Vinegar R, Truax J F, Selph J L, Johnston P R
Division of Pharmacology, Wellcome Research Laboratories, Research Triangle Park, North Carolina 27709.
J Pharmacol Methods. 1990 Mar;23(1):51-61. doi: 10.1016/0160-5402(90)90008-9.
Subplantar injection of 250 micrograms of trypsin in the rat resulted in a biphasic increase in pain sensitivity (hyperalgesia) with peaks at 10 and 150 min separated by a period of decreased sensitivity to pain (hypoalgesia). Hyperalgesia was assessed by a decrease in response latency to a 3.0-kg force applied to the injected hind limb. Response latencies at 150 min were increased in a dose-dependent manner by pretreatment at 90 min with acetaminophen; phenacetin; the arachidonate cyclooxygenase inhibitors aspirin, indomethacin, and ibuprofen; and the opiate analgesics codeine and morphine. ED50s of 17, 13, 10, 0.48, 1.6, 3.9 and 1.2 mg/kg p.o. were obtained for these drugs, respectively. The hyperalgesia present at 150 min was not affected by pretreatment with antiinflammatory steroids, an antihistaminic, an antiserotonin agent, and an anticholinergic. We recommend measurement of drug-induced increase in response latencies produced 150 min after injection of 250 micrograms of trypsin as the basis for a new sensitive and selective analgesic assay. ED50s obtained in this assay correlate well with doses that are used clinically to produce analgesia. Development of the hypoalgesic component was selectively inhibited by pretreatment with an antiserotonin agent. Additional drug studies indicated that the algesic response to the subplantar injection of trypsin is the resultant of independent, temporally overlapping hyperalgesic and hypoalgesic components.
在大鼠足底注射250微克胰蛋白酶会导致疼痛敏感性（痛觉过敏）呈双相增加，在10分钟和150分钟时达到峰值，中间间隔一段疼痛敏感性降低（痛觉减退）的时期。通过对注射后肢施加3.0千克力时反应潜伏期的缩短来评估痛觉过敏。在90分钟时用对乙酰氨基酚、非那西丁、花生四烯酸环氧化酶抑制剂阿司匹林、吲哚美辛和布洛芬以及阿片类镇痛药可待因和吗啡进行预处理，150分钟时的反应潜伏期会以剂量依赖的方式增加。这些药物经口服给药的半数有效剂量（ED50）分别为17、13、10、0.48、1.6、3.9和1.2毫克/千克。150分钟时出现的痛觉过敏不受抗炎类固醇、抗组胺药、抗血清素剂和抗胆碱能药预处理的影响。我们建议将注射250微克胰蛋白酶150分钟后药物诱导的反应潜伏期增加的测量作为一种新的灵敏且选择性的镇痛测定方法的基础。该测定中获得的ED50与临床上用于产生镇痛作用的剂量密切相关。抗血清素剂预处理可选择性抑制痛觉减退成分的发展。其他药物研究表明，对足底注射胰蛋白酶的痛觉反应是独立的、时间上重叠的痛觉过敏和痛觉减退成分共同作用的结果。
