Khakpay Roghaieh, Azaddar Maryam, Khakpay Fatemeh, Hatami Nemati Homeira
Department of Animal Science, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.
Department of Biology, Faculty of Basics Sciences, Varamin Branch, Islamic Azad University, Pishva, Iran.
Basic Clin Neurosci. 2017 Jan;8(1):51-60. doi: 10.15412/J.BCN.03080107.
Beside its autonomic functions, the nucleus paragigantocellularis lateralis (LPGi) is involved in the descending pain modulation. 17β-Estradiol is a neuroactive steroid found in several brain areas such as LPGi. Intra-LPGi microinjection of 17β-estradiol can elicit the analgesic responses. 17β-Estradiol modulates nociception by binding to estrogenic receptors as well as allosteric interaction with other membrane-bound receptors like GABA receptors. This study aimed to examine the role of GABA receptors in the pain modulating effect of intra-LPGi injection of 17β-estradiol.
To study the antinociceptive effects of 17β-estradiol, cannulation into the LPGi nucleus of male Wistar rats was performed. About 500 nL of drug was administered 15 minutes prior to formalin injection (50 μL of 4%). Then, formalin-induced flexing and licking behaviors were recorded for 60 minutes. For evaluating the role of GABA receptors in the estradiol-induced pain modulation, 17β-estradiol was administered into the LPGi nucleus 15 minutes after the injection of 25 ng/μL bicuculline (the GABA receptor antagonist). Then, the formalin-induced responses were recorded.
The results of the current study showed that intra-LPGi injection of 17β-estradiol decreased the flexing duration in both phases of formalin test (P<0.001); but it only attenuated the second phase of licking behavior (P<0.001). 17β-estradiol attenuated the second phase of formalin test of both behaviors (P<0.001). Bicuculline prevented the antinociceptive effect of intra-LPGi 17β-estradiol in both first and second phases of formalin-induced responses (P<0.001).
According to the results of this study, the analgesic effect of intra-LPGi 17β-estradiol on the formalin-induced inflammatory pain might be mediated via GABA receptors.
除了其自主神经功能外，外侧巨细胞旁核（LPGi）还参与下行性疼痛调制。17β-雌二醇是一种在包括LPGi在内的多个脑区发现的神经活性类固醇。向LPGi内微量注射17β-雌二醇可引发镇痛反应。17β-雌二醇通过与雌激素受体结合以及与其他膜结合受体（如GABA受体）的变构相互作用来调节伤害感受。本研究旨在探讨GABA受体在向LPGi内注射17β-雌二醇的疼痛调制效应中的作用。
为研究17β-雌二醇的抗伤害感受作用，对雄性Wistar大鼠进行LPGi核插管。在注射福尔马林（50μL 4%）前15分钟给予约500 nL药物。然后，记录福尔马林诱导的屈曲和舔舐行为60分钟。为评估GABA受体在雌二醇诱导的疼痛调制中的作用，在注射25 ng/μL荷包牡丹碱（GABA受体拮抗剂）15分钟后，将17β-雌二醇注入LPGi核。然后，记录福尔马林诱导的反应。
本研究结果表明，向LPGi内注射17β-雌二醇可缩短福尔马林试验两个阶段的屈曲持续时间（P<0.001）；但仅减弱了第二阶段的舔舐行为（P<0.001）。17β-雌二醇减弱了两种行为福尔马林试验的第二阶段（P<0.001）。荷包牡丹碱在福尔马林诱导反应的第一和第二阶段均阻止了向LPGi内注射17β-雌二醇的抗伤害感受作用（P<0.001）。
根据本研究结果，向LPGi内注射17β-雌二醇对福尔马林诱导的炎性疼痛的镇痛作用可能是通过GABA受体介导的。
