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The basolateral amygdala (BLA) is critically involved in both pain and anxiety processing. Microglia have emerged as key regulators of neuronal plasticity, and disruption of homeostatic neuron\u2013microglia crosstalk can precipitate neuropsychiatric disorders. Although microglia are abundant in the BLA, their specific role in modulating neuronal plasticity underlying pain\u2010induced anxiety remains poorly understood. Here, we demonstrate that spared nerve injury (SNI) induces anxiety\u2010like behaviors in mice, accompanied by neuronal hyperexcitability and increased spine density in the BLA. These changes correlated with increased density of hyper\u2010ramified microglia, along with upregulated P2ry12 expression and enhanced microglial BDNF production. Importantly, microglial P2ry12 knockdown significantly attenuated both process hyper\u2010ramification and BDNF overexpression in the BLA. Furthermore, either microglial depletion with clodronate or microglial P2ry12 knockdown in the BLA reversed neuronal hyperexcitability and spine overgrowth, and alleviated pain and anxiety\u2010like behaviors in SNI mice. Meanwhile, clodronate mildly suppressed neuronal excitability and dendritic spine density in the BLA of control mice, whereas P2ry12 knockdown had no detectable impact on these neuronal measures. Together, these findings support a role for microglia in maintaining physiological neuronal excitability and spine density. Highly\u2010ramified microglia and their increased P2ry12 expression underlie the enhanced neuronal excitability and spine density in the BLA, thereby promoting comorbidity of pain and anxiety.<\/jats:p>","DOI":"10.1002\/glia.70196","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T11:02:14Z","timestamp":1783594934000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Microglial P2ry12 in the Basolateral Amygdala Underlies Neuropathic Pain\u2010Induced Anxiety"],"prefix":"10.1002","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-4250-9626","authenticated-orcid":false,"given":"Xiaohui","family":"Yang","sequence":"first","affiliation":[{"name":"NHC Key Laboratory of Chronobiology Sichuan University  Chengdu China"},{"name":"Joint Laboratory of Pulmonary Development and Related Diseases, West China Second University Hospital Sichuan University  Chengdu 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