Neurobiology of Pain Laboratory, Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados (Cinvestav), Sede Sur. Calzada de los Tenorios 235, Col. Granjas Coapa, 14330 México, D.F., Mexico.
Centro de Investigación, División Académica de Ciencias de la Salud, Universidad Juárez Autónoma de Tabasco, 86150 Villahermosa, Tabasco, Mexico.
Eur J Pharmacol. 2014 Jul 5;734:91-7. doi: 10.1016/j.ejphar.2014.03.051. Epub 2014 Apr 12.
The activation of GABAA receptor by γ-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 α5 subunit-containing GABAA receptors to the inflammatory pain is unknown. The purpose of this study was to investigate the possible pronociceptive role of peripheral α5 subunit-containing GABAA 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 (-10min) with exogenous GABA (0.003-0.03µg/paw) or common GABAA receptor agonists muscimol (0.003-0.03µg/paw), diazepam (0.017-0.056µg/paw) or phenobarbital (1-100µg/paw) significantly increased 0.5% formalin-induced nociceptive behavior. The pronociceptive effects of GABA (0.03µg/paw), muscimol (0.03µg/paw), diazepam (0.056µg/paw) and phenobarbital (100µg/paw) were prevented by either the GABAA receptor antagonist bicuculline (0.01-0.1µg/paw) or selective α5 subunit-containing GABAA receptor inverse agonist L-655,708 (0.017-0.17µg/paw). The α5 subunit-containing GABAA receptor protein was expressed in dorsal root ganglion (DRG) and dorsal spinal cord of naïve rats. The formalin injection did not modify α5 subunit-containing GABAA receptor expression. Overall, these results suggest that peripheral α5 subunit-containing GABAA receptors play a pronociceptive role in the rat formalin test.
γ-氨基丁酸（GABA）激活初级传入纤维中的 GABAA 受体可产生去极化。在正常情况下，这种去极化会导致神经递质释放减少。因此，这种去极化仍然是抑制性的。然而，先前的研究表明，在炎症性疼痛中，GABA 通过增加 GABA 诱导的去极化，将其信号从抑制转变为兴奋。外周含有 α5 亚单位的 GABAA 受体在炎症性疼痛中的贡献尚不清楚。本研究旨在探讨外周含有 α5 亚单位的 GABAA 受体在福尔马林试验中对伤害性感受的可能作用。向右侧后爪背侧注射福尔马林（0.5%）可引起大鼠畏缩行为。同侧局部外周预先处理（-10min）外源性 GABA（0.003-0.03μg/爪）或常见 GABAA 受体激动剂 muscimol（0.003-0.03μg/爪）、地西泮（0.017-0.056μg/爪）或苯巴比妥（1-100μg/爪）可显著增加 0.5%福尔马林诱导的伤害性行为。GABA（0.03μg/爪）、mucimol（0.03μg/爪）、地西泮（0.056μg/爪）和苯巴比妥（100μg/爪）的促伤害作用可被 GABAA 受体拮抗剂 bicuculline（0.01-0.1μg/爪）或选择性 α5 亚单位包含 GABAA 受体反向激动剂 L-655,708（0.017-0.17μg/爪）所阻断。α5 亚单位包含的 GABAA 受体蛋白在背根神经节（DRG）和未处理大鼠的背侧脊髓中表达。福尔马林注射未改变 α5 亚单位包含的 GABAA 受体表达。总的来说，这些结果表明，外周含有 α5 亚单位的 GABAA 受体在大鼠福尔马林试验中具有促伤害作用。
