A feed-forward spinal cord glycinergic neural circuit gates mechanical allodynia
A feed-forward spinal cord glycinergic neural circuit gates mechanical allodynia
复制标题
前馈脊髓甘氨酸神经回路控制机械异常性疼痛。
DOI：
10.1172/jci70026
复制
发表时间：
2013-09-01
影响因子：
15.9
通讯作者：
Xiong, Lize
中科院分区：
文献类型：
--
作者：
Lu, Yan;Dong, Hailong;Xiong, Lize
神经性疼痛的特征在于由低阈值有髓鞘A β纤维激活诱导的机械性异常性疼痛。最初的疼痛门理论提出，脊髓背角（DH）板层II中的抑制性中间神经元充当“门控”单元，用于防止无害和伤害性信号之间的相互作用。然而，我们对脊髓DH中疼痛信号和调制的神经元回路的理解是不完整的。使用大鼠模型，我们已经表明，甘氨酸能抑制性和兴奋性A β纤维输入到浅表DH中的PKC γ（+）神经元上的会聚形成前馈抑制回路，其阻止A β输入激活伤害性通路。这种前馈抑制在外周神经损伤或甘氨酸阻断后被抑制，导致通过A β-纤维刺激在伤害性通路中不适当地诱导动作电位输出。此外，脊髓阻断甘氨酸能突触传递在体内引起显着的机械异常性疼痛。我们的研究结果确定了一个甘氨酸前馈抑制电路，作为一个门控分离无害的机械感受性通路和伤害性通路在脊髓DH。在周围神经损伤后，这种甘氨酸能抑制回路的中断有可能引起机械性异常性疼痛，这是神经病理性疼痛的主要症状。
Neuropathic pain is characterized by mechanical allodynia induced by low-threshold myelinated A beta-fiber activation. The original gate theory of pain proposes that inhibitory interneurons in the lamina II of the spinal dorsal horn (DH) act as "gate control" units for preventing the interaction between innocuous and nociceptive signals. However, our understanding of the neuronal circuits underlying pain signaling and modulation in the spinal DH is incomplete. Using a rat model, we have shown that the convergence of glycinergic inhibitory and excitatory A beta-fiber inputs onto PKC gamma(+) neurons in the superficial DH forms a feed-forward inhibitory circuit that prevents A beta input from activating the nociceptive pathway. This feed-forward inhibition was suppressed following peripheral nerve injury or glycine blockage, leading to inappropriate induction of action potential outputs in the nociceptive pathway by A beta-fiber stimulation. Furthermore, spinal blockage of glycinergic synaptic transmission in vivo induced marked mechanical allodynia. Our findings identify a glycinergic feed-forward inhibitory circuit that functions as a gate control to separate the innocuous mechanoreceptive pathway and the nociceptive pathway in the spinal DH. Disruption of this glycinergic inhibitory circuit after peripheral nerve injury has the potential to elicit mechanical allodynia, a cardinal symptom of neuropathic pain.