From the Departments of Neurosurgery (A.H.K., M.R.) and Anesthesiology and Critical Care Medicine (S.R.), Johns Hopkins University School of Medicine, Baltimore, Maryland; and Department of Pharmacology, Physiology, Neuroscience, School of Medicine, University of South Carolina, Columbia, South Carolina (H.K.M., R.A., B.P., S.P.W., S.S.). Current positions: Department of Pharmacy Practice and Pharmaceutical Sciences, University of Minnesota College of Pharmacy, Duluth, Minnesota (A.H.K.); and College of Health and Human Services, Concordia University, Portland, Oregon (S.S.).
Anesthesiology. 2018 May;128(5):967-983. doi: 10.1097/ALN.0000000000002063.
The current study used recombinant herpes simplex virus type I to increase expression of µ-opiate receptors and the opioid ligand preproenkephalin in peripheral nerve fibers in a mouse model of neuropathic pain. It was predicted that viral vector delivery of a combination of genes encoding the µ-opioid receptor and preproenkephalin would attenuate neuropathic pain and enhance opioid analgesia. The behavioral effects would be paralleled by changes in response properties of primary afferent neurons.
Recombinant herpes simplex virus type 1 containing cDNA sequences of the µ-opioid receptor, human preproenkephalin, a combination, or Escherichia coli lacZ gene marker (as a control) was used to investigate the role of peripheral opioids in neuropathic pain behaviors.
Inoculation with the µ-opioid receptor viral vector (n = 13) reversed mechanical allodynia and thermal hyperalgesia and produced leftward shifts in loperamide (ED50 = 0.6 ± 0.2 mg/kg vs. ED50 = 0.9 ± 0.2 mg/kg for control group, n = 8, means ± SD) and morphine dose-response curves (ED50 = 0.3 ± 0.5 mg/kg vs. ED50 = 1.1 ± 0.1 mg/kg for control group). In µ-opioid receptor viral vector inoculated C-fibers, heat-evoked responses (n = 12) and ongoing spontaneous activity (n = 18) were decreased after morphine application. Inoculation with both µ-opioid receptor and preproenkephalin viral vectors did not alter mechanical and thermal responses.
Increasing primary afferent expression of opioid receptors can decrease neuropathic pain-associated behaviors and increase systemic opioid analgesia through inhibition of peripheral afferent fiber activity.
本研究利用重组单纯疱疹病毒 I 型增加了外周神经纤维中μ-阿片受体和前脑啡肽原的表达，构建了一种神经性疼痛的小鼠模型。研究预测，同时表达μ-阿片受体和前脑啡肽原的基因的病毒载体传递，将减轻神经性疼痛并增强阿片类药物的镇痛作用。主要传入神经元反应特性的变化将与行为效应平行。
使用含有μ-阿片受体、人前脑啡肽原、组合或大肠杆菌 lacZ 基因标记（作为对照）的 cDNA 序列的重组单纯疱疹病毒 I 型，来研究外周阿片类物质在神经性疼痛行为中的作用。
μ-阿片受体病毒载体接种（n = 13）逆转了机械性痛觉过敏和热痛觉过敏，并使洛哌丁胺（ED50 = 0.6 ± 0.2 mg/kg 与对照组 ED50 = 0.9 ± 0.2 mg/kg，n = 8，平均值 ± SD）和吗啡剂量-反应曲线（ED50 = 0.3 ± 0.5 mg/kg 与对照组 ED50 = 1.1 ± 0.1 mg/kg）向左移位。在 μ-阿片受体病毒载体接种的 C 纤维中，热诱发反应（n = 12）和持续自发性活动（n = 18）在给予吗啡后减少。同时接种μ-阿片受体和前脑啡肽原病毒载体不会改变机械和热反应。
增加初级传入纤维中阿片受体的表达，可以通过抑制外周传入纤维的活动，减少与神经性疼痛相关的行为，并增强全身性阿片类药物的镇痛作用。
