title: Persistent, comorbid pain and anxiety can be uncoupled in a mouse model.
abstract: Clinically, pain and anxiety frequently coexist; however, these two conditions' interaction is limited and contradictory in animal studies. In this study, we combined social defeat (SD) stress with Freund's adjuvant (CFA)-induced persistent inflammatory pain to investigate the reciprocal relationship between anxiety-like and nociceptive behaviors in two mouse strains. C57BL/6J mice subjected to the 10-day period of SD stress by repeated CD-1 mice aggression exhibited significant social interaction avoidance behaviors in the social interaction (SI) test, which is believed to represent the symptoms of anxiety. These mice also displayed anxiety-like behaviors in elevated plus maze (EPM) and open field (OF) tests. Compared to C57BL/6J mice, FVB/NJNju mice showed less basal social contact, but their behavioral responses to 10-day SD stress were more resilient. CFA-inflammatory mice showed robust mechanical allodynia and thermal hyperalgesia in both strains, but did not develop obvious social avoidance and anxiety-like behaviors 10 days after CFA-inflammation. Interestingly, CFA-inflammatory mice exposed to SD stress were not accompanied by a worsening of pain and anxiety-like behaviors in most tests. In contrast, the SD stress-induced social avoidance was significantly antagonized by combining with CFA-inflammatory pain. These findings suggest that persistent inflammatory pain and SD stress-induced anxiety may not necessarily exacerbate one another in animal models of comorbidity.
authors.affiliation: Institute of Neurobiology, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of Neurobiology, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China; Department of Integrative Medicine and Neurobiology, Shanghai Medical College, Fudan University, Shanghai 200032, China. Electronic address: ribaike@163.com.
authors.forename: Liu
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Integrative Medicine and Neurobiology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Yu
authors.affiliation: Institute of Neurobiology, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China. Electronic address: yuqiuzhang@fudan.edu.cn.
authors.forename: Yu-Qiu
authors.initials: YQ
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001008:Anxiety Disorders / Q000150:complications* / Q000503:physiopathology*; D059350:Chronic Pain / Q000150:complications* / Q000503:physiopathology*; D015897:Comorbidity; D004195:Disease Models, Animal; D004291:Dominance-Subordination; D005106:Exploratory Behavior / Q000502:physiology; D005620:Freund's Adjuvant; D006358:Hot Temperature; D006930:Hyperalgesia / Q000150:complications / Q000503:physiopathology; D008297:Male; D008810:Mice, Inbred C57BL; D059226:Nociceptive Pain / Q000150:complications / Q000503:physiopathology; D055500:Resilience, Psychological; D012720:Severity of Illness Index; D012919:Social Behavior; D013045:Species Specificity; D013315:Stress, Psychological / Q000150:complications / Q000503:physiopathology; D014110:Touch
chemical_list: D005620:Freund's Adjuvant
keywords: Allodynia and hyperalgesia; Anxiety-like behavior; Comorbidity; Inflammatory pain; Social defeat; Social interaction avoidance