Drummond P D, Lipnicki D M
School of Psychology, Murdoch University, Western Australia.
Br J Clin Pharmacol. 2001 Sep;52(3):289-95. doi: 10.1046/j.0306-5251.2001.01445.x.
Noradrenaline increases thermal hyperalgesia in skin sensitized to heat by the topical application of capsaicin. The aim of this study was to determine whether desensitization to the hyperalgesic effects of noradrenaline would develop after repeated local administrations of noradrenaline in the skin of the forearm.
Noradrenaline and saline were administered to the forearm by iontophoresis (200 microA, 2 min, over a surface area of 3.1 cm(2)) two times per day for 4-10 days in 19 healthy subjects. The adequacy of the desensitization procedure was evaluated by measuring noradrenaline-induced vasoconstriction with laser Doppler fluxmetry. Thresholds and pain ratings to heat were then investigated at treated and control sites before and after the topical application of capsaicin, and after the iontophoresis of noradrenaline.
At previously untreated sites blood flow was 49 +/- 14% (+/- 95% confidence intervals) lower than flow at reference sites after the iontophoresis of noradrenaline. Vascular signs of adrenergic desensitization developed after 4-5 days of repeated local administration of noradrenaline in the majority of subjects. In those whose vessels constricted after the acute administration of noradrenaline, the adrenergic response averaged 23 +/- 15% at the desensitized site compared with 61 +/- 9% at previously untreated sites (P < 0.001). However, similar signs developed after repeated iontophoreses of saline (adrenergic response 7 +/- 16% compared with 58 +/- 15% at previously untreated sites, P < 0.001). Both the noradrenaline and saline treatments inhibited thermal hyperalgesia after the topical application of capsaicin. Heat-pain thresholds averaged 43.2 +/- 2.5 degrees C and 43.0 +/- 2.3 degrees C at the noradrenaline and saline pretreated sites compared with 41.4 +/- 2.7 degrees C at the control site (P < 0.05 and P < 0.06, respectively). On a 0-10 scale, heat-pain ratings to a 7 s, 45 degrees C stimulus averaged 3.8 +/- 1.6 and 3.5 +/- 1.7 at the noradrenaline and saline pretreated sites compared with 5.3 +/- 1.6 at the control site (P < 0.05). After the iontophoresis of noradrenaline heat-pain ratings increased 1.6 +/- 1.4 at the site pretreated with saline (P < 0.05) compared with only 0.4 +/- 1.0 at the site pretreated with noradrenaline (not significant), consistent with local adrenergic desensitization.
We conclude that repeated iontophoreses of noradrenaline or saline inhibit vasoconstriction to noradrenaline, and also inhibit increases in thermal hyperalgesia evoked by capsaicin. The release of endogenous stores of noradrenaline by iontophoretic currents might contribute to these effects.
去甲肾上腺素可增强经辣椒素局部涂抹致敏的皮肤对热的痛觉过敏。本研究旨在确定在前臂皮肤反复局部给予去甲肾上腺素后，是否会出现对去甲肾上腺素痛觉过敏作用的脱敏现象。
对19名健康受试者的前臂进行离子电渗疗法（200微安，2分钟，作用面积3.1平方厘米），每天两次给予去甲肾上腺素和生理盐水，持续4 - 10天。通过激光多普勒血流仪测量去甲肾上腺素诱导的血管收缩来评估脱敏程序是否充分。然后在局部涂抹辣椒素之前和之后，以及去甲肾上腺素离子电渗之后，分别在治疗部位和对照部位研究对热的阈值和疼痛评分。
在先前未治疗的部位，去甲肾上腺素离子电渗后血流量比参考部位低49±14%（±95%置信区间）。在大多数受试者中，反复局部给予去甲肾上腺素4 - 5天后出现了肾上腺素能脱敏的血管征象。在急性给予去甲肾上腺素后血管收缩的受试者中，脱敏部位的肾上腺素能反应平均为23±15%，而先前未治疗部位为61±9%（P < 0.001）。然而，在反复进行生理盐水离子电渗后也出现了类似的征象（肾上腺素能反应为7±16%，而先前未治疗部位为58±15%，P < 0.001）。去甲肾上腺素和生理盐水处理均在局部涂抹辣椒素后抑制了热痛觉过敏。在去甲肾上腺素和生理盐水预处理部位，热痛阈值平均分别为43.2±2.5℃和43.0±2.3℃，而对照部位为41.4±2.7℃（分别为P < 0.05和P < 0.06）。在0 - 10分的评分标准下，对于7秒、45℃的刺激，去甲肾上腺素和生理盐水预处理部位的热痛评分平均分别为3.8±1.6和3.5±1.7，而对照部位为5.3±1.6（P < 0.05）。去甲肾上腺素离子电渗后，生理盐水预处理部位的热痛评分增加了1.6±1.4（P < 0.05），而去甲肾上腺素预处理部位仅增加了0.4±1.0（无统计学意义），这与局部肾上腺素能脱敏一致。
我们得出结论，反复进行去甲肾上腺素或生理盐水离子电渗可抑制对去甲肾上腺素的血管收缩作用，也可抑制辣椒素诱发的热痛觉过敏增加。离子电流引起的内源性去甲肾上腺素释放可能导致了这些效应。
