A role for polymodal C-fiber afferents in nonhistaminergic itch.
A role for polymodal C-fiber afferents in nonhistaminergic itch.
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DOI：
10.1523/jneurosci.1760-08.2008
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发表时间：
2008-07-23
期刊：
影响因子：
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通讯作者：
Ringkamp M
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文献类型：
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作者：
Johanek LM;Meyer RA;Friedman RM;Greenquist KW;Shim B;Borzan J;Hartke T;LaMotte RH;Ringkamp M
最近对人类的心理物理学和电生理学研究表明，存在两种瘙痒的外周途径，一种对组胺有反应，另一种可以被非组胺能瘙痒剂（例如牛针）激活。为了探索非组胺能瘙痒的周围神经元通路，在局部应用牛骨针或皮内注射组胺和辣椒素后，对猴子的无髓鞘传入纤维的行为反应和神经元活性进行了评估。牛肉和组胺（但不是辣椒素）会引起抓挠行为，表明存在瘙痒。在单纤维记录中，将牛黄、组胺和/或辣椒素应用于 43 个机械热敏 C 纤维 (CMH) 伤害感受器的皮肤感受野。大多数 CMH 对牛饲料（43 例中的 39 例）或组胺（38 例中的 29 例）表现出长时间的反应，但对辣椒素（34 例中的 3 例）没有反应。 7 个 CMH 被牛激活，但组胺未被激活。对牛的平均反应是对组胺反应的两倍多，而且反应不相关。 CMH 对阶梯式热刺激（49°C，3 秒）的反应要么是快速适应（QC），要么是缓慢适应（SC）。相比之下，cowhage 反应的特点是爆发两个或多个动作电位（〜1 Hz）。 QC 纤维的总牛犊反应（97 个动作电位/5 分钟）是 SC 纤维（49 个动作电位/5 分钟）的两倍。 QC 纤维的一个子集表现出高频内突发放电（~30 Hz）。这些结果表明 CMH 可能通过多种机制编码牛的瘙痒以及机械和热刺激的疼痛。
Recent psychophysical and electrophysiological studies in humans suggest the existence of two peripheral pathways for itch, one that is responsive to histamine and a second pathway that can be activated by nonhistaminergic pruritogens (e.g., cowhage spicules). To explore the peripheral neuronal pathway for nonhistaminergic itch, behavioral responses and neuronal activity in unmyelinated afferent fibers were assessed in monkey after topical application of cowhage spicules or intradermal injection of histamine and capsaicin. Cowhage and histamine, but not capsaicin, evoked scratching behavior indicating the presence of itch. In single-fiber recordings, cowhage, histamine and/or capsaicin were applied to the cutaneous receptive field of 43 mechano-heat-sensitive C-fiber (CMH) nociceptors. The majority of CMHs exhibited a prolonged response to cowhage (39 of 43) or histamine (29 of 38), but not to capsaicin (3 of 34). Seven CMHs were activated by cowhage but not histamine. The average response to cowhage was more than twice the response to histamine, and responses were not correlated. The response of the CMHs to a stepped heat stimulus (49°C, 3 s) was either quickly adapting (QC) or slowly adapting (SC). In contrast, the cowhage response was characterized by bursts of two or more action potentials (at ∼1 Hz). The total cowhage response of the QC fibers (97 action potentials/5 min) was twice that of the SC fibers (49 action potentials/5 min). A subset of QC fibers exhibited high-frequency intraburst discharges (∼30 Hz). These results suggest multiple mechanisms by which CMHs may encode itch to cowhage as well as pain to mechanical and heat stimuli.