Yamamoto T, Yaksh T L
Department of Anesthesiology, University of California, La Jolla 92093-0818.
Anesthesiology. 1991 Nov;75(5):817-26. doi: 10.1097/00000542-199111000-00014.
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.
人们对周围神经不完全损伤后人类疼痛状态的潜在机制了解甚少。为了更好地理解这一现象，本研究评估了鞘内注射吗啡、U - 50488H（U - 50）、（D - Pen2，D - Pen5）-脑啡肽（DPDPE）、ST - 91、巴氯芬、蝇蕈醇和5'-N - 乙基羧酰胺 - 腺苷（NECA）对正常大鼠以及坐骨神经单侧松结扎致后爪单侧感觉过敏大鼠热诱发后爪退缩潜伏期的影响。在一侧神经结扎的动物中，术后7 - 11天，结扎侧后爪的潜伏期通常比未结扎侧后爪短2 - 4秒。在慢性植入鞘内导管的正常大鼠中，观察到后爪退缩潜伏期呈剂量依赖性增加；活性顺序为：巴氯芬、ST - 91、吗啡、蝇蕈醇、DPDPE远大于U50、NECA大于或等于0。在损伤动物未结扎（无感觉过敏）的后爪中，鞘内给药也导致后爪退缩潜伏期呈剂量依赖性增加；效力顺序为：NECA、巴氯芬、吗啡、ST - 91、蝇蕈醇、DPDPE大于U50大于或等于0。对于NECA和吗啡，无感觉过敏后爪的半数有效剂量（ED50）值显著更低。对于感觉过敏的后爪，剂量 - 反应曲线与同时在无感觉过敏后爪获得的曲线平行，但明显右移3 - 5倍，感觉过敏后爪的活性顺序为巴氯芬、吗啡、蝇蕈醇、DPDPE大于ST - 91、NECA、U50大于或等于0。这些数据表明：1）在正常动物中改变热传入处理的脊髓受体系统在损伤动物感觉过敏的后爪中同样活跃；2）出乎意料的是，尽管给药前反应潜伏期相似，但在损伤大鼠无感觉过敏后爪中调节反应的某些受体系统（吗啡和NECA）比未损伤大鼠中的活性更高。
