外周5-羟色胺2A受体：治疗慢性炎性痛及神经病理性痛的重要靶点
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摘要
慢性炎性痛及神经病理性痛是临床上常见的症状。过去的研究已证实外周5-HT_(2A)受体在炎性痛中有重要的作用。但是对于外周5-HT_(2A)受体是否也参与骨骼肌肉综合症(muscle-skeletal syndrom)引起的慢性疼痛及神经病理性痛尚不清楚。我们通过在大鼠深层组织膝关节和腓肠肌注射角叉菜胶,以及结扎L5脊神经的方法建立了三种病理性痛模型,探讨外周5-HT_(2A)受体在它们发病机制中的作用。而且,我们也研究了全身注射5-HT_(2A)受体拮抗剂能减轻病理性痛行为的可能机制。
行为学结果显示,阻断外周5-HT_(2A)受体能够明显抑制慢性炎症及神经病理性痛引发的热痛觉过敏。运用免疫组织化学方法进一步发现,在神经病理性痛状态下,背根神经节(Dosal Root Ganglion,DRG)中nNOS(神经元型一氧化氮合酶)和CGRP(降钙素基因相关蛋白)的表达显著增加。而且全身注射5-HT_(2A)受体选择性拮抗剂酮色林能明显削弱它们的表达。这些结果表明,外周5-HT_(2A)受体参与了肌肉骨骼系统炎性痛及神经病理性疼痛,并且对神经病理性痛的调节是通过增加背根神经节中的nNOS和CGRP的释放或表达实现的。
我们的研究证明了全身注射酮色林能够治疗肌肉骨骼痛及神经病理性痛,为临床治疗提供了新的方法。
Chronic inflammatory pain and neuropathic pain are common clinical disorders.It has been documented in the literature that peripheral 5-HT_(2A)receptors play an important role in inflammatory pain.However,it is not clear whether peripheral 5-HT_(2A)receptors contribute to the induction of muscleskeletal pain syndrome and neuropathic pain.We established three pain models by injecting carrageenan into the knee and gastrocnemius and ligating the L5 spinal nerve,respectively,to explore the role of peripheral 5-HT_(2A)receptors in their pathogenesis. Furthermore,we also examined the feasibile mechanisms of systemic injectin of 5-HT_(2A)receptor antagonist to relieve the symptoms in these disorders.
The behavior results showed that blocking peripheral 5-HT_(2A)receptors inhibited the thermal hyperalgesia in inflammatory and neuropathic pain.We further found by immunocytochemical technique that the expressions of nNOS and CGRP in the dorsal root ganglia increased in neuropathic pain,and that the increases were greatly attenuated by systemic injection of 5-HT_(2A)receptor antagonist ketanserin.These results indicate that the activation of peripheral 5-HT_(2A)receptors is involved in pathogenesis of muscleskeletal pain syndrome and neuropathic pain and the involvement is mediated by increasing the synthesis or release of nNOS and CGRP.
Our study also demonstrates that it is possible to treat muscleskeletal pain syndrome and neuropathic pain by systemic injection of ketanserin,providing a new therapy for the clinical disorders.
行为学结果显示,阻断外周5-HT_(2A)受体能够明显抑制慢性炎症及神经病理性痛引发的热痛觉过敏。运用免疫组织化学方法进一步发现,在神经病理性痛状态下,背根神经节(Dosal Root Ganglion,DRG)中nNOS(神经元型一氧化氮合酶)和CGRP(降钙素基因相关蛋白)的表达显著增加。而且全身注射5-HT_(2A)受体选择性拮抗剂酮色林能明显削弱它们的表达。这些结果表明,外周5-HT_(2A)受体参与了肌肉骨骼系统炎性痛及神经病理性疼痛,并且对神经病理性痛的调节是通过增加背根神经节中的nNOS和CGRP的释放或表达实现的。
我们的研究证明了全身注射酮色林能够治疗肌肉骨骼痛及神经病理性痛,为临床治疗提供了新的方法。
Chronic inflammatory pain and neuropathic pain are common clinical disorders.It has been documented in the literature that peripheral 5-HT_(2A)receptors play an important role in inflammatory pain.However,it is not clear whether peripheral 5-HT_(2A)receptors contribute to the induction of muscleskeletal pain syndrome and neuropathic pain.We established three pain models by injecting carrageenan into the knee and gastrocnemius and ligating the L5 spinal nerve,respectively,to explore the role of peripheral 5-HT_(2A)receptors in their pathogenesis. Furthermore,we also examined the feasibile mechanisms of systemic injectin of 5-HT_(2A)receptor antagonist to relieve the symptoms in these disorders.
The behavior results showed that blocking peripheral 5-HT_(2A)receptors inhibited the thermal hyperalgesia in inflammatory and neuropathic pain.We further found by immunocytochemical technique that the expressions of nNOS and CGRP in the dorsal root ganglia increased in neuropathic pain,and that the increases were greatly attenuated by systemic injection of 5-HT_(2A)receptor antagonist ketanserin.These results indicate that the activation of peripheral 5-HT_(2A)receptors is involved in pathogenesis of muscleskeletal pain syndrome and neuropathic pain and the involvement is mediated by increasing the synthesis or release of nNOS and CGRP.
Our study also demonstrates that it is possible to treat muscleskeletal pain syndrome and neuropathic pain by systemic injection of ketanserin,providing a new therapy for the clinical disorders.
引文
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