Ethanol Increases Mechanical Pain Sensitivity in Rats via Activation of GABA_A Receptors in Medial Prefrontal Cortex

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• 作者：Kai-Wen Geng ; Ting He ; Rui-Rui Wang ; Chun-Li Li ; Wen-Jun Luo…
• 关键词：Ethanol ; mPFC ; Pain perception ; GABAA receptor ; Empathy
• 刊名：Neuroscience Bulletin
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：32
• 期：5
• 页码：433-444
• 全文大小：3,496 KB
• 刊物主题：Neurosciences; Human Physiology; Anesthesiology; Anatomy; Neurology; Pain Medicine;
• 出版者：Springer Berlin Heidelberg
• ISSN：1995-8218
• 卷排序：32

文摘

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 (GABA_A) receptors are involved in mediating the ethanol effects, muscimol, a selective GABA_A receptor agonist, or bicuculline, a selective GABA_A 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 GABA_A receptors in the mPFC of rats.