University of California, Davis, Department of Neurobiology, Physiology and Behavior, 1 Shields Ave., Davis, CA 95616, USA.
J Neurophysiol. 2011 Apr;105(4):1701-10. doi: 10.1152/jn.00922.2010. Epub 2011 Jan 27.
Szechuan peppers contain hydroxy-α-sanshool that imparts desirable tingling, cooling, and numbing sensations. Hydroxy-α-sanshool activates a subset of sensory dorsal root ganglion (DRG) neurons by inhibiting two-pore potassium channels. We presently investigated if a tingle-evoking sanshool analog, isobutylalkenyl amide (IBA), excites rat DRG neurons and, if so, if these neurons are also activated by agonists of TRPM8, TRPA1, and/or TRPV1. Thirty-four percent of DRG neurons tested responded to IBA, with 29% of them also responding to menthol, 29% to cinnamic aldehyde, 66% to capsaicin, and subsets responding to two or more transient receptor potential (TRP) agonists. IBA-responsive cells had similar size distributions regardless of whether they responded to capsaicin or not; cells only responsive to IBA were larger. Responses to repeated application of IBA at a 5-min interstimulus interval exhibited self-desensitization (tachyphylaxis). Capsaicin did not cross-desensitize responses to IBA to any greater extent than the tachyphylaxis observed with repeated IBA applications. These findings are consistent with psychophysical observations that IBA elicits tingle sensation accompanied by pungency and cooling, with self-desensitization but little cross-desensitization by capsaicin. Intraplantar injection of IBA elicited nocifensive responses (paw licking, shaking-flinching, and guarding) in a dose-related manner similar to the effects of intraplantar capsaicin and serotonin. IBA had no effect on thermal sensitivity but enhanced mechanical sensitivity at the highest dose tested. These observations suggest that IBA elicits an unfamiliar aversive sensation that is expressed behaviorally by the limited response repertoire available to the animal.
花椒含有羟基-α-山椒素，赋予其令人愉悦的刺痛、清凉和麻木感。羟基-α-山椒素通过抑制双孔钾通道激活感觉背根神经节 (DRG) 神经元的一个亚群。我们目前研究了一种引起刺痛的山椒素类似物，异丁烯基酰胺（IBA），是否兴奋大鼠 DRG 神经元，如果是，这些神经元是否也被 TRPM8、TRPA1 和/或 TRPV1 的激动剂激活。测试的 34% DRG 神经元对 IBA 有反应，其中 29%对薄荷醇有反应，29%对肉桂醛有反应，66%对辣椒素有反应，亚组对两种或多种瞬时受体电位 (TRP) 激动剂有反应。无论是否对辣椒素有反应，IBA 反应细胞的大小分布相似；仅对 IBA 有反应的细胞更大。在 5 分钟的刺激间隔内重复应用 IBA 时，观察到自脱敏（快速脱敏）。与重复应用 IBA 观察到的快速脱敏相比，辣椒素对 IBA 反应的交叉脱敏作用没有更大程度的增强。这些发现与心理物理观察结果一致，即 IBA 引起刺痛感觉，伴有刺激性和清凉感，具有自脱敏作用，但与辣椒素的交叉脱敏作用很小。IBA 皮内注射以类似于皮内辣椒素和 5-羟色胺的剂量相关方式引起伤害感受反应（舔爪、抖动-退缩和保护）。IBA 对热敏感性没有影响，但在测试的最高剂量下增强了机械敏感性。这些观察结果表明，IBA 引起一种陌生的厌恶感觉，动物通过其有限的反应谱来表现出这种感觉。
