Fox A, Wotherspoon G, McNair K, Hudson L, Patel S, Gentry C, Winter J
Novartis Institute for Medical Sciences, 5 Gower Place, London WC1E 6BS, UK.
Pain. 2003 Aug;104(3):683-691. doi: 10.1016/S0304-3959(03)00141-6.
Activation of either B1 or B2 bradykinin receptors by kinins released from damaged tissues contributes to the development and maintenance of inflammatory hyperalgesia. Whereas B2 agonists activate sensory neurones directly, B1 agonists were thought only to have indirect actions on sensory neurones. The recent discovery of constitutive B1 receptor expression in the rat nervous system lead us to re-investigate the role of neuronal B1 receptors in inflammatory hyperalgesia. Therefore we have examined B1 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 B1 protein expression (measured by immunohistochemistry) in both ipsilateral and contralateral dorsal root ganglion neurones, whereas axotomy resulted in reduction of B1 protein in ipsilateral dorsal root ganglia. In behavioural experiments, the B1 antagonist desArg10HOE140, 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 B1 agonist, desArg9BK, did not affect paw withdrawal thresholds in nai;ve rats following intraplantar administration into the paw, whilst intrathecal administration elicited mechanical hyperalgesia. However, after Freund's complete adjuvant-induced inflammation, desArg9BK 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 B1 receptors expressed both in the periphery and in the spinal cord, in mechanical hyperalgesia during inflammation.
受损组织释放的激肽激活B1或B2缓激肽受体，有助于炎症性痛觉过敏的发生和维持。B2激动剂可直接激活感觉神经元，而B1激动剂被认为仅对感觉神经元有间接作用。最近在大鼠神经系统中发现组成型B1受体表达，促使我们重新研究神经元B1受体在炎症性痛觉过敏中的作用。因此，我们在炎症性痛觉过敏模型中研究了大鼠背根神经节中B1缓激肽受体的调节，并将其与痛觉过敏行为相关联。在一侧后爪注射弗氏完全佐剂24小时后，同侧和对侧背根神经节神经元中的B1蛋白表达（通过免疫组织化学测量）均显著增加，而轴突切断导致同侧背根神经节中B1蛋白减少。在行为实验中，通过鞘内或全身途径给予B1拮抗剂desArg10HOE140，可减轻弗氏完全佐剂诱导的炎症爪的机械性痛觉过敏，但不影响机械性异常性疼痛。B1激动剂desArg9BK在足底内注射到爪中后，对未处理大鼠的爪退缩阈值没有影响，而鞘内给药则引起机械性痛觉过敏。然而，在弗氏完全佐剂诱导炎症后，desArg9BK通过任何一种途径都可导致对侧未发炎后爪出现明显的机械性痛觉过敏，这与观察到的受体水平同侧和对侧增加相关。我们的结果表明，外周和脊髓中表达的B1受体在炎症期间的机械性痛觉过敏中发挥功能性作用。
