Loss of cortical control over the descending pain modulatory system determines the development of the neuropathic pain state in rats.
Loss of cortical control over the descending pain modulatory system determines the development of the neuropathic pain state in rats.
复制标题
DOI：
10.7554/elife.65156
复制
发表时间：
2021-02-08
期刊：
影响因子：
7.7
通讯作者：
Pickering AE
中科院分区：
文献类型：
--
作者：
Drake RA;Steel KA;Apps R;Lumb BM;Pickering AE
下行抑制控制的丧失被认为对慢性疼痛的发展至关重要，但导致这种功能丧失的原因尚不清楚。我们已经调查了动态贡献的前边缘皮层神经元预测的导水管周围灰质（PrL-P）的发展神经病理性疼痛的大鼠使用相结合的光学和化学方法。我们发现PrL-P神经元对未受伤动物的热退缩阈值施加紧张性抑制控制。神经损伤后，持续活动的PrL-P神经元掩盖了潜在的超敏反应和改善情感状态。然而，随着感觉超敏反应的出现，这种功能丧失。尽管这种紧张性控制的损失，在损伤后较晚的时间点的PrL-P神经元的光激活可以通过抑制脊髓伤害性处理来恢复抗异常性疼痛的作用。我们认为，皮质驱动下降的疼痛调节系统的损失支持神经损伤后的神经病理性敏化的表达。
The loss of descending inhibitory control is thought critical to the development of chronic pain but what causes this loss in function is not well understood. We have investigated the dynamic contribution of prelimbic cortical neuronal projections to the periaqueductal grey (PrL-P) to the development of neuropathic pain in rats using combined opto- and chemogenetic approaches. We found PrL-P neurons to exert a tonic inhibitory control on thermal withdrawal thresholds in uninjured animals. Following nerve injury, ongoing activity in PrL-P neurons masked latent hypersensitivity and improved affective state. However, this function is lost as the development of sensory hypersensitivity emerges. Despite this loss of tonic control, opto-activation of PrL-P neurons at late post-injury timepoints could restore the anti-allodynic effects by inhibition of spinal nociceptive processing. We suggest that the loss of cortical drive to the descending pain modulatory system underpins the expression of neuropathic sensitisation after nerve injury.