Topical capsaicin-induced allodynia in unanesthetized primates: Pharmacological modulation
Topical capsaicin-induced allodynia in unanesthetized primates: Pharmacological modulation
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DOI：
10.1124/jpet.103.052381
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发表时间：
2003-09-01
影响因子：
3.5
通讯作者：
Kreek, MJ
中科院分区：
文献类型：
--
作者：
Butelman, ER;Ball, JW;Kreek, MJ
局部施用辣椒素产生热异常性痛，这种效果已被用于研究疼痛传导及其药理调节。本研究研究了外用辣椒素诱导的非麻醉恒河猴热异常性疼痛的参数及其中枢作用化合物[kappa-阿片激动剂：(5alpha, 7alpha, 8alpha)-(+)- n-甲基- n-(7-[1-吡啶基]-1-oxaspiro [4.5]dec-8-yl)-苯乙酰胺（U69,593）；非竞争性n -甲基- d -天冬氨酸（NMDA）拮抗剂：氯胺酮和MK-801（二唑西平）]。研究人员对恒河猴（n=4）进行温水脱尾实验（最长潜伏期为20秒），使用通常无害的热刺激（38度和42度）。将0.0013和0.004 M辣椒素溶液在1 cm(2)的斑块上局部施用于尾部；下半场联系)。局部辣椒素在两种温度下产生浓度依赖的热异常性疼痛，在局部辣椒素去除后15至90分钟被强烈检测到。局部给药“内源性香草素”n -花生四烯酰基多巴胺也观察到类似的异动性。卡帕激动剂U69,593 （0.01-0.1 mg/kg, s.c）剂量依赖性地阻止了辣椒素（0.004 M）在38度和42度诱导的异位性疼痛，并且在该模型中最大剂量U69,593也逆转了持续的异位性疼痛。两种NMDA拮抗剂，氯胺酮和MK-801（分别为0.32-1.8 mg/kg和0.032-0.056 mg/kg），在38°c时也能预防辣椒素引起的异位性疼痛，但在42°c时，剂量不同，不会产生强烈的热抗痛觉作用。在研究的最大剂量下，氯胺酮而不是MK-801也能短暂逆转正在进行的辣椒素诱导的异常性疼痛。目前的局部辣椒素给药模型可用于研究阿片类和非阿片类化合物在未麻醉的非人灵长类动物中在没有组织破坏的情况下的抗异痛觉作用，以及它们预防和逆转异痛觉的能力。
Topically administered capsaicin produces thermal allodynia, and this effect has been used to investigate pain transduction and its pharmacological modulation. This study investigated the parameters of topical capsaicin-induced thermal allodynia in unanesthetized rhesus monkeys and its pharmacological modulation by centrally acting compounds [a kappa-opioid agonist: (5alpha, 7alpha, 8alpha)-(+)-N-methyl-N-(7-[1-pyrrolidinyl]-1-oxaspiro [4.5]dec-8-yl)-benzeneacetamide (U69,593); and noncompetitive N-methyl-D-aspartate (NMDA) antagonists: ketamine and MK-801 (dizocilpine)]. Rhesus monkeys (n=4) were studied within the warm water tail withdrawal assay (20-s maximum latency), using thermal stimuli that are normally not noxious (38 and 42degreesC). Capsaicin was applied topically on the tail (0.0013 and 0.004 M capsaicin solution on a 1-cm(2) patch; 15-min contact). Topical capsaicin produced concentration-dependent thermal allodynia in both temperatures, robustly detected 15 to 90 min after topical capsaicin removal. A similar allodynic profile was observed with topical administration of the "endovanilloid" N-arachidonoyl-dopamine. The kappa-agonist U69,593 (0.01-0.1 mg/kg, s.c.) dose dependently prevented capsaicin (0.004 M)-induced allodynia in 38 and 42degreesC, and the largest U69,593 dose also reversed ongoing allodynia within this model. Two NMDA antagonists, ketamine and MK-801 (0.32-1.8 and 0.032-0.056 mg/kg, respectively), also prevented capsaicin-induced allodynia in 38degreesC, but only variably in 42degreesC, at doses that did not cause robust thermal antinociceptive effects. At the largest doses studied, ketamine but not MK-801 also briefly reversed ongoing capsaicin-induced allodynia. The present model of topical capsaicin administration may be used to study antiallodynic effects of opioid and nonopioid compounds, as well as their ability to prevent and reverse allodynia, in unanesthetized nonhuman primates in the absence of tissue disruption.