Taltirelin, a thyrotropin-releasing hormone analog, alleviates mechanical allodynia through activation of descending monoaminergic neurons in persistent inflammatory pain
Taltirelin, a thyrotropin-releasing hormone analog, alleviates mechanical allodynia through activation of descending monoaminergic neurons in persistent inflammatory pain
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DOI：
10.1016/j.brainres.2011.07.065
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发表时间：
2011-09-26
期刊：
影响因子：
2.9
通讯作者：
Ishibashi, Hitoshi
中科院分区：
文献类型：
--
作者：
Eto, Kei;Kim, Sun Kwang;Ishibashi, Hitoshi
据报道，促甲状腺素释放激素（TRH）及其类似物可调节下降的单胺能抑制性神经元，从而产生抗痛觉作用。然而，尚不清楚TRH是否在持续疼痛时发挥抗异动作用。在这里，我们研究了他替雷林（一种稳定的TRH类似物）对后爪注射完全弗氏佐剂引起的炎症性持续性疼痛小鼠的机械异位性疼痛的作用。全身给药1.0 mg/kg他替雷林可显著减轻机械异常性疼痛。这种作用被6-羟多巴胺（6-OHDA）诱导的中枢去甲肾上腺素的消耗所消除。虽然腹腔注射α(1)-肾上腺素受体拮抗剂吡唑嗪没有效果，但腹腔和鞘内注射α(2)-肾上腺素受体拮抗剂育亨宾可以阻止他替雷林的抗异速运动。此外，dl -p-氯苯丙氨酸（PCPA）诱导的5-羟色胺（5-HT）耗竭以及腹腔和鞘内注射5-HT1A受体拮抗剂WAY-100635可阻断他替雷林对异位性痛的作用。这些研究结果表明，他替雷林通过间接激活脊髓α(2)-肾上腺素能和5-HT1A受体，调节降去甲肾上腺素能和血清素能神经元通路，减轻炎症性持续性疼痛中的机械异位性疼痛。(C) 2011 Elsevier B.V.版权所有
Thyrotropin-releasing hormone (TRH) and its analogs have been reported to modulate descending monoaminergic inhibitory neurons, resulting in antinociception. However, it remains unknown whether TRH exerts an antiallodynic effect during persistent pain. Here, we investigated the action of taltirelin, a stable TRH analog, on mechanical allodynia in mice with inflammatory persistent pain induced by an injection of complete Freund's adjuvant into the hindpaw. Systemic administration of 1.0 mg/kg taltirelin markedly reduced mechanical allodynia. This effect was abolished by the 6-hydroxydopamine (6-OHDA)-induced depletion of central noradrenaline. While intraperitoneal injection of the alpha(1)-adrenoceptor antagonist prazosin had no effect, intraperitoneal and intrathecal administration of the alpha(2)-adrenoceptor antagonist yohimbine prevented the antiallodynic action of taltirelin. In addition, DL-p-chlorophenylalanine (PCPA)-induced depletion of serotonin (5-HT) and intraperitoneal and intrathecal injection of the 5-HT1A receptor antagonist WAY-100635 blocked the effect of taltirelin on allodynia. These findings suggest that taltirelin alleviates mechanical allodynia in inflammatory persistent pain by modulating the descending noradrenergic and serotonergic neuronal pathways via indirect activation of spinal alpha(2)-adrenergic and 5-HT1A receptors. (C) 2011 Elsevier B.V. All rights reserved.