Bradykinin enhances AMPA and NMDA receptor activity in spinal cord dorsal horn neurons by activating multiple kinases to produce pain hypersensitivity
Bradykinin enhances AMPA and NMDA receptor activity in spinal cord dorsal horn neurons by activating multiple kinases to produce pain hypersensitivity
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DOI：
10.1523/jneurosci.5349-07.2008
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发表时间：
2008-04-01
影响因子：
5.3
通讯作者：
Woolf, Clifford J.
中科院分区：
文献类型：
--
作者：
Kohno, Tatsuro;Wang, Haibin;Woolf, Clifford J.
缓激肽通过突触前和突触后B-2受体增强突触谷氨酸在脊髓中的释放和作用，从而促进活动依赖的中枢敏化和疼痛超敏(Wang等，2005)。我们现在已经研究了负责缓激肽对浅层背角神经元谷氨酸能作用和传递的突触后调制作用的信号通路。在背角神经元中，B-2受体与蛋白激酶A(PKA)和蛋白激酶C(PKC)的Delta亚型共表达，我们发现缓激肽对膜II神经元AMPA和NMDA受体介导的电流的增强需要PKC和PKA的共同激活。PKA的激活位于COX1(环氧合酶-1)的下游。细胞外信号调节激酶(ERK)在PKC和PKA共激活后被激活，鞘内注射缓激肽可在体内诱导热痛敏，这种作用可通过抑制ERK、PKA和PKC而减轻。我们的结论是，缓激肽通过激活背角神经元中的多个激酶，增强谷氨酸能突触传递，产生疼痛超敏。
Bradykinin potentiates synaptic glutamate release and action in the spinal cord via presynaptic and postsynaptic B-2 receptors, contributing thereby to activity-dependent central sensitization and pain hypersensitivity (Wang et al., 2005). We have now examined the signaling pathways that are responsible for the postsynaptic modulatory actions of bradykinin on glutamatergic action and transmission in superficial dorsal horn neurons. B-2 receptors are coexpressed in dorsal horn neurons with protein kinase A(PKA) and the delta isoform of protein kinase C (PKC), and we find that the augmentation by bradykinin of AMPA and NMDA receptor-mediated currents in lamina II neurons requires coactivation of both PKC and PKA. The activation of PKA is downstream of COX1 (cyclooxygenase-1). Extracellular signal-regulated kinase (ERK) activation is involved after the PKC and PKA coactivation, and intrathecal administration of bradykinin induces a thermal hyperalgesia in vivo, which is reduced by inhibition of ERK, PKA, and PKC. We conclude that bradykinin, by activating multiple kinases in dorsal horn neurons, potentiates glutamatergic synaptic transmission to produce pain hypersensitivity.