Department of Rehabilitation, Daping Hospital, Army Medical University, Chongqing, 400042, China.
Army 953 Hospital, Army Medical University, Shigatse, 857000, China.
Neurosci Bull. 2022 Sep;38(9):1041-1056. doi: 10.1007/s12264-022-00892-z. Epub 2022 Jun 15.
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), 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. 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.
从外侧缰核到齿状回（LEC-DG）的突触传递功能变化被认为是疼痛慢性化的原因。然而，投射到 DG 的 LEC 中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）诱导的炎症性疼痛大鼠模型研究了可能的机制。我们发现超极化激活/环核苷酸门控电流（I）显著增加，导致 CFA 切片中 LEC 扇形细胞的过度兴奋。这种现象在 CFA 切片中被激活多巴胺 D2 受体，但不是 D1 受体所减弱。腹侧被盖区-LEC 投射的化学遗传激活具有 D2 受体依赖性的镇痛作用。LEC 内微注射 D2 受体激动剂也抑制了 CFA 诱导的行为性过敏，而这种效应被 I 的预先激活所减弱。我们的研究结果表明，通过激活多巴胺 D2 受体下调 LEC 扇形细胞的兴奋性可能是治疗慢性炎症性疼痛的一种策略。
