Spinal pharmacology of thermal hyperesthesia induced by incomplete ligation of sciatic nerve. I. Opioid and nonopioid receptors.
Spinal pharmacology of thermal hyperesthesia induced by incomplete ligation of sciatic nerve. I. Opioid and nonopioid receptors.
复制标题
坐骨神经不完全结扎引起的热感觉过敏的脊柱药理学。
DOI：
10.1097/00000542-199111000-00014
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发表时间：
1991
期刊：
影响因子：
8.8
通讯作者：
Yaksh,TL
中科院分区：
文献类型：
--
作者：
Yamamoto,T;Yaksh,TL
人类周围神经不完全性损伤后疼痛状态的潜在机制尚不清楚。为了更好地了解这一现象，本研究评价了鞘内注射吗啡、U-50 488H(U-50)、(D-Pen2，D-Pen5)-脑啡肽(DPDPE)、ST-91、巴氯芬、蝇草酚和5‘-N-乙基甲酰胺-腺苷(NECA)对正常大鼠和单侧坐骨神经松绑致后爪感觉过敏大鼠热诱发后爪缩足潜伏期的影响。在一条神经结扎的动物中，结扎的爪子在术后7-11天的后爪潜伏期通常比未结扎的爪子少2-4个S。在慢性鞘内导管准备的正常大鼠，观察到剂量依赖性的缩足潜伏期延长；活动顺序为：巴氯芬、ST-91、吗啡、蝇草酚、DPDPE远大于U50，NECA大于或等于0。在非结扎(非麻醉)动物的爪部，鞘内给药组的缩足潜伏期也呈剂量依赖性延长，其作用顺序为：NECA、巴氯芬、吗啡、ST-91、麝香酚、DPDPE>U50大于或等于0。对于NECA和吗啡，非麻醉后爪的半数有效剂量(ED50)值显著降低。高感觉爪的剂量-反应曲线与非高感觉爪平行，但显著右移3-5倍，高感觉爪的活性顺序为巴氯芬、吗啡、蝇香酚、DPDPE大于ST-91、NECA、U50大于或等于0。这些数据表明：1)改变正常动物热传入处理的脊髓感受器系统在受损动物的多觉爪子中同样活跃；以及2)出人意料的是，尽管有相似的药物前反应潜伏期，调节受损大鼠(吗啡和NECA)非多觉爪子反应的某些受体系统显示出比未受损大鼠更大的活性。
Mechanisms underlying the pain state in humans that follows incomplete injury to peripheral nerve are little understood. To gain better understanding of this phenomenon, this study evaluated the effects on the thermally evoked hind-paw withdrawal latency produced by the intrathecal administration of morphine, U-50 488H (U-50),(D-Pen2, D-Pen5)-enkephalin (DPDPE), ST-91, baclofen, muscimol, and 5'-N-ethylcarboxamide-adenosine (NECA) in normal rats and in rats with a hind paw rendered unilaterally hyperesthetic by the unilateral application of loose ligatures to the sciatic nerve. In the animals with one ligated nerve, the hind-paw latency for the ligated paw was typically 2-4 s less than that for the nonligated paw, at 7-11 days postoperatively. In normal rats prepared with chronic intrathecal catheters, dose-dependent increases in paw withdrawal latency were observed; the order of activity was: baclofen, ST-91, morphine, muscimol, DPDPE much greater than U50, NECA greater than or equal to 0. In the nonligated (nonhyperesthetic) paw of the lesioned animals, intrathecal agents also resulted in a dose-dependent increase in the paw withdrawal latency; the order of potency was: NECA, baclofen, morphine, ST-91, muscimol, DPDPE greater than U50 greater than or equal to 0. For both NECA and morphine, the median effective dose (ED50) values were significantly less in the nonhyperesthetic hind paw. For the hyperesthetic paw, the dose-response curves were parallel to those obtained concurrently in the nonhyperesthetic paw but were shifted significantly to the right by a factor of 3-5, with the rank order of activity in the hyperesthetic paw being baclofen, morphine, muscimol, DPDPE greater than ST-91, NECA, U50 greater than or equal to 0. These data indicate that 1) spinal receptor systems that alter thermal afferent processing in the normal animal are similarly active in the hyperesthetic paw of the lesioned animal; and 2) unexpectedly, despite similar predrug response latencies, certain receptor systems regulating the response in the nonhyperesthetic paw of the lesioned rat (morphine and NECA) show greater activity than in the nonlesioned rat.