Bittencourt da Silva Larissa, Karshenas Ali, Bach Flemming Winther, Rasmussen Sten, Arendt-Nielsen Lars, Gazerani Parisa
Pain Res Manag. 2014 May-Jun;19(3):126-32. doi: 10.1155/2014/410415.
The analgesic action of botulinum neurotoxin type A (BoNTA) has been linked to the blockade of peripheral release of neuropeptides and neurotransmitters in animal models; however, there is no direct evidence of this in humans.
To investigate the effect of BoNTA on glutamate release in humans, using an experimental model of pain and sensitization provoked by capsaicin plus mild heat.
Twelve healthy volunteers (six men, six women) were pretreated with BoNTA (10 U) on the volar forearm and with a saline control on the contralateral side. Dermal microdialysis was applied one week later to collect interstitial samples before and after the application of a capsaicin patch (8%) plus mild heat (40°C⁄60 min) to provoke glutamate release, pain and vasodilation. Samples were collected every hour for 3 h using linear microdialysis probes (10 mm, 100 kD). Dialysate was analyzed for glutamate concentration. Pain intensity and skin vasomotor reactions (temperature and blood flow changes) were also recorded.
BoNTA significantly reduced glutamate release compared with saline (P<0.05). The provoked pain intensity was lower in the BoNTA-pretreated arm (P<0.01). The reduction in pain scores was not correlated with glutamate level. Cutaneous blood flow (P<0.05), but not cutaneous temperature (P≥0.05), was significantly reduced by BoNTA. There was a correlation between glutamate level and skin blood flow (r=0.58⁄P<0.05) but not skin temperature (P≥0.05). No differences according to sex were observed in any response.
The present study provided the first direct evidence supporting the inhibitory effect of BoNTA on glutamate release in human skin, which is potentially responsible for some of the analgesic action of BoNTA.
在动物模型中，A型肉毒杆菌神经毒素（BoNTA）的镇痛作用与神经肽和神经递质的外周释放受阻有关；然而，在人类中尚无直接证据证明这一点。
使用辣椒素加轻度热刺激引发疼痛和致敏的实验模型，研究BoNTA对人体谷氨酸释放的影响。
12名健康志愿者（6名男性，6名女性）在前臂掌侧接受BoNTA（10 U）预处理，对侧接受生理盐水对照。一周后进行皮肤微透析，在应用辣椒素贴片（8%）加轻度热刺激（40°C/60分钟）以引发谷氨酸释放、疼痛和血管舒张之前和之后收集组织间液样本。使用线性微透析探针（10 mm，100 kD）每小时收集样本，持续3小时。分析透析液中的谷氨酸浓度。还记录疼痛强度和皮肤血管舒缩反应（温度和血流变化）。
与生理盐水相比，BoNTA显著降低了谷氨酸释放（P<0.05）。BoNTA预处理的手臂引发的疼痛强度较低（P<0.01）。疼痛评分的降低与谷氨酸水平无关。BoNTA显著降低了皮肤血流量（P<0.05），但未降低皮肤温度（P≥0.05）。谷氨酸水平与皮肤血流量之间存在相关性（r=0.58/P<0.05），但与皮肤温度无关（P≥0.05）。在任何反应中均未观察到性别差异。
本研究提供了首个直接证据，支持BoNTA对人体皮肤中谷氨酸释放的抑制作用，这可能是BoNTA部分镇痛作用的原因。
