Biphasic modulation of nociceptive processing by the cyclic AMP-protein kinase A signalling pathway in sheep spinal cord
Biphasic modulation of nociceptive processing by the cyclic AMP-protein kinase A signalling pathway in sheep spinal cord
复制标题
DOI：
10.1016/s0304-3940(01)02063-8
复制
发表时间：
2001-08-31
影响因子：
2.5
通讯作者：
Nolan, AM
中科院分区：
文献类型：
--
作者：
Dolan, S;Nolan, AM
环磷酸腺苷（cAMP）-蛋白激酶A（PKA）转导级联在伤害性加工中的作用已被确定。本研究检查了用cAMP类似物8-溴-cAMP和PKA抑制剂H-89二盐酸盐鞘内处理对6只成年绵羊机械刺激的伤害性阈值的影响，以进一步确定cAMP在脊髓伤害性感受中的作用。用420 nmol 8-Br-cAMP处理引起对伤害性刺激的显著痛觉减退，而10倍高剂量（4.2 μ mol）引起机械性痛觉过敏。这两种行为都被H-89（38-380 nmol）阻断。单独用高剂量H-89（380 nmol）处理显著增加伤害性阈值。这些结果表明，激活cAMP PKA信号通路调节急性伤害性事件在脊髓中的双相方式，并表明，显着的紧张性活动存在于这一途径。(C)Elsevier Science爱尔兰有限公司出版。
A role for the cyclic AMP (CAMP)-protein kinase A (PKA) transduction cascade in nociceptive processing has been identified. This study examined the effects of intrathecal treatment with the cAMP analogue 8-Bromo-cAMP and the PKA inhibitor H-89 dihydrochloride on nociceptive thresholds to mechanical stimulation in six adult sheep to define further the role of cAMP in spinal nociception. Treatment with 420 nmol 8-Br-cAMP induced significant hypoalgesia to noxious stimulation, while a 10-fold higher dose (4.2 mu mol) induced mechanical hyperalgesia. Both of these behaviours were blocked by H-89 (38-380 nmol). Treatment with high dose H-89 (380 nmol) alone significantly increased nociceptive thresholds. These results demonstrate that activation of the cAMP-PKA signalling pathway modulates acute nociceptive events in spinal cord in a biphasic manner, and suggest that significant tonic activity exists in this pathway. (C) 2001 Published by Elsevier Science Ireland Ltd.