Adenylate cyclase inhibition attenuates neuropathic pain but lacks pre-emptive effects in rats
Adenylate cyclase inhibition attenuates neuropathic pain but lacks pre-emptive effects in rats
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DOI：
10.1007/s12630-009-9149-z
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发表时间：
2009-10-01
期刊：
影响因子：
--
通讯作者：
Lui, Ping-Wing
中科院分区：
文献类型：
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作者：
Liou, Jiin-Tarng;Liu, Fu-Chao;Lui, Ping-Wing
有证据表明环磷酸腺苷（cAMP）的转导参与了伤害性加工。我们之前的研究表明，鞘内注射腺苷酸环化酶抑制剂可减轻大鼠部分坐骨神经结扎（PSNL）引起的触觉异常痛。本研究在慢性神经性疼痛模型中探讨脊髓cAMP转导对伤害性加工的先导性作用。对雄性Sprague-Dawley大鼠进行鞘内插管和PSNL。在PSNL后2小时、3、7和14天评估后爪对机械和热刺激的伤害性反应。评估脊髓鞘内腺苷酸环化酶抑制剂SQ22536 （0.7 μ mol中枢点A L-1，神经结扎前后30 min）的先发制人效果。同时分析了cAMP反应元件结合蛋白（CREB）及其磷酸化蛋白（CREB- ir和p-CREB-IR）在脊髓中的时空表达谱和免疫反应性。结扎前或结扎后鞘内注射SQ22536可显著减轻大鼠1-3天的异常性痛和痛觉过敏。结扎后CREB表达显著升高（P < 0.05），组间差异无统计学意义。结扎前后鞘内注射SQ22536均能部分降低P - creb - ir蛋白表达，尤其是结扎后3天（P < 0.05）。我们的研究结果显示p-CREB的增加与psnl引起的神经性疼痛之间可能存在关联。然而，在手术前使用腺苷酸环化酶抑制剂没有观察到先发制人的效果。
There is evidence that cyclic adenosine monophosphate (cAMP) transduction is involved in nociceptive processing. We previously showed that intrathecal injection of an adenylate cyclase inhibitor attenuated tactile allodynia caused by partial sciatic nerve ligation (PSNL) in rats. The present study investigates the pre-emptive effects of spinal cAMP transduction on nociceptive processing in a chronic neuropathic pain model.Intrathecal catheterization and PSNL were performed in male Sprague-Dawley rats. Nociceptive responses to mechanical and thermal stimuli were evaluated at the hindpaw at 2 hr and at 3, 7, and 14 days after PSNL. The pre-emptive effects of the intrathecal adenylate cyclase inhibitor, SQ22536 (0.7 mu mol center dot A L-1, 30 min before or after nerve ligation) were assessed. Also, the spatial and temporal expression profiles and immunoreactivity in the spinal cord of the cAMP response element binding protein (CREB) and its phosphorylated proteins (CREB-IR and p-CREB-IR) were analyzed.Compared with the rats treated with the vehicle, allodynia and hyperalgesia were significantly attenuated at 1-3 days by the intrathecal injection of SQ22536 performed either before or after ligation. The expression of CREB was significantly higher after ligation (P < 0.05), but differences were not observed between groups. Intrathecal injection of SQ22536, either before or after ligation, partially reduced p-CREB-IR protein expression in comparison with the vehicle control, especially after the first 3 days (P < 0.05).Our results show a possible association between the increase in p-CREB and PSNL-induced neuropathic pain. However, a pre-emptive effect of adenylate cyclase inhibitor administered before surgery was not observed.