Potentiation of spinal α2-adrenoceptor analgesia in rats deficient in TRPV1-expressing afferent neurons
Potentiation of spinal α2-adrenoceptor analgesia in rats deficient in TRPV1-expressing afferent neurons
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DOI：
10.1016/j.neuropharm.2007.03.009
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发表时间：
2007-06-01
影响因子：
4.7
通讯作者：
Pan, Hui-Lin
中科院分区：
文献类型：
--
作者：
Chen, Shao-Rui;Pan, Hao-Min;Pan, Hui-Lin
α(2)-肾上腺素受体（α (2)-ARs）位于初级传入终末和脊髓背角的神经元上。然而，它们对α (2)-AR激动剂的镇痛作用的相对贡献尚不清楚。在这项研究中，我们确定了某些突触前a2-AR在鞘内给药α (2)-AR激动剂可乐定产生的抗感觉作用中的作用。用树脂干扰素（RTX）去除表达trpv1的感觉神经元。鞘内注射可乐定的效果是通过测试爪子对有害机械或热刺激的退缩反应来衡量的。在rtx治疗的大鼠中，脊髓中与trpv1表达末端共表达的α (2A)- ar免疫反应性被消除。然而，脊髓中的a2c- ar免疫反应性变化不大。令人惊讶的是，鞘内给药可乐定使RTX组的机械戒断阈值比给药大鼠高得多。在rtx治疗的大鼠中，可乐定效应的持续时间也显著增加。此外，在载药组中，尽管鞘内注射可乐定使热戒断潜伏期大幅增加，但对机械戒断阈值的影响很小且持续时间较短。这项研究提供了新的信息，脊髓给药α (2)-AR激动剂的抗感觉作用在很大程度上是模态特异性的。表达trpv1的感觉神经元的缺失导致突触前α (2A)- ar的减少，但矛盾的是，它增强了可乐啶对机械伤害感觉的作用。(c) 2007 Elsevier Ltd.版权所有。
The alpha(2)-adrenoceptors (alpha(2)-ARs) are located on primary afferent terminals and on neurons in the spinal cord dorsal horn. However, their relative contribution to the analgesic effect of the alpha(2)-AR agonists is not known. In this study, we determined the role of certain presynaptic a2-ARs in the antinociceptive effect produced by intrathecal administration of the alpha(2)-AR agonist clonidine. TRPV1-expressing sensory neurons were removed by resiniferatoxin (RTX). The effect of intrathecal injection of clonidine was measured by testing the paw withdrawal response to noxious mechanical or heat stimuli. In RTX-treated rats, the alpha(2A)-AR-immunoreactivity co-expressed with TRPV1-expressing terminals in the spinal cord was eliminated. However, the a2c-AR-immunoreactivity in the spinal cord was little changed. Surprisingly, intrathecal administration of clonidine produced a much greater increase in the mechanical withdrawal threshold in RTX- than in vehicle-treated rats. The duration of the clonidine effect was also significantly increased in RTX-treated rats. Furthermore, in the vehicle-treated group, although intrathecal injection of clonidine produced a large increase in the thermal withdrawal latency, it only had a small and short-lasting effect on the mechanical withdrawal threshold. This study provides new information that the antinociceptive effect of spinally administered alpha(2)-AR agonists is largely modality-specific. Loss of TRPV1-expressing sensory neurons leads to a reduction in presynaptic alpha(2A)-ARs but paradoxically potentiates the effect of clonidine on mechano-nociception. (c) 2007 Elsevier Ltd. All rights reserved.