μ opioid receptors and analgesia at the site of a peripheral nerve injury
μ opioid receptors and analgesia at the site of a peripheral nerve injury
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DOI：
10.1002/ana.10465
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发表时间：
2003-03-01
影响因子：
11.2
通讯作者：
Zochodne, DW
中科院分区：
文献类型：
--
作者：
Truong, W;Cheng, C;Zochodne, DW
阿片配体可能通过外周传入轴突上表达的受体发挥抗伤害作用。局部阿片受体是否可以减轻神经病理性疼痛尚不确定。在这项工作中，我们研究了与慢性压迫性损伤（CCI）大鼠坐骨神经病理性疼痛模型相关的局部μ阿片受体（MORs）的功能和表达。将低剂量吗啡或其载体持续灌注在CCI部位，注射器对注射物的身份不知情。吗啡，但不是它的载体，而不是等摩尔全身剂量的吗啡逆转热痛觉过敏的剂量相关，纳洛酮敏感的方式。此外，镇痛被赋予CCI后48小时和14天，时间与非常不同的神经修复阶段。等摩尔局部DAGO（[D-Ala 2，N-Me-Phe 4，Gly 5-（ol）]脑啡肽），一种选择性莫尔配体，提供类似的镇痛作用。局部吗啡也可减轻机械性痛觉超敏。莫尔蛋白表达于损伤部位近端的Cajal轴突终球、CCI损伤部位周围神经外膜鞘中异常再生的小轴突和CCI损伤远端残留的小轴突。CCI同侧感觉神经元表达莫尔的神经元比例增加。我们认为，局部莫尔表达的轴突可能被利用来调节某些形式的神经病理性疼痛。
Opioid ligands may exert antinociception through receptors expressed on peripheral afferent axons. Whether local opioid receptors might attenuate neuropathic pain is uncertain. In this work, we examined the function and expression of local mu opioid receptors (MORs) associated with the chronic constriction injury (CCI) model of sciatic neuropathic pain in rats. Low-dose morphine or its carrier were percutaneously superfused over the CCI site with the injector blinded to the identity of the injectate. Morphine, but not its carrier, and not equimolar systemic doses of morphine reversed thermal hyperalgesia in a dose-related, naloxone-sensitive fashion. Moreover, analgesia was conferred at both 48 hours and 14 days after CCI, times associated with very different stages of nerve repair. Equimolar local DAGO ([D-Ala2, N-Me-Phe4, Gly5-(ol)] enkephalin), a selective MOR ligand, provided similar analgesia. Local morphine also attenuated mechanical allodynia. MOR protein was expressed in axonal endbulbs of Cajal just proximal to the injury site, in aberrantly regenerating small axons in the epineurial sheath around the CCI site and in residual small axons distal to the CCI lesion. Sensory neurons ipsilateral to CCI had an increase in the proportion of neurons expressing MOR. We suggest that local MOR expressed in axons may be exploited to modulate some forms of neuropathic pain.