title: Hippocampal activation of microglia may underlie the shared neurobiology of comorbid posttraumatic stress disorder and chronic pain.
abstract: The high comorbidity rates of posttraumatic stress disorder and chronic pain have been widely reported, but the underlying mechanisms remain unclear. Emerging evidence suggested that an excess of inflammatory immune activities in the hippocampus involved in the progression of both posttraumatic stress disorder and chronic pain. Considering that microglia are substrates underlying the initiation and propagation of the neuroimmune response, we hypothesized that stress-induced activation of hippocampal microglia may contribute to the pathogenesis of posttraumatic stress disorder-pain comorbidity. We showed that rats exposed to single prolonged stress, an established posttraumatic stress disorder model, exhibited persistent mechanical allodynia and anxiety-like behavior, which were accompanied by increased activation of microglia and secretion of pro-inflammatory cytokines in the hippocampus. Correlation analyses showed that hippocampal activation of microglia was significantly correlated with mechanical allodynia and anxiety-like behavior. Our data also showed that both intraperitoneal and intra-hippocampal injection of minocycline suppressed single prolonged stress-induced microglia activation and inflammatory cytokines accumulation in the hippocampus, and attenuated both single prolonged stress-induced mechanical allodynia and anxiety-like behavior. Taken together, the present study suggests that stress-induced microglia activation in the hippocampus may serve as a critical mechanistic link in the comorbid relationship between posttraumatic stress disorder and chronic pain. The novel concept introduces the possibility of cotreating chronic pain and posttraumatic stress disorder.
authors.affiliation: Department of Anesthesiology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China.
authors.forename: Rao
authors.initials: R
authors.lastname: Sun
authors.affiliation: Department of Anesthesiology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China.
authors.forename: Zuoxia
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China.
authors.forename: Yishan
authors.initials: Y
authors.lastname: Lei
authors.affiliation: Department of Anesthesiology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China.
authors.forename: Cui'e
authors.initials: C
authors.lastname: Lu
authors.affiliation: Department of Anesthesiology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Rong
authors.affiliation: Department of Anesthesiology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China.
authors.forename: Yu'e
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Anesthesiology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China mazhengliang1964@nju.edu.cn xiaopinggu@nju.edu.cn.
authors.forename: Zhengliang
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Department of Anesthesiology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Gu
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D059350:Chronic Pain / Q000188:drug therapy; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D006930:Hyperalgesia / Q000188:drug therapy; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D008911:Minocycline / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D013313:Stress Disorders, Post-Traumatic / Q000188:drug therapy; D013312:Stress, Physiological / Q000502:physiology*
chemical_list: D016207:Cytokines; D008911:Minocycline
keywords: Posttraumatic stress disorder; chronic pain; comorbidity; hippocampus; microglia; stress-induced hyperalgesia