Activation of Dopamine D2 Receptors Alleviates Neuronal Hyperexcitability in the Lateral Entorhinal Cortex via Inhibition of HCN Current in a Rat Model of Chronic Inflammatory Pain
Activation of Dopamine D2 Receptors Alleviates Neuronal Hyperexcitability in the Lateral Entorhinal Cortex via Inhibition of HCN Current in a Rat Model of Chronic Inflammatory Pain
复制标题
在慢性炎性疼痛大鼠模型中，多巴胺 D2 受体的激活通过抑制 HCN 电流减轻外侧内嗅皮层神经元的过度兴奋。
DOI：
10.1007/s12264-022-00892-z
复制
发表时间：
2022-06-15
影响因子：
5.6
通讯作者：
Gao, Chang-Yue
中科院分区：
文献类型：
--
作者：
Gao, Shi-Hao;Tao, Yong;Gao, Chang-Yue
从外侧内嗅皮层到齿状回(LEC-DG)的突触传递的功能变化被认为是导致疼痛时代化的原因。然而，LEC中投射到DG的主要神经元--扇形细胞的潜在变化仍然难以捉摸。在这里，我们使用完全弗氏佐剂(CFA)诱导的炎性疼痛的大鼠模型来研究可能的机制。我们发现超极化激活/环核苷酸门控电流(I-h)显著增加，从而导致CFA脑片LEC扇形细胞的超兴奋性。在CFA脑片中，这种现象通过激活多巴胺D2受体而不是D1受体来减弱。腹侧被盖区-LEC投射的化学激活具有D2受体依赖的镇痛效应。LEC内微量注射D2受体激动剂也可抑制CFA诱导的行为超敏反应，这种作用可被预先激活的i-h区减弱。我们的发现表明，通过激活多巴胺D2受体来下调LEC Fan细胞的兴奋性可能是治疗慢性炎症性疼痛的一种策略。
Functional changes in synaptic transmission from the lateral entorhinal cortex to the dentate gyrus (LEC-DG) are considered responsible for the chronification of pain. However, the underlying alterations in fan cells, which are the predominant neurons in the LEC that project to the DG, remain elusive. Here, we investigated possible mechanisms using a rat model of complete Freund's adjuvant (CFA)-induced inflammatory pain. We found a substantial increase in hyperpolarization-activated/cyclic nucleotide-gated currents (I-h), which led to the hyperexcitability of LEC fan cells of CFA slices. This phenomenon was attenuated in CFA slices by activating dopamine D2, but not D1, receptors. Chemogenetic activation of the ventral tegmental area -LEC projection had a D2 receptor-dependent analgesic effect. Intra-LEC microinjection of a D2 receptor agonist also suppressed CFA-induced behavioral hypersensitivity, and this effect was attenuated by pre-activation of the I-h. Our findings suggest that down-regulating the excitability of LEC fan cells through activation of the dopamine D2 receptor may be a strategy for treating chronic inflammatory pain.