title: Involvement of trigeminal astrocyte activation in masseter hyperalgesia under stress.
abstract: It is commonly accepted that psychological stress contributes to the development of temporomandibular joint disorders, in which chronic orofacial pain is the main symptom. However, the central mechanism underlying the development of these disorders has remained unclear. The current study was performed to determine the involvement of the glia in the trigeminal spinal subnucleus caudalis in stress-induced increases in masseter muscle hyperalgesia in rats. After being subjected to chronic restraint stress, the animals showed decreased body weight gain, behavioral changes and marked masseter allodynia. We also found that astrocytes, but not microglia, in the trigeminal subnucleus caudalis (Vc) were dramatically activated. A further analysis was undertaken to investigate the contribution of the glia; we intrathecally injected l-α-aminoadipate (astrocyte-specific inhibitor) and/or minocycline (microglia-specific inhibitor) into the stressed rats. Our results showed that l-α-aminoadipate (LAA), but not minocycline, could significantly attenuate the mechanical masseter allodynia and behavioral changes induced by restraint stress. In addition, the expression of interleukin-1β (IL-1β) and phosphorylated N-methyl-d-aspartic acid receptor 1 (p-NR1) in the Vc was significantly increased after chronic restraint stress, whereas LAA dramatically inhibited the overexpression of IL-1β and p-NR1. Taken together, these results suggest that activated astrocytes in the Vc may be one of the most important factors in the pathophysiology of masseter hyperalgesia induced by restraint stress and the following overexpression of IL-1β and excessive NMDAR phosphorylation may ultimately contribute to masseter hyperalgesia. Thus, inhibiting spinal astrocytic activation may represent a novel therapeutic strategy for the treatment of orofacial pain induced by stress.
authors: State Key Laboratory of Military Stomatology, Department of General Dentistry & Emergency, School of Stomatology, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, PR China.
authors: Ya-Juan
authors: YJ
authors: Zhao
authors: State Key Laboratory of Military Stomatology, Department of General Dentistry & Emergency, School of Stomatology, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, PR China.
authors: Yang
authors: Y
authors: Liu
authors: State Key Laboratory of Military Stomatology, Department of General Dentistry & Emergency, School of Stomatology, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, PR China.
authors: Qiang
authors: Q
authors: Li
authors: State Key Laboratory of Military Stomatology, Department of General Dentistry & Emergency, School of Stomatology, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, PR China.
authors: Yin-Hua
authors: YH
authors: Zhao
authors: Department of Anatomy, Histology and Embryology & K.K. Leung Brain Research Centre, Preclinical School of Medicine, The Fourth Military Medical University, Xi'an 710032, Shaanxi Province, PR China.
authors: Jian
authors: J
authors: Wang
authors: State Key Laboratory of Military Stomatology, Department of General Dentistry & Emergency, School of Stomatology, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, PR China. Electronic address: zhangmin@fmmu.edu.cn.
authors: Min
authors: M
authors: Zhang
authors: State Key Laboratory of Military Stomatology, Department of General Dentistry & Emergency, School of Stomatology, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, PR China. Electronic address: cyj1229@fmmu.edu.cn.
authors: Yong-Jin
authors: YJ
authors: Chen
mesh_terms: D000272:Adipates / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D001835:Body Weight; D002491:Central Nervous System Agents / Q000494:pharmacology; D002908:Chronic Disease; D004195:Disease Models, Animal; D006930:Hyperalgesia / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D007278:Injections, Spinal; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D008406:Masseter Muscle / Q000503:physiopathology*; D017628:Microglia / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D008911:Minocycline / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D014279:Trigeminal Nucleus, Spinal / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*
chemical_list: D000272:Adipates; D002491:Central Nervous System Agents; C000594089:IL1B protein, rat; D053583:Interleukin-1beta; C409466:NR1 NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D008911:Minocycline
keywords: Chronic restraint stress; Glia; Masseter allodynia; Trigeminal spinal subnucleus caudalis