Liu M, Max M B, Robinovitz E, Gracely R H, Bennett G J
Neurobiology and Anesthesiology Branch, National Institute of Dental, Research, National Institutes of Health, Bethesda, MD 20892, USA.
J Pain Symptom Manage. 1998 Jul;16(1):10-20. doi: 10.1016/s0885-3924(98)00026-8.
Intradermal and topical application of capsaicin have been used to study mechanisms of mechanical allodynia (MA) and pinprick hyperalgesia (PPH) and the efficacy of drugs in relieving these symptoms. However, it is associated with significant inter- and intra-subject variability. In order to improve the model's sensitivity, we examined several potential sources of variability of capsaicin-evoked MA and PPH in healthy volunteers, including skin temperature fluctuations, method (intradermal vs. topical) and site (volar forearm vs. foot dorsum) of administration. In study I, 12 subjects received, in a 6-session, randomized, crossover trial, 1) 250 micrograms of intradermal (ID) CAP to the volar forearm with skin temperature fixed at 36 degrees C (36 ID). 2) 250 micrograms ID CAP with varying skin temperature (VT ID), or 3) 250 microliters of l% CAP patch placed on the skin at 36 degrees C. The resulting MA and PPH areas observed with each method were measured. In study II, a 4-session, randomized crossover trial, 12 subjects were given 100 micrograms ID CAP in the volar forearm or foot dorsum and subsequent areas of MA and PPH recorded. In study I, 5/12 subjects had small MA areas (< or = 5 cm2) and one subject had small PPH areas in at least 4/6 sessions. The most consistent intra-subject responses were seen with the 36 ID method. Correlation coefficients for the two sessions using the same method of administration were: MA; 36 ID r = 0.83, VT ID = 0.19. Topical r = 0.81; PPH: 36 ID r = 0.93; VT ID r = 0.38, Topical r = 0.78. In study II, 4/12 subjects had little MA for both forearm and foot though all subjects developed PPH. However, greater intra-subject consistency (MA: foot: r = 0.84; arm: r = 0.49; PPH: r = 0.87; r = 0.39) and significantly larger areas of MA (15.8 +/- 4.2 vs 9.1 +/- 2.5, p < 0.05) were seen with the foot. (PPH: foot: 28.9 +/- 6.7; arm: 21.6 +/- 4.2, NS). Large variability exists among subjects receiving CAP, with some developing minimal MA. However, these subjects may be screened out prior to entry, increasing the sensitivity of the model, which may be further improved by clamping the skin temperature.
辣椒素的皮内注射和局部应用已被用于研究机械性异常性疼痛（MA）和针刺样痛觉过敏（PPH）的机制以及药物缓解这些症状的疗效。然而，它存在显著的个体间和个体内变异性。为了提高该模型的敏感性，我们在健康志愿者中研究了辣椒素诱发的MA和PPH变异性的几个潜在来源，包括皮肤温度波动、给药方法（皮内注射与局部应用）和部位（掌侧前臂与足背）。在研究I中，12名受试者参加了一项为期6个阶段的随机交叉试验，1）将250微克皮内（ID）辣椒素注射到掌侧前臂，皮肤温度固定在36摄氏度（36 ID）。2） 250微克ID辣椒素，皮肤温度可变（VT ID），或3）将250微升1%辣椒素贴片贴于36摄氏度的皮肤上。测量每种方法所观察到的MA和PPH面积。在研究II中，一项为期4个阶段的随机交叉试验，12名受试者在掌侧前臂或足背接受100微克ID辣椒素，并记录随后的MA和PPH面积。在研究I中，5/12的受试者在至少4/6个阶段有小的MA面积（≤5平方厘米），一名受试者有小的PPH面积。36 ID方法观察到的个体内反应最一致。使用相同给药方法的两个阶段的相关系数为：MA；36 ID r = 0.83，VT ID = 0.19。局部应用r = 0.81；PPH：36 ID r = 0.93；VT ID r = 0.38，局部应用r = 0.78。在研究II中，4/12的受试者前臂和足部的MA都很少，尽管所有受试者都出现了PPH。然而，足部观察到更大的个体内一致性（MA：足部：r = 0.84；手臂：r = 0.49；PPH：r = 0.87；r = 0.39）和显著更大的MA面积（15.8±4.2对9.1±2.5，p < 0.05）。（PPH：足部：28.9±6.7；手臂：21.6±4.2，无显著性差异）。接受辣椒素的受试者之间存在很大变异性，一些受试者的MA最小。然而，这些受试者在入组前可被筛选出来，提高模型的敏感性，通过钳制皮肤温度可能会进一步改善。
