title: Ethanol Increases Mechanical Pain Sensitivity in Rats via Activation of GABAA Receptors in Medial Prefrontal Cortex.
abstract: Ethanol is widely known for its ability to cause dramatic changes in emotion, social cognition, and behavior following systemic administration in humans. Human neuroimaging studies suggest that alcohol dependence and chronic pain may share common mechanisms through amygdala-medial prefrontal cortex (mPFC) interactions. However, whether acute administration of ethanol in the mPFC can modulate pain perception is unknown. Here we showed that bilateral microinjections of ethanol into the prelimbic and infralimbic areas of the mPFC lowered the bilateral mechanical pain threshold for 48 h without influencing thermal pain sensitivity in adult rats. However, bilateral microinjections of artificial cerebrospinal fluid into the mPFC or bilateral microinjections of ethanol into the dorsolateral PFC (also termed as motor cortex area 1 in Paxinos and Watson's atlas of The Rat Brain. Elsevier Academic Press, Amsterdam, 2005) failed to do so, suggesting regional selectivity of the effects of ethanol. Moreover, bilateral microinjections of ethanol did not change the expression of either pro-apoptotic (caspase-3 and Bax) or anti-apoptotic (Bcl-2) proteins, suggesting that the dose was safe and validating the method used in the current study. To determine whether γ-aminobutyric acid A (GABAA) receptors are involved in mediating the ethanol effects, muscimol, a selective GABAA receptor agonist, or bicuculline, a selective GABAA receptor antagonist, was administered alone or co-administered with ethanol through the same route into the bilateral mPFC. The results showed that muscimol mimicked the effects of ethanol while bicuculline completely reversed the effects of ethanol and muscimol. In conclusion, ethanol increases mechanical pain sensitivity through activation of GABAA receptors in the mPFC of rats.
authors.affiliation: Institute for Biomedical Sciences of Pain and Institute for Functional Brain Disorders, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.
authors.forename: Kai-Wen
authors.initials: KW
authors.lastname: Geng
authors.affiliation: Institute for Biomedical Sciences of Pain and Institute for Functional Brain Disorders, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.
authors.forename: Ting
authors.initials: T
authors.lastname: He
authors.affiliation: Institute for Biomedical Sciences of Pain and Institute for Functional Brain Disorders, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.|Key Laboratory of Brain Stress and Behavior, People's Liberation Army, Xi'an, 710038, China.
authors.forename: Rui-Rui
authors.initials: RR
authors.lastname: Wang
authors.affiliation: Institute for Biomedical Sciences of Pain and Institute for Functional Brain Disorders, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.|Key Laboratory of Brain Stress and Behavior, People's Liberation Army, Xi'an, 710038, China.
authors.forename: Chun-Li
authors.initials: CL
authors.lastname: Li
authors.affiliation: Institute for Biomedical Sciences of Pain and Institute for Functional Brain Disorders, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.
authors.forename: Wen-Jun
authors.initials: WJ
authors.lastname: Luo
authors.affiliation: Institute for Biomedical Sciences of Pain and Institute for Functional Brain Disorders, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.
authors.forename: Fang-Fang
authors.initials: FF
authors.lastname: Wu
authors.affiliation: Institute for Biomedical Sciences of Pain and Institute for Functional Brain Disorders, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.|Key Laboratory of Brain Stress and Behavior, People's Liberation Army, Xi'an, 710038, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Institute for Biomedical Sciences of Pain and Institute for Functional Brain Disorders, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.|Key Laboratory of Brain Stress and Behavior, People's Liberation Army, Xi'an, 710038, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.affiliation: Institute for Biomedical Sciences of Pain and Institute for Functional Brain Disorders, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China.
authors.forename: Yun-Fei
authors.initials: YF
authors.lastname: Lu
authors.affiliation: School of Stomatology, The Fourth Military Medical University, Xi'an, 710032, China. jchsmg@fmmu.edu.cn.
authors.forename: Su-Min
authors.initials: SM
authors.lastname: Guan
authors.affiliation: Institute for Biomedical Sciences of Pain and Institute for Functional Brain Disorders, Tangdu Hospital, The Fourth Military Medical University, Xi'an, 710038, China. junchen@fmmu.edu.cn.|Key Laboratory of Brain Stress and Behavior, People's Liberation Army, Xi'an, 710038, China. junchen@fmmu.edu.cn.|Beijing Institute for Brain Disorders, Beijing, 100069, China. junchen@fmmu.edu.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004195:Disease Models, Animal; D000431:Ethanol / Q000494:pharmacology*; D018756:GABA Antagonists / Q000494:pharmacology; D058785:GABA-A Receptor Agonists / Q000494:pharmacology; D006930:Hyperalgesia / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D008845:Microinjections; D009118:Muscimol / Q000494:pharmacology; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018079:Receptors, GABA / Q000378:metabolism*; D018709:Statistics, Nonparametric
chemical_list: D002492:Central Nervous System Depressants; D018756:GABA Antagonists; D058785:GABA-A Receptor Agonists; D018079:Receptors, GABA; D009118:Muscimol; D000431:Ethanol; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D010751:Phosphopyruvate Hydratase; D001640:Bicuculline
keywords: Empathy; Ethanol; GABAA receptor; Pain perception; mPFC