Spinal mechanisms of NPY analgesia
Spinal mechanisms of NPY analgesia
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DOI：
10.1016/j.peptides.2006.09.029
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发表时间：
2007-02-01
期刊：
影响因子：
3
通讯作者：
Taylor, Bradley K.
中科院分区：
文献类型：
--
作者：
Smith, Peter A.;Moran, Timothy D.;Taylor, Bradley K.
我们回顾了以前发表的数据，并提出了一些新的数据，表明脊髓应用神经肽Y（NPY）减少急性和慢性疼痛的行为和神经生理学体征。在急性疼痛模型中，早期行为研究表明，脊髓（鞘内）给予NPY和Y2受体激动剂可降低热伤害感受。随后的神经生理学研究表明，Y2介导的抑制兴奋性神经递质释放的初级传入终末在胶状质可能有助于抗伤害性的作用。与急性疼痛一样，NPY减少了炎性疼痛的行为体征，如机械异常性疼痛和热痛觉过敏;然而，受体拮抗剂研究表明脊髓Y1而不是Y2受体的重要贡献。有趣的是，Y1激动剂抑制背角神经元中的抑制性突触事件（事实上，众所周知的L-阿片类镇痛药物产生类似的细胞作用）。为了解决行为和神经生理学数据，我们提出，NPY/Y1抑制脊髓释放的抑制性神经递质（GABA和甘氨酸）到抑制性神经元，例如解除抑制疼痛抑制，导致反射减退。上述Y1和Y2介导的镇痛机制也可能在外周神经损伤的情况下起作用，新的数据表明，NPY剂量依赖性地抑制神经性疼痛的行为体征。事实上，神经生理学研究表明，Y2介导的抑制钙通道电流在背根神经节神经元轴突切断后，实际上是增加。我们的结论是，脊髓交付的Y1激动剂可能是用于治疗慢性炎性疼痛，并使用Y1和Y2激动剂在神经性疼痛值得进一步考虑。(c)2006年爱思唯尔公司All rights reserved.
We review previously published data, and present some new data, indicating that spinal application of neuropeptide Y (NPY) reduces behavioral and neurophysiological signs of acute and chronic pain. In models of acute pain, early behavioral studies showed that spinal (intrathecal) administration of NPY and Y2 receptor agonists decrease thermal nociception. Subsequent neurophysiological studies indicated that Y2-mediated inhibition of excitatory neurotransmitter release from primary afferent terminals in the substantia gelatinosa may contribute to the antinociceptive actions of NPY. As with acute pain, NPY reduced behavioral signs of inflammatory pain such as mechanical allodynia and thermal hyperalgesia; however, receptor antagonist studies indicate an important contribution of spinal Y1 rather than Y2 receptors. Interestingly, Y1 agonists suppress inhibitory synaptic events in dorsal horn neurons (indeed, well known L-opioid analgesic drugs produce similar cellular actions). To resolve the behavioral and neurophysiological data, we propose that NPY/Y1 inhibits the spinal release of inhibitory neurotransmitters (GABA and glycine) onto inhibitory neurons, e.g. disinhibition of pain inhibition, resulting in hyporeflexia. The above mechanisms of Y1- and Y2-mediated analgesia may also operate in the setting of peripheral nerve injury, and new data indicate that NPY dose-dependently inhibits behavioral signs of neuropathic pain. Indeed, neurophysiological studies indicate that Y2-mediated inhibition of Ca2+ channel currents in dorsal root ganglion neurons is actually increased after axotomy. We conclude that spinal delivery of Y1 agonists may be of use in the treatment of chronic inflammatory pain, and that the use of Y1 and Y2 agonists in neuropathic pain warrants further consideration. (c) 2006 Elsevier Inc. All rights reserved.