Department of Physiology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
Exp Neurol. 2011 Mar;228(1):19-29. doi: 10.1016/j.expneurol.2010.12.004. Epub 2010 Dec 10.
Dopaminergic and glutamatergic inputs converge on nucleus accumbens (NAC) and affect the neuropathic pain. We tested the effects of daily systemic administration of dizocilpine (MK-801), a N-methyl-d-Aspartate (NMDA) noncompetitive receptor antagonist, or apomorphine (APO), a dopamine (DA) D1 and D2 receptor agonist, on neuropathic manifestations in the chronic constriction injury (CCI) and the spared nerve injury (SNI) models of mononeuropathy in rats. Six groups of rats were subjected to CCI or SNI neuropathy and 5-7 days later received daily intraperitoneal (ip) injections of saline, MK-801, or APO for two weeks. Tests for nociception and motor behaviors were performed at regular intervals. Tactile and cold allodynia were assessed using von Frey hairs or acetone drops, respectively. Heat hyperalgesia was assessed by the paw withdrawal test. Tests were performed before administering the daily injections. Another four groups of rats were subjected to SNI surgery, and then had their NAC (contralateral to the lesioned paw) perfused for two weeks with MK-801, saline, APO+ascorbic acid, or ascorbic acid alone using mini-osmotic pumps. Behavioral manifestations were assessed as above. Systemic daily injections of MK-801 and APO markedly attenuated the neuropathic manifestations in the CCI and SNI models with a minimal effect on cold allodynia. The same results were seen in the SNI model with chronic perfusion of NAC. Our results suggest that daily systemic administration of DA agonists and NMDA antagonists can attenuate neuropathic pain manifestations and that the NAC is involved in the modulation of neuropathic-like behaviors.
多巴胺能和谷氨酸能输入会聚于伏隔核（NAC）并影响神经病理性疼痛。我们测试了每日系统给予地卓西平（MK-801），一种 N-甲基-D-天冬氨酸（NMDA）非竞争性受体拮抗剂，或阿扑吗啡（APO），一种多巴胺（DA）D1 和 D2 受体激动剂，对大鼠单神经病变的慢性缩窄损伤（CCI）和 spared 神经损伤（SNI）模型中神经病理性表现的影响。六组大鼠接受 CCI 或 SNI 神经病，并在 5-7 天后接受每日腹腔内（ip）注射盐水、MK-801 或 APO 两周。定期进行疼痛和运动行为测试。使用 von Frey 毛发或丙酮滴分别评估触觉和冷觉过敏。热痛觉过敏通过足底撤回测试评估。测试在每日注射前进行。另外四组大鼠接受 SNI 手术，然后使用微型渗透泵将 NAC（与损伤足相对侧）持续灌注 MK-801、盐水、APO+抗坏血酸或抗坏血酸两周。如上所述评估行为表现。每日系统注射 MK-801 和 APO 明显减轻 CCI 和 SNI 模型中的神经病理性表现，对冷觉过敏的影响最小。在 NAC 慢性灌注的 SNI 模型中也观察到相同的结果。我们的结果表明，每日系统给予 DA 激动剂和 NMDA 拮抗剂可减轻神经病理性疼痛表现，并且 NAC 参与调节神经病理性样行为。
