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在持续性内脏痛模型中,预先鞘内注射N-甲基-D-天冬氨酸(NMDA)受体拮抗剂(AP-5)可预防反射亢进。

Pre-emptive intrathecal administration of an NMDA receptor antagonist (AP-5) prevents hyper-reflexia in a model of persistent visceral pain.

作者信息

Rice Andrew S C, McMahon Stephen B

机构信息

Nuffield Department of Anaesthetics and Oxford Regional Pain Relief Unit, OxfordUK Sherrington School of Physiology, UMDS, London SE1 7EH UK.

出版信息

Pain. 1994 Jun;57(3):335-340. doi: 10.1016/0304-3959(94)90009-4.

DOI:10.1016/0304-3959(94)90009-4
PMID:7936711
Abstract

Dorsal horn sensitization following somatic noxious stimuli is partly mediated by the N-methyl-D-aspartate (NMDA) sub-type of glutamate receptor. This phenomenon has been comparatively sparsely investigated in the area of visceral pain. We have therefore investigated the role of spinal NMDA receptors in central sensitization in an animal model of persistent visceral pain. In anaesthetized rats the lumbosacral spinal cord was exposed by laminectomy and the pre-emptive effect of intrathecal AP-5 upon the hyper-reflexia associated with chemical inflammation of the bladder was investigated. The effect of intrathecal AP-5 (an NMDA receptor antagonist) upon the normal cystometrogram (CMG) was also measured. AP-5 (125-1000 micrograms) prevented the hyper-flexia associated with bladder inflammation in a dose-dependant fashion. In general, within the dose range 62.5-1000 micrograms, AP-5 had no significant effect upon the normal micturition reflex. However, at the top of this dose range a minor non-significant depression of this reflex was noted. NMDA receptors do not appear to mediate the micturition reflex at a spinal cord level. However, they are involved in the induction of hyper-reflexia following urinary bladder inflammation, this hyper-reflexia can be prevented by pre-emptive intrathecal administration of AP-5.

摘要

躯体伤害性刺激后背角敏化部分由谷氨酸受体的N-甲基-D-天冬氨酸(NMDA)亚型介导。这种现象在内脏痛领域的研究相对较少。因此,我们在持续性内脏痛动物模型中研究了脊髓NMDA受体在中枢敏化中的作用。在麻醉大鼠中,通过椎板切除术暴露腰骶脊髓,研究鞘内注射AP-5对膀胱化学性炎症相关的反射亢进的预防作用。还测量了鞘内注射AP-5(一种NMDA受体拮抗剂)对正常膀胱压力图(CMG)的影响。AP-5(125 - 1000微克)以剂量依赖性方式预防了与膀胱炎症相关的反射亢进。一般来说,在62.5 - 1000微克的剂量范围内,AP-5对正常排尿反射无显著影响。然而,在该剂量范围上限,观察到该反射有轻微的非显著性抑制。NMDA受体似乎在脊髓水平不介导排尿反射。然而,它们参与膀胱炎症后反射亢进的诱导,这种反射亢进可通过鞘内预先注射AP-5来预防。

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