PDF(Pubmed)
Abstract：
The medial septum (MS) contributes in pain processing and regulation, especially concerning persistent nociception. However, the role of MS glutamatergic neurons in pain and the underlying neural circuit mechanisms in pain remain poorly understood. In this study, chronic constrictive injury of the sciatic nerve (CCI) surgery was performed to induce thermal and mechanical hyperalgesia in mice. The chemogenetic activation of MS glutamatergic neurons decreased pain thresholds in naïve mice. In contrast, inhibition or ablation of these neurons has improved nociception thresholds in naïve mice and relieved thermal and mechanical hyperalgesia in CCI mice. Anterograde viral tracing revealed that MS glutamatergic neurons had projections to the lateral hypothalamus (LH) and supramammillary nucleus (SuM). We further demonstrated that MS glutamatergic neurons regulate pain thresholds by projecting to LH but not SuM, because the inhibition of MS-LH glutamatergic projections suppressed pain thresholds in CCI and naïve mice, yet, optogenetic activation or inhibition of MS-SuM glutamatergic projections had no effect on pain thresholds in naïve mice. In conclusion, our results reveal that MS glutamatergic neurons play a significant role in regulating pain perception and decipher that MS glutamatergic neurons modulate nociception via projections to LH.
摘要：
内侧隔（MS）有助于疼痛的处理和调节，特别是关于持续性的伤害感受。然而,MS谷氨酸能神经元在疼痛中的作用以及疼痛中潜在的神经回路机制仍然知之甚少。在这项研究中,进行坐骨神经慢性缩窄性损伤（CCI）手术以诱导小鼠的热和机械性痛觉过敏。MS谷氨酸能神经元的化学遗传激活降低了幼稚小鼠的疼痛阈值。相比之下,这些神经元的抑制或消融改善了幼稚小鼠的伤害性感受阈值,缓解了CCI小鼠的热痛觉和机械性痛觉过敏.顺行病毒追踪显示，MS谷氨酸能神经元向下丘脑外侧（LH）和哺乳动物上核（SuM）投射。我们进一步证明，MS谷氨酸能神经元通过投射到LH而不是SuM来调节疼痛阈值，因为抑制MS-LH谷氨酸能投射抑制了CCI和幼稚小鼠的疼痛阈值，然而，MS-SuM谷氨酸能投射的光遗传学激活或抑制对幼稚小鼠的疼痛阈值没有影响。总之,我们的结果表明，MS谷氨酸能神经元在调节疼痛感知中起重要作用，并破译MS谷氨酸能神经元通过投射LH调节伤害感受。
