Evidence for the participation of peripheral 伪₅ subunit-containing GABA_A receptors in GABA_A agonists-induced nociception in rats

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• 作者：Mariana Bravo-Herná ; ndez^a ; ^{marianabh26@hotmail.com" class="auth_mail} ; Luis Alberto Feria-Morales^b ; ^{lichoferia@hotmail.com" class="auth_mail} ; Jorge Elí ; as Torres-Ló ; pez^b ; ^c ; ^{jetorreslopez@hotmail.com" class="auth_mail} ; Claudia Cervantes-Durá ; n^a ; ^{espparmex@hotmail.com" class="auth_mail} ; Rodolfo Delgado-Lezama^d ; ^{rdelgado57@gmail.com" class="auth_mail} ; Vinicio Granados-Soto^a ; ^{vinicio_granadossoto@hotmail.com" class="auth_mail} ; Hé ; ctor Isaac Rocha-Gonzá ; lez^e ; ^{hector.isaac@gmail.com" class="auth_mail}
• 关键词：Bicuculline (PubChem CID ; 10237) ; Diazepam (PubChem CID ; 3016) ; GABA (PubChem CID ; 119) ; L-655 ; 708 (PubChem CID ; 5311203) ; Muscimol (PubChem CID ; 4266) ; Phenobarbital (PubChem CID ; 4763)
• 刊名：European Journal of Pharmacology
• 出版年：5 July 2014
• 年：2014
• 卷：734
• 期：Complete
• 页码：91-97
• 全文大小：916 K

文摘

The activation of GABA_A receptor by 纬-amino butyric acid (GABA) in primary afferent fibers produces depolarization. In normal conditions this depolarization causes a reduction in the release of neurotransmitters. Therefore, this depolarization remains inhibitory. However, previous studies have suggested that in inflammatory pain, GABA shifts its signaling from inhibition to excitation by an increased GABA-induced depolarization. The contribution of peripheral 伪₅ subunit-containing GABA_A receptors to the inflammatory pain is unknown. The purpose of this study was to investigate the possible pronociceptive role of peripheral 伪₅ subunit-containing GABA_A receptors in the formalin test. Formalin (0.5%) injection into the dorsum of the right hind paw produced flinching behavior in rats. Ipsilateral local peripheral pre-treatment (−10 min) with exogenous GABA (0.003–0.03 µg/paw) or common GABA_A receptor agonists muscimol (0.003–0.03 µg/paw), diazepam (0.017–0.056 µg/paw) or phenobarbital (1–100 µg/paw) significantly increased 0.5% formalin-induced nociceptive behavior. The pronociceptive effects of GABA (0.03 µg/paw), muscimol (0.03 µg/paw), diazepam (0.056 µg/paw) and phenobarbital (100 µg/paw) were prevented by either the GABA_A receptor antagonist bicuculline (0.01-0.1 µg/paw) or selective 伪₅ subunit-containing GABA_A receptor inverse agonist L-655,708 (0.017-0.17 µg/paw). The 伪₅ subunit-containing GABA_A receptor protein was expressed in dorsal root ganglion (DRG) and dorsal spinal cord of naïve rats. The formalin injection did not modify 伪₅ subunit-containing GABA_A receptor expression. Overall, these results suggest that peripheral 伪₅ subunit-containing GABA_A receptors play a pronociceptive role in the rat formalin test.