)形成鲜明对比。电痛的相关性分析表明,在第3天和第21天评估有或没有同时激活CMi的CM时,其动力学是不同的,而在rhNGF后7周趋于一致:rhNGF对CM和CMi痛觉感受器的超长敏化(通过阈值以上的正弦波电刺激发现)表明,C痛觉感受器的过度兴奋性与信号转导无关,这种过度兴奋性在临床上可能导致rhNGF维持慢性炎症性疼痛。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Sustained nerve growth factor-induced C-nociceptor sensitization to electrical sinusoidal stimulation in humans.

Introduction: Injection of recombinant human nerve growth factor (rhNGF) evokes acute heat and prolonged "polymodal" (mechanosensitive [CM]) and "silent" (mechanoinsensitive [CMi]) C-nociceptor sensitization. Both nociceptor classes can be activated differentially using slowly depolarizing electrical sinusoidal stimuli.

Objectives: To explore the temporal profile of nociceptor sensitization to heat and mechanical and electrical stimuli in humans after rhNGF.

Methods: Recombinant human nerve growth factor (1 µg) and NaCl (0.9%) was injected into human forearm skin (n = 9, 50 µL/injection). Pain ratings (numeric rating scale) to transcutaneous electrical stimuli (1 ms 20 Hz rectangular pulses, 500-ms half-period sine wave [1 Hz] and 4 Hz sine wave pulses [2.5 and 60 seconds]) were assessed at days 3, 21, and 49 after injection, in addition to heat pain thresholds (HPTs, 9 × 9 mm thermode) and mechanical impact pain (4 and 8 m/second).

Results: Suprathreshold sinusoidal stimulation for specific CM (1 Hz) and combined CM and CMi (4 Hz) activation resulted in enhanced pain from day 3 post rhNGF and lasted throughout 7 weeks. These temporal dynamics contrasted minimum HPTs at day 3 (normalized by day 49) or mechanical impact pain (developing slowly until day 21 before declining depending on stimulus intensity). Correlation analyses of electrical pain indicated diverging kinetics when assessed for CM with or without concomitant CMi activation at days 3 and 21, which converged 7 weeks post rhNGF.

Conclusions: Exceptionally long sensitization of CM and CMi nociceptors by rhNGF, uncovered by suprathreshold electrical sinusoidal stimulation, indicates a signal transduction-independent long-lasting hyperexcitability of C-nociceptors that clinically may contribute to rhNGF-maintained chronic inflammatory pain.

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来源期刊
Pain Reports
Pain Reports Medicine-Anesthesiology and Pain Medicine
CiteScore
7.50
自引率
2.10%
发文量
93
审稿时长
8 weeks
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