Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital (MGH), Harvard Medical School, Boston, Massachusetts, USA.
McGovern Institute for Brain Research and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
J Clin Invest. 2023 Mar 1;133(5):e166408. doi: 10.1172/JCI166408.
Cortical neural dynamics mediate information processing for the cerebral cortex, which is implicated in fundamental biological processes such as vision and olfaction, in addition to neurological and psychiatric diseases. Spontaneous pain is a key feature of human neuropathic pain. Whether spontaneous pain pushes the cortical network into an aberrant state and, if so, whether it can be brought back to a "normal" operating range to ameliorate pain are unknown. Using a clinically relevant mouse model of neuropathic pain with spontaneous pain-like behavior, we report that orofacial spontaneous pain activated a specific area within the primary somatosensory cortex (S1), displaying synchronized neural dynamics revealed by intravital two-photon calcium imaging. This synchronization was underpinned by local GABAergic interneuron hypoactivity. Pain-induced cortical synchronization could be attenuated by manipulating local S1 networks or clinically effective pain therapies. Specifically, both chemogenetic inhibition of pain-related c-Fos-expressing neurons and selective activation of GABAergic interneurons significantly attenuated S1 synchronization. Clinically effective pain therapies including carbamazepine and nerve root decompression could also dampen S1 synchronization. More important, restoring a "normal" range of neural dynamics through attenuation of pain-induced S1 synchronization alleviated pain-like behavior. These results suggest that spontaneous pain pushed the S1 regional network into a synchronized state, whereas reversal of this synchronization alleviated pain.
皮层神经动力学介导了大脑皮层的信息处理，这与视觉和嗅觉等基本生物过程以及神经和精神疾病有关。自发性疼痛是人类神经性疼痛的一个主要特征。自发性疼痛是否会将皮层网络推向异常状态，如果是，是否可以将其恢复到“正常”工作范围以减轻疼痛，目前尚不清楚。我们使用一种具有自发性疼痛样行为的临床相关的神经性疼痛小鼠模型，报告称口腔自发性疼痛激活了初级体感皮层（S1）内的一个特定区域，通过活体双光子钙成像显示出同步的神经动力学。这种同步性是由局部 GABA 能中间神经元活动减少所支撑的。通过操纵局部 S1 网络或临床有效的疼痛治疗，可以减轻疼痛引起的皮层同步。具体来说，疼痛相关 c-Fos 表达神经元的化学遗传抑制和 GABA 能中间神经元的选择性激活都显著减轻了 S1 的同步。临床有效的疼痛治疗，包括卡马西平和神经根减压，也可以抑制 S1 同步。更重要的是，通过减轻疼痛引起的 S1 同步来恢复“正常”的神经动力学范围，可以缓解疼痛样行为。这些结果表明，自发性疼痛将 S1 区域网络推向同步状态，而逆转这种同步性可以缓解疼痛。
