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Microglia\u2010mediated neuroinflammation is involved in the development of neuropathic pain and anxiodepression pathogenesis. Whether and how microglia are involved in trigeminal neuralgia\u2010induced anxiodepression remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>Unilateral constriction of the infraorbital nerve (CION) was performed to establish trigeminal neuralgia in rat and mouse models. Mechanical allodynia and anxiodepressive\u2010like behaviours were measured. Optogenetic and pharmacological manipulations were employed to investigate the role of hippocampal microglia in anxiety and depression caused by trigeminal neuralgia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>Trigeminal neuralgia activated ipsilateral but not contralateral hippocampal microglia, up\u2010regulated ipsilateral hippocampal ATP and interleukin\u20101\u03b2 (IL\u20101\u03b2) levels, impaired ipsilateral hippocampal long\u2010term potentiation (LTP) and induced anxiodepressive\u2010like behaviours in a time\u2010dependent manner in rodents. Pharmacological or optogenetic inhibition of ipsilateral hippocampal microglia completely blocked trigeminal neuralgia\u2010induced anxiodepressive\u2010like behaviours. Activation of unilateral hippocampal microglia directly elicited an anxiodepressive state and impaired hippocampal LTP. Knockdown of ipsilateral hippocampal P2X7 receptors prevented trigeminal neuralgia\u2010induced microglial activation and anxiodepressive\u2010like behaviours. Furthermore, we demonstrated that microglia\u2010derived IL\u20101\u03b2 mediated microglial activation\u2010induced anxiodepressive\u2010like behaviours and LTP impairment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>These findings suggest that priming of microglia with ATP\/P2X7 receptors in the ipsilateral hippocampus drives pain\u2010related anxiodepressive\u2010like behaviours via IL\u20101\u03b2. An asymmetric role of the bilateral hippocampus in trigeminal neuralgia\u2010induced anxiety and depression was uncovered. The approaches targeting microglia and P2X7 signalling might offer novel therapies for trigeminal neuralgia\u2010related anxiety and depressive disorder.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.15994","type":"journal-article","created":{"date-parts":[[2022,11,29]],"date-time":"2022-11-29T03:08:21Z","timestamp":1669691301000},"page":"1090-1113","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":59,"title":["Asymmetric activation of microglia in the hippocampus drives anxiodepressive consequences of trigeminal neuralgia in rodents"],"prefix":"10.1111","volume":"180","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3236-1129","authenticated-orcid":false,"given":"Li\u2010Qiang","family":"Chen","sequence":"first","affiliation":[{"name":"State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Department of Translational Neuroscience, Jing'an District Centre Hospital of Shanghai, 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