Opioids are widely used, effective analgesics to manage severe acute and chronic pain, although they have recently come under scrutiny because of epidemic levels of abuse. While these compounds act on numerous central and peripheral pain pathways, the neuroanatomical substrate for opioid analgesia is not fully understood. By means of single-cell transcriptomics and manipulation of morphine-responsive neurons, we have identified an ensemble of neurons in the rostral ventromedial medulla (RVM) that regulates mechanical nociception in mice. Among these, forced activation or silencing of excitatory RVM BDNF projection neurons mimicked or completely reversed morphine-induced mechanical antinociception, respectively, via a brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB)–dependent mechanism and activation of inhibitory spinal galanin-positive neurons. Our results reveal a specific RVM-spinal circuit that scales mechanical nociception whose function confers the antinociceptive properties of morphine.

中文翻译：

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调节机械镇痛的吗啡反应神经元


阿片类药物是广泛使用的有效镇痛药，用于治疗严重的急性和慢性疼痛，尽管最近由于滥用程度的流行而受到密切关注。虽然这些化合物作用于许多中枢和外周疼痛通路，但阿片类镇痛的神经解剖学基础尚不完全清楚。通过单细胞转录组学和吗啡反应神经元的操作，我们鉴定了延髓头端腹内侧（RVM）中调节小鼠机械伤害感受的神经元群。其中，兴奋性 RVM BDNF 投射神经元的强制激活或沉默分别通过脑源性神经营养因子 (BDNF)/原肌球蛋白受体激酶 B (TrkB) 依赖性机制和抑制性激活来模拟或完全逆转吗啡诱导的机械性镇痛作用。脊髓甘丙肽阳性神经元。我们的结果揭示了一种特定的 RVM 脊髓回路，可以调节机械伤害感受，其功能赋予吗啡的抗伤害特性。