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Compared with wild-type mice,\n            <jats:italic>Comt<\/jats:italic>\n            <jats:sup>+\/\u2212<\/jats:sup>\n            mice undergoing repeated swim stress and molar extraction surgery intervention exhibited pronounced multisite body pain and depressive-like behavior lasting &gt;3 months.\n            <jats:italic>Comt<\/jats:italic>\n            <jats:sup>+\/\u2212<\/jats:sup>\n            mice undergoing the intervention also exhibited enhanced activity of primary afferent nociceptors innervating hindpaw and low back sites and increased plasma concentrations of norepinephrine and pro-inflammatory cytokines interleukin-6 (IL-6) and IL-17A. The pain and depressive-like behavior were of greater magnitude and longer duration (\u226512 months) in females versus males. Furthermore, increases in anxiety-like behavior and IL-6 were female-specific. The effect of COMT genotype \u00d7 stress interactions on pain, IL-6, and IL-17A was validated in a cohort of 549 patients with CPPCs, demonstrating clinical relevance. Last, we assessed the predictive validity of the model for analgesic screening and found that it successfully predicted the lack of efficacy of minocycline and the CB2 agonist GW842166X, which were effective in spared nerve injury and complete Freund\u2019s adjuvant models, respectively, but failed in clinical trials. Yet, pain in the CPPC model was alleviated by the beta-3 adrenergic antagonist SR59230A. Thus, the CPPC mouse model reliably recapitulates clinically and biologically relevant features of CPPCs and may be implemented to test underlying mechanisms and find new therapeutics.\n          <\/jats:p>","DOI":"10.1126\/scitranslmed.adj0395","type":"journal-article","created":{"date-parts":[[2024,4,10]],"date-time":"2024-04-10T17:58:47Z","timestamp":1712771927000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":5,"title":["A mouse model of chronic primary pain that integrates clinically relevant genetic vulnerability, stress, and minor injury"],"prefix":"10.1126","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-2182-7407","authenticated-orcid":true,"given":"Yaomin","family":"Wang","sequence":"first","affiliation":[{"name":"Center for Translational Pain Medicine, Department of Anesthesiology, Duke University School of Medicine, Durham, NC 27710, 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