The Effect of Optogenetic Inhibition of the Anterior Cingulate Cortex in Neuropathic Pain Following Sciatic Nerve Injury
The Effect of Optogenetic Inhibition of the Anterior Cingulate Cortex in Neuropathic Pain Following Sciatic Nerve Injury
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DOI：
10.1007/s12031-020-01685-7
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发表时间：
2020-08-18
影响因子：
3.1
通讯作者：
Park, Young Seok
中科院分区：
文献类型：
--
作者：
Elina, K. C.;Moon, Hyeong Cheol;Park, Young Seok
皮质去抑制是导致与周围神经损伤相关的神经病理性疼痛的潜在病理改变。神经损伤导致前扣带皮层抑制解除的报道。然而，前扣带皮层（ACC）的光遗传学抑制对神经损伤诱导的神经病理性疼痛的感觉成分的影响还没有得到很好的研究。为了研究光遗传学ACC调节的可行性，我们将光遗传学病毒或无效病毒注射到神经损伤诱导的神经病理性疼痛模型的ACC中。调节单侧ACC，并通过机械和热敏感性测试测量光遗传学效应。在“预照明关闭”、“刺激-黄灯打开”和“照明关闭后”状态下进行评估。损伤模型中ACC的光遗传学抑制揭示了改善的机械和热刺激，对神经损伤诱导的神经性疼痛具有深刻的疼痛缓解作用。在体内电生理记录中的感觉丘脑放电也在激光刺激期间改变。这一发现表明，在神经损伤ACC的过度活跃增加输出到脊髓丘脑束通过直接或间接的途径。ACC神经元的直接光抑制可以在恢复平衡中发挥重要作用，并为减轻周围神经损伤引起的神经病理性疼痛的技术提供新的见解。
Cortical disinhibition is the underlying pathological alteration contributing to neuropathic pain associated with peripheral nerve injury. Nerve injury resulting in disinhibition of the anterior cingulate cortex has been reported. However, the effect of optogenetic inhibition of the anterior cingulate cortex (ACC) on the sensory component of nerve injury-induced neuropathic pain has not been well studied. To investigate the feasibility of optogenetic ACC modulation, we injected an optogenetic virus or a null virus into the ACC of a nerve injury-induced neuropathic pain model. The unilateral ACC was modulated, and the optogenetic effect was measured by mechanical and thermal sensitivity tests. The assessment was performed in "pre-light off," "stimulation-yellow light on," and "post-light off" states. Optogenetic inhibition of the ACC in injury models revealed improved mechanical and thermal latencies with profound pain-relieving effects against nerve injury-induced neuropathic pain. The sensory thalamic discharge in electrophysiological in vivo recordings was also altered during laser stimulation. This finding indicates that hyperactivity of the ACC in nerve injury increases output to the spinothalamic tract through direct or indirect pathways. The direct photoinhibition of ACC neurons could play a vital role in restoring equilibrium and provide novel insight into techniques that can assuage peripheral nerve injury-induced neuropathic pain.