The central medial nucleus (CM), a prominent cell group of the intralaminar nuclei (ILN) of the thalamus, and the ventrolateral periaqueductal gray matter (vlPAG) are two major components of the medial pain system. Whether vlPAG and CM are input sources of nociceptive information to the basolateral amygdala (BLA) and whether they are involved in neuropathic pain regulation remain unclear. Clarifying the hierarchical organization of these subcortical nuclei (vlPAG, CM, and BLA) can enhance our understanding on the neural circuits for pain regulation. Behavioral test results showed that a CM lesion made by kainic acid (KA) injection could effectively alleviate mechanical hyperalgesia 4, 6, and 8 days after spared nerve injury (SNI) surgery, with the symptoms returning after 10 days. Morphological studies revealed that: (1) the CM received afferents from vlPAG and sent efferents to BLA, indicating that an indirect vlPAG-CM-BLA pathway exists; (2) such CM-BLA projections were primarily excitatory glutamatergic neurons as revealed by fluorescence in situ hybridization; (3) the fibers originated from the CM-formed close contacts with both excitatory and inhibitory neurons in the BLA; and (4) BLA-projecting CM neurons expressed Fos induced by SNI and formed close contacts with fibers from vlPAG, suggesting that the vlPAG-CM-BLA indirect pathway was activated in neuropathic pain conditions. Finally, the vlPAG-CM-BLA indirect pathway was further confirmed using anterograde and monosynaptic virus tracing investigation. In summary, our present results provide behavioral and morphological evidence that the indirect vlPAG-CM-BLA pathway might be a novel pain pathway involved in neuropathic pain regulation.

中文翻译：

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腹侧前导水管灰色物质-丘脑中内侧核-基底外侧杏仁核途径参与大鼠神经性疼痛调节。

丘脑的层内核（ILN）的一个突出的细胞群，中央内侧核（CM）和腹外侧导水管周围灰质（vlPAG）是内侧疼痛系统的两个主要组成部分。vlPAG和CM是否是基底外侧杏仁核（BLA）的伤害感受信息的输入源，以及它们是否参与神经性疼痛调节尚不清楚。阐明这些皮层下核（vlPAG，CM和BLA）的层次结构可以增进我们对疼痛调节神经回路的了解。行为测试结果表明，海藻酸（KA）注射造成的CM病变可有效缓解神经损伤（SNI）手术后第4、6和8天的机械性痛觉过敏，症状在10天后会恢复。形态学研究表明：（1）CM接收到来自vlPAG的传入并将其发送到BLA，表明存在间接的vlPAG-CM-BLA通路；（2）如通过荧光原位杂交所揭示的，这种CM-BLA投影主要是兴奋性谷氨酸能神经元。（3）纤维起源于BLA中与兴奋性和抑制性神经元形成的CM紧密接触；（4）BLA投射的CM神经元表达SNI诱导的Fos，并且与vlPAG的纤维形成紧密接触，这表明vlPAG-CM-BLA间接途径在神经性疼痛条件下被激活。最后，使用顺行和单突触病毒追踪研究进一步证实了vlPAG-CM-BLA间接途径。综上所述，