Pain models display differential sensitivity to Ca2+-permeable non-NMDA glutamate receptor antagonists
Pain models display differential sensitivity to Ca2+-permeable non-NMDA glutamate receptor antagonists
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DOI：
10.1097/00000542-200110000-00028
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发表时间：
2001-10-01
期刊：
影响因子：
8.8
通讯作者：
Doom, CM
中科院分区：
文献类型：
--
作者：
Sorkin, LS;Yaksh, TL;Doom, CM
背景：钙离子通透性的非N-甲基-D-天冬氨酸受体存在于脊髓背角，在伤害性信息传递过程中可能是谷氨酸能传递的靶点。这项研究描述了与阻断相关的止痛药概况。在这些脊髓受体中，已知的作用于这些受体的毒剂是蜘蛛毒素Joro毒素(IST)和黄曲霉毒素(Philanthooxin)。皮下注射福尔马林前10min、足底注射角叉菜胶后、脊神经结扎致痛觉过敏大鼠给予JST(5杯)。在注射福尔马林和测试热潜伏期之前，给予较低剂量的JST(0.25和1.0Imug)。用Hargreaves盒测量热潜伏期，用von Frey毛发测量机械阈值，用皱纹计数法测量福尔马林反应。两种药物均可阻断热损伤所致的机械性痛觉异常。角叉菜胶后1h给予JST(5ug)可阻断热痛敏和机械性痛觉超敏的诱导。在福尔马林实验中，JST(5杯)对脊神经结扎后的痛觉过敏和角叉菜胶后3h给药均无影响。在福尔马林和热刺激试验中，最低剂量(0.25mug JST)在60-120min的预处理时间内可引起轻度的痛觉减退。结论：鞘内钙离子渗透性非N-甲基-D-天冬氨酸拮抗剂的行为效应表明该脊髓受体在调节组织损伤和炎症所致的痛敏状态中起着重要作用，其作用不同于其他谷氨酸受体拮抗剂。
Background: Ca2+-permeable non-N-methyl-D-aspartate receptors are found In the spinal dorsal horn and represent a presumptive target for glutamatergic transmission in nociceptive processing. This study characterized the analgesic profile associated with the blockade. of these spinal receptors by intrathecally delivered agents known to act at these receptors, the spider venom Joro toxin (IST) and philanthotoxin.Methods: Philanthotoxin (0.5, 2.5, or 5 mug) or JST (5 mug) was given spinally before thermal injury to the paw. JST (5 mug) was also given 10 min before subcutaneous formalin injection, after intraplantar administration of carrageenan, and to rats that were allodynic due to tight ligation of spinal nerves. Lower doses of JST (0.25 and 1.0 I mug) were given before formalin injection and testing of thermal latencies. Thermal latencies were measured using a Hargreaves box, mechanical thresholds using von Frey hairs, and formalin response by means of counting flinches.Results. Both agents blocked thermal Injury-induced mechanical allodynia. JST (5 mug) given 1 h after carrageenan blocked induction of thermal hyperalgesia and mechanical allodynia. JST (5 mug) had no effect in the formalin test, on allodynia after spinal nerve ligation, or when given 3 h after carrageenan. The lowest dose (0.25 mug JST) at pretreatment intervals of 60-120 min resulted in modest hypoalgesia during phase I formalin and thermal testing.Conclusions: The behavioral effect of intrathecal Ca2+ -permeable non-N-methyl-D-aspartate antagonists indicates an important role for this spinal receptor in regulating hyperalgesic states induced by tissue injury and inflammation and reveals an action that is distinct from those observed with other glutamate receptor antagonists.