Roles of capsaicin-insensitive nociceptors in cutaneous pain and secondary hyperalgesia
Roles of capsaicin-insensitive nociceptors in cutaneous pain and secondary hyperalgesia
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DOI：
10.1093/brain/124.9.1754
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发表时间：
2001-09-01
期刊：
影响因子：
14.5
通讯作者：
Treede, RD
中科院分区：
文献类型：
--
作者：
Magerl, W;Fuchs, PN;Treede, RD
多模伤害感受器对机械、热和化学刺激作出反应。虽然对热和刺激性物质辣椒素的敏感性最近通过香草受体1型受体离子通道的特性联系在一起，但对有害机械刺激（如临床神经学中使用的针刺）的敏感性似乎无关。我们采用定量心理物理技术，结合神经压迫选择性传导阻滞和局部辣椒素治疗选择性脱敏，研究针刺痛的外周神经基础。通过压迫桡浅神经来完全阻断a纤维（标准：第一痛觉丧失）降低了针刺痛的刺激反应功能（与基线相比-82 +/- 6%）。用10%辣椒素乳膏局部预处理皮肤也降低了针刺刺激反应功能（-32 +/- 10%），而激光引起的热痛完全消除（-96 +/- 2%）。在辣椒素脱敏和a纤维阻断联合治疗下，针刺痛完全消除（-98 +/- 1%）。将40杯辣椒素皮内注射到两个皮肤区域之间的正常皮肤中，这两个皮肤区域已经用辣椒素乳膏或载体预处理过，产生继发性痛觉过敏，两个区域的针刺痛刺激反应功能增强260%。相比之下，轴突反射耀斑仅扩散到车辆处理区域。这些结果表明，辣椒素敏感传入，包括多模态a纤维和c纤维伤害感受器，对针刺痛的贡献很小，辣椒素不敏感的c纤维对机械痛或热痛的贡献都不显著。针刺痛主要由辣椒素不敏感的a纤维伤害感受器介导，包括高阈值机械感受器和I型机械-热伤害感受器。此外，对这些a纤维伤害感受器输入的中枢致敏是继发性痛觉过敏区对点状机械刺激反应增强疼痛的主要机制。这些辣椒素不敏感的a纤维伤害感受器也可能介导神经性疼痛的痛觉过敏。
Polymodal nociceptors respond to mechanical, thermal and chemical stimuli. Whereas sensitivities to heat and to the irritant substance capsaicin have recently been linked via the properties of the vanilloid receptor type 1 receptor ion channel, sensitivity to noxious mechanical stimuli such as the pinpricks used in clinical neurology seems to be unrelated. We investigated the peripheral neural basis of pinprick pain using quantitative psychophysical techniques combined with selective conduction block by nerve compression and selective desensitization by topical capsaicin treatment. Complete A-fibre block by compression of the superficial radial nerve (criterion: loss of first pain sensation) lowered the stimulus-response function for pinprick pain (-82 +/- 6% versus baseline). Topical pretreatment of the skin with a 10% capsaicin cream also lowered the pinprick stimulus-response function (-32 +/- 10%), whereas laser-evoked heat pain was eliminated completely (-96 +/- 2%). Under combined capsaicin desensitization and A-fibre blockade, pinprick pain was eliminated completely (-98 +/- 1%). Intradermal injection of 40 mug capsaicin into normal skin between two skin areas that had been pretreated with either capsaicin cream or vehicle produced secondary hyperalgesia with a 260% enhancement of the stimulus-response function for pinprick pain in both areas. In contrast, axon reflexive flare spread only into the vehicle-treated area. These results suggest that capsaicin-sensitive afferents, including polymodal A-fibre and C-fibre nociceptors, make a small contribution to pinprick pain and that capsaicin-insensitive C-fibres do not contribute significantly to either mechanical or heat pain. Pinprick pain is mediated primarily by capsaicin-insensitive A-fibre nociceptors, which include high-threshold mechanoreceptors and type I mechano-heat nociceptors. In addition, central sensitization to input from these A-fibre nociceptors is the primary mechanism that accounts for the enhanced pain in response to punctate mechanical stimuli in the zone of secondary hyperalgesia. These capsaicin-insensitive A-fibre nociceptors may also mediate hyperalgesia in neuropathic pain.