Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore Neurobiology Programme, Life Sciences Institute, National University of Singapore, Singapore Defence Medical and Environmental Research Institute, DSO National Laboratories, Singapore.
Pain. 2011 Nov;152(11):2528-2542. doi: 10.1016/j.pain.2011.07.019. Epub 2011 Sep 8.
The medial septum is anatomically and functionally linked to the hippocampus, a region implicated in nociception. However, the role of medial septum in nociception remains unclear. To investigate the role of the region in nociception in rats, muscimol, a GABA agonist, or zolpidem, a positive allosteric modulator of GABA(A) receptors, was microinjected into medial septum to attenuate the activity of neurons in the region. Electrophysiological studies in anesthetized rats indicated that muscimol evoked a stronger and longer-lasting suppression of medial septal-mediated activation of hippocampal theta field activity than zolpidem. Similarly, microinjection of muscimol (1 or 2 μg/0.5 μl) into the medial septum of awake rats suppressed both licking and flinching behaviors in the formalin test of inflammatory pain, whereas only the latter behavior was affected by zolpidem (8 or 12 μg/0.5 μl) administered into the medial septum. Interestingly, both drugs selectively attenuated nociceptive behaviors in the second phase of the formalin test that are partly driven by central plasticity. Indeed, muscimol reduced the second phase behaviors by 30% to 60%, which was comparable to the reduction seen with systemic administration of a moderate dose of the analgesic morphine. The reduction was accompanied by a decrease in formalin-induced expression of spinal c-Fos protein that serves as an index of spinal nociceptive processing. The drug effects on nociceptive behaviors were without overt sedation and were distinct from the effects observed after septal lateral microinjections. Taken together, these findings suggest that the activation of medial septum is pro-nociceptive and facilitates aspects of central neural processing underlying nociception.
中隔区在解剖学和功能上与海马体相连，海马体是一个与伤害感受有关的区域。然而，中隔区在伤害感受中的作用尚不清楚。为了研究该区域在大鼠伤害感受中的作用，将 GABA 激动剂 muscimol 或 GABA(A) 受体正变构调节剂唑吡坦微注射到中隔区以抑制该区域神经元的活性。麻醉大鼠的电生理研究表明，muscimol 诱发的中隔介导的海马场 theta 活动激活的抑制作用比唑吡坦更强且持续时间更长。同样，将 muscimol（1 或 2 μg/0.5 μl）微注射到清醒大鼠的中隔区，可抑制福尔马林致炎痛试验中的舔舐和退缩行为，而唑吡坦（8 或 12 μg/0.5 μl）仅影响后者行为中隔区给药。有趣的是，这两种药物选择性地减轻了福尔马林试验第二阶段的伤害感受行为，而第二阶段的行为部分是由中枢可塑性驱动的。事实上，muscimol 将第二阶段的行为减少了 30%至 60%，与系统给予中等剂量阿片类镇痛药吗啡所观察到的减少量相当。这种减少伴随着福尔马林诱导的脊髓 c-Fos 蛋白表达的减少，c-Fos 蛋白作为脊髓伤害感受处理的指标。药物对伤害感受行为的影响没有明显的镇静作用，并且与中隔侧部微注射后观察到的影响不同。总之，这些发现表明中隔区的激活是伤害感受的促进因素，并促进了伤害感受的中枢神经处理。
