Bareggi S R, Pirola R, De Benedittis G
Department of Pharmacology, University of Milan, Italy.
Eur J Clin Pharmacol. 1998 May;54(3):231-5. doi: 10.1007/s002280050451.
The aim of this investigation was to elucidate whether the analgesic effect was due to the local aspirin or to the systemic drug. This was done by comparing skin and plasma levels of acetylsalicylic acid (ASA) and salicylic acid (SA) after topically administered ASA/diethyl ether (ADE) mixture in acute herpetic neuralgia (AHN) and postherpetic neuralgia (PHN). The analgesia and the plasma and skin levels of ASA were also determined after oral administration of aspirin.
Nineteen patients, 11 (57.9%) with AHN and 8 (42.1 %) with PHN were given, on different days, a single 500-mg oral dose of ASA or a topical dose (750 mg) of (ADE) daubed onto the painful skin. The analgesic effect was assessed by means of a visual analogue scale (VAS). Overall pain relief was graded as: excellent, good, fair, or poor. AHN as well as PHN patients had severe pain at baseline (6.83 and 5.93). Levels of ASA and SA in plasma and in the stratum corneum after adhesive tape stripping of the treated area were determined by HPLC.
After ADE application, the analgesic effect was very rapid and VAS scores were lower than at baseline. Pain significantly decreased by 82.6% after topical and 15.4% after oral ASA. After ADE, 95% of the patients had excellent or good pain relief, but after oral administration 79% of the patients had a poor response. Pain relief was similar in the two subgroups after ADE. Skin concentrations of ASA, but not of SA, after ADE were about 80- to 100-fold those after oral administration. Levels of ASA and SA in plasma after oral administration were similar to those previously found, but after ADE were undetectable or very low. Patients with excellent pain relief showed a trend towards higher ASA skin concentrations.
The analgesic effect can be obtained only after topical administration, because by this route the skin levels of ASA are much higher than after oral administration. The mechanism is exclusively local; there are no active drugs in plasma after topical administration.
本研究旨在阐明镇痛效果是由于局部使用的阿司匹林还是全身用药所致。通过比较急性疱疹性神经痛(AHN)和疱疹后神经痛(PHN)患者局部应用阿司匹林/乙醚(ADE)混合物后皮肤和血浆中乙酰水杨酸(ASA)和水杨酸(SA)的水平来实现这一目的。口服阿司匹林后也测定了镇痛效果以及血浆和皮肤中ASA的水平。
19例患者,11例(57.9%)为AHN患者,8例(42.1%)为PHN患者,在不同日期分别给予单次口服500 mg ASA或局部给予(ADE)(750 mg)涂抹于疼痛皮肤处。通过视觉模拟评分法(VAS)评估镇痛效果。总体疼痛缓解程度分为:优、良、中、差。AHN和PHN患者基线时疼痛均较严重(分别为6.83和5.93)。通过高效液相色谱法测定治疗区域胶带剥离后血浆和角质层中ASA和SA的水平。
应用ADE后,镇痛效果起效非常迅速,VAS评分低于基线水平。局部应用ASA后疼痛显著降低82.6%,口服后降低15.4%。应用ADE后,95% 的患者疼痛缓解为优或良,但口服给药后79% 的患者反应较差。应用ADE后两个亚组的疼痛缓解情况相似。应用ADE后皮肤中ASA的浓度,但SA的浓度并非如此,约为口服给药后的80至100倍。口服给药后血浆中ASA和SA的水平与之前发现的相似,但应用ADE后无法检测到或非常低。疼痛缓解为优的患者ASA皮肤浓度有升高趋势。
仅局部给药后可获得镇痛效果,因为通过该途径皮肤中ASA的水平远高于口服给药后。其机制完全是局部性的;局部给药后血浆中无活性药物。