title: Role of spinal GABAA receptor reduction induced by stress in rat thermal hyperalgesia.
abstract: The mechanisms underlying stress-induced hyperalgesia (SIH) remain poorly understood. Recent findings have provided strong evidence indicating that SIH could be related, at least in part, to alterations in spinal cord GABA activity. In the present study, we first investigated how acute restraint stress impacted pain responses as assessed using the tail flick immersion test. These results showed that rats developed hyperalgesia at 6 h after being subjected to 1-h acute restraint stress. Second, we measured the activation of spinal neurons and alterations in expression of GABAA receptor β2 and β3 subunits as related to stress-induced hyperalgesia. Results from Western blot and immunofluorescence assays showed that c-fos protein increased in the dorsal horn of the lumbar spinal cord and GABAA receptor β2 and β3 subunit proteins decreased significantly at 6 h after exposure to 1 h of acute restraint stress. Finally, the effects of spinal GABAA receptor alteration on SIH were evaluated. These results showed that intrathecal administration of muscimol inhibited hyperalgesia induced by stress while bicuculline enhanced hyperalgesia in the control groups. Taken together, the present data reveal that GABAA receptor β2 and β3 decrease following 1 h of acute restraint stress and may play a critical role in SIH.
authors.affiliation: Department of Physiology, School of Medicine, Shandong University, Jinan, 250012, People's Republic of China, xuelianma@sdu.edu.cn.
authors.forename: Xuelian
authors.initials: X
authors.lastname: Ma
authors.forename: Weiying
authors.initials: W
authors.lastname: Bao
authors.forename: Xiujun
authors.initials: X
authors.lastname: Wang
authors.forename: Zhilong
authors.initials: Z
authors.lastname: Wang
authors.forename: Qiaoran
authors.initials: Q
authors.lastname: Liu
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Yao
authors.forename: Di
authors.initials: D
authors.lastname: Zhang
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.forename: Shuang
authors.initials: S
authors.lastname: Cui
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D004195:Disease Models, Animal; D058785:GABA-A Receptor Agonists / Q000627:therapeutic use; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006930:Hyperalgesia / Q000150:complications*; D008297:Male; D009118:Muscimol / Q000627:therapeutic use; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D011963:Receptors, GABA-A / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism*; D013315:Stress, Psychological / Q000150:complications* / Q000188:drug therapy / Q000473:pathology*; D013997:Time Factors
chemical_list: D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D016760:Proto-Oncogene Proteins c-fos; D011963:Receptors, GABA-A; D009118:Muscimol; D001640:Bicuculline