Department Anatomy, University California San Francisco, San Francisco, CA, USA.
Department Psychiatry, University California San Francisco, San Francisco, CA, USA.
Brain. 2019 Sep 1;142(9):2655-2669. doi: 10.1093/brain/awz203.
Dysfunction of inhibitory circuits in the rostral anterior cingulate cortex underlies the affective (aversive), but not the sensory-discriminative features (hypersensitivity) of the pain experience. To restore inhibitory controls, we transplanted inhibitory interneuron progenitor cells into the rostral anterior cingulate cortex in a chemotherapy-induced neuropathic pain model. The transplants integrated, exerted a GABA-A mediated inhibition of host pyramidal cells and blocked gabapentin preference (i.e. relieved ongoing pain) in a conditioned place preference paradigm. Surprisingly, pain aversiveness persisted when the transplants populated both the rostral and posterior anterior cingulate cortex. We conclude that selective and long lasting inhibition of the rostral anterior cingulate cortex, in the mouse, has a profound pain relieving effect against nerve injury-induced neuropathic pain. However, the interplay between the rostral and posterior anterior cingulate cortices must be considered when examining circuits that influence ongoing pain and pain aversiveness.
抑制回路在额前扣带回皮质前部的功能障碍是疼痛体验的情感（厌恶）特征的基础，但不是感觉辨别（过敏）特征的基础。为了恢复抑制控制，我们将抑制性中间神经元祖细胞移植到化疗诱导的神经性疼痛模型的额前扣带回皮质中。移植体整合后，对宿主锥体神经元施加 GABA-A 介导的抑制作用，并阻断加巴喷丁偏好（即缓解持续性疼痛）在条件性位置偏好范式中。令人惊讶的是，当移植体同时占据额前扣带回皮质的前部和后部时，疼痛的厌恶感仍然存在。我们得出结论，在小鼠中，选择性和长期抑制额前扣带回皮质对神经损伤诱导的神经性疼痛具有深远的缓解疼痛作用。然而，在研究影响持续性疼痛和疼痛厌恶的回路时，必须考虑额前扣带回皮质的前部和后部之间的相互作用。
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