Regulation and function of spinal and peripheral neuronal B1 bradykinin receptors in inflammatory mechanical hyperalgesia
Regulation and function of spinal and peripheral neuronal B1 bradykinin receptors in inflammatory mechanical hyperalgesia
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DOI：
10.1016/s0304-3959(03)00141-6
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发表时间：
2003-08-01
期刊：
影响因子：
7.4
通讯作者：
Winter, J
中科院分区：
文献类型：
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作者：
Fox, A;Wotherspoon, G;Winter, J
由受损组织释放的激肽激活B-1或B-2缓激肽受体有助于炎性痛觉过敏的发展和维持。B-2激动剂直接激活感觉神经元，而B-1激动剂被认为仅对感觉神经元具有间接作用。最近发现的组成性B-1受体在大鼠神经系统的表达，使我们重新研究神经元B-1受体在炎性痛觉过敏中的作用。因此，我们研究了B-1缓激肽受体调节大鼠背根神经节的炎症性痛觉过敏模型，并将其与痛觉过敏行为。在将弗氏完全佐剂注射到一只后爪中24小时后，在同侧和对侧背根神经节神经元中B-1蛋白表达（通过免疫组织化学测量）显著增加。而轴突切断导致同侧背根神经节中的B-1蛋白减少在行为实验中，B-1 artagonist desArg（10）HOE 140通过鞘内或全身途径给药。在发炎的爪中减弱弗氏完全镇痛剂诱导的机械性痛觉过敏，但不影响机械性异常性疼痛。B-1激动剂desArg（9）BK足底注射给药后不影响未处理大鼠的缩足阈值，而鞘内注射给药引起机械性痛觉过敏。然而，在弗氏完全佐剂诱导的炎症后，desArg（9）BK通过任一途径引起对侧未发炎后爪的显著机械性痛觉过敏，与观察到的对侧和同侧受体水平增加相关。我们的研究结果表明，B-1受体在外周和脊髓中表达的功能作用，在炎症过程中的机械性痛觉过敏。(C)2003年国际疼痛研究协会。由Elsevier Science B. V.出版，版权所有。
Activation of either B-1 or B-2 bradykinin receptors by kinins released from damaged tissues contributes to the development and maintenance of inflammatory hyperalgesia. Whereas B-2 agonists activate sensory neurones directly, B-1 agonists were thought only to have indirect actions on sensory neurones. The recent discovery of constitutive B-1 receptor expression in the rat nervous system lead us to re-investigate the role of neuronal B-1 receptors in inflammatory hyperalgesia. Therefore we have examined B-1 bradykinin receptor regulation in rat dorsal root ganglia in a model of inflammatory hyperalgesia, and correlated it with hyperalgesic behaviour. Twenty-four hours after injection of Freund's complete adjuvant into one hindpaw, there was a significant increase in B-1 protein expression (measured by immunohistochemistry) in both ipsilateral and contralateral dorsal root ganglion neurones. whereas axotomy resulted in reduction of B-1 protein in ipsilateral dorsal root ganglia In behavioural experiments, the B-1 artagonist desArg(10)HOE140, administered by either intrathecal or systemic routes. attenuated Freund's complete adjuvant-induced mechanical hyperalgesia in the inflamed paw, but did not affect mechanical allodynia. The B-1 agonist, desArg(9)BK, did not affect paw withdrawal thresholds in naive rats following intraplantar administration into the paw, whilst intrathecal administration elicited mechanical hyperalgesia. However, after Freund's complete adjuvant-induced inflammation, desArg(9)BK caused a marked mechanical hyperalgesia, by either route, of the contralateral, uninflamed hindpaw, correlating with the observed contralateral and ipsilateral increases in receptor levels. Our results suggest a functional role for B-1 receptors expressed both in the periphery and in the spinal cord, in mechanical hyperalgesia during inflammation. (C) 2003 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.