外周镇痛的机制及临床研究

外周感觉神经末梢存在阿片受体,炎症能使其密度和活性增加,但临床局部应用阿片类药物尚未能取得满意的效果,如何能使阿片类药物局部应用达到临床镇痛效果尚需进一步研究。不能通过血脑屏障的阿片类药物和阿片肽代谢酶抑制剂也仅限于动物实验,临床实验尚未进行。免疫细胞是内源性阿片肽的一个重要来源,在外周炎症疼痛控制中有重要的作用,这对于免疫抑制的状态如癌症、糖尿病、获得性免疫缺陷综合征疼痛的解释以及炎症性疾病治疗策略的设计都是非常重要的。Mrg是一类新近发现的、位于外周神经组织的阿片受体。N-甲酰-D天冬氨酸受体是一种离子型谷氨酸受体,广泛存在于外周躯体或内脏的痛觉传导通路上,外周N-甲酰-D天冬氨酸受体的活化或表达的改变与疼痛发生发展密切相关。总之,阿片类药物的外周镇痛作用,可避免全身阿片类药物应用产生的呼吸抑制、成瘾、耐受等中枢不良反应,又为阿片类药物的应用开辟了新途径,但仍有许多问题需进一步研究。

Mechanism and Clinical Research of the Peripheral Analgesia

The opiate receptors are presented on the peripheral nerve fibre. The activation and number of opiate receptors can be increased by inflammation. The local administration of opioids are not successful in clinical trial. The aim of the study is to investigate the clinical analgesia efficieney of opioids given in local tissue. The experiment on the opioids which do not cross the bload-brain barrier and the metabolism enzyme inhibition of opioid peptide has not been studied in clinical patients. Immune cell-derived opioid peptides play an important role in the peripheral inhibition of pain in inflammatory tissue, thus it is important to explain the pain mechanism of these diseases such as cancer,diabetics and AIDS,in addition to designing the treatment strategies of imflammation, Mrg is a new opioid receptor in peripheral nervous tissue. NMDA receptor is an ionotropie receptor for glutamate and widely distributed in the nervous system. The change of the activation and expression of peripheral NMDA receptor are related to the development of pain. In conclusion, the peripheral analgesia of opioids can avoid the central side effects of systemic opioid, such as inhibition of respiratory, addition and tolerance.