Farzinpour Zahra, Liu An, Cao Peng, Mao Yu, Zhang Zhi, Jin Yan
Department of Anesthesiology and Pain Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
Department of Physiology, School of Basic Medical Sciences, Anhui Medical University, Hefei, China.
Front Cell Neurosci. 2022 Jul 14;16:898346. doi: 10.3389/fncel.2022.898346. eCollection 2022.
Although activation of microglial cells is critical in developing brain disorders, their role in anxiety-like behaviors in pain is still vague. This study indicates that alteration of microglia's neuronal spine engulfment capacity in ventral zona incerta (ZI ) leads to significant pain and anxiety-like behaviors in mice 1-day post-injection of Complete Freud's Adjuvant (CFA1D). Performing whole-cell patch-clamp recordings in GABAergic neurons in the ZI (ZI ) in brain slices, we observed decreased activity in ZIv and reduced frequency of the miniature excitatory postsynaptic currents (mEPSCs) in ZI of CFA1D mice compared with the saline1D mice. Besides, chemogenetic activation of ZI significantly relieved pain and anxiety-like behaviors in CFA1D mice. Conversely, in naïve mice, chemogenetic inhibition of ZI induced pain and anxiety-like behaviors. Interestingly, we found changes in the density and morphology of ZI and increased microglial engulfment of spines in ZI of CFA1D mice. Furthermore, pain sensitization and anxiety-like behaviors were reversed when the ZI of CFA1D-treated mice were chemically inhibited by intra-ZI minocycline injection, accompanied by the recovery of decreased ZI excitability. Conclusively, our results provide novel insights that dysregulation of microglial engulfment capacity encodes maladaptation of ZI , thus promoting the development of anxiety-like behaviors in acute pain.
尽管小胶质细胞的激活在脑部疾病的发生发展中至关重要，但其在疼痛相关焦虑样行为中的作用仍不明确。本研究表明，在注射完全弗氏佐剂后1天（CFA1D），小鼠腹侧未定带（ZI ）中小胶质细胞对神经元棘突的吞噬能力改变会导致显著的疼痛和焦虑样行为。在脑片的ZI （ZI ）中的GABA能神经元上进行全细胞膜片钳记录，我们观察到与注射生理盐水后1天（saline1D）的小鼠相比，CFA1D小鼠的ZIv 活性降低，ZI 中小微小兴奋性突触后电流（mEPSCs）的频率降低。此外，对ZI 进行化学遗传学激活可显著缓解CFA1D小鼠的疼痛和焦虑样行为。相反，在未处理的小鼠中，对ZI 进行化学遗传学抑制会诱发疼痛和焦虑样行为。有趣的是，我们发现CFA1D小鼠的ZI 的密度和形态发生了变化，并且ZI 中棘突的小胶质细胞吞噬增加。此外，通过向ZI 内注射米诺环素对CFA1D处理小鼠的ZI 进行化学抑制时，疼痛敏化和焦虑样行为得到逆转，同时ZI 兴奋性降低的情况也得到恢复。总之，我们的结果提供了新的见解，即小胶质细胞吞噬能力的失调编码了ZI 的适应不良，从而促进了急性疼痛中焦虑样行为的发展。
