Segerdahl M, Karelov A
Center for Surgical Sciences, Unit for Anesthesia, Karolinska Institutet at Huddinge University Hospital, Stockholm, Sweden.
Acta Physiol Scand. 2004 Mar;180(3):301-6. doi: 10.1046/j.0001-6772.2003.01239.x.
Endogenous adenosine is considered a prominent pain mediator in ischaemia. In contrast, it has been shown that exogenous adenosine can reduce tourniquet induced ischaemic pain in healthy volunteers. The aim of this study was to investigate if pharmacological antagonism of endogenous adenosine actions with an intravenous infusion of theophylline could attenuate experimentally induced ischaemic pain.
Nineteen healthy volunteers, 11 males, eight female, received theophylline 7 mg kg-1 or placebo intravenously, in a randomized, double blind and crossover fashion, prior to a sub-maximum effort forearm tourniquet test. Experiments were carried out with 1-week intervals to avoid pre-conditioning. Pain scores [visual analogue scale (VAS), 0-100] were assessed every minute up to a maximum of 30 min.
The sum of pain scores (accumulation of VAS scores) was attenuated by theophylline, 691 [200-1550 (median and 25-75% percentiles)], compared with placebo, 1231 (545-1675), P < 0.001. Also, peak VAS pain was lower during theophylline treatment, 48 +/- 38 (mean +/- SD), compared with placebo, 74 +/- 27, P < 0.001. Blood pressure increased during the experiment with no difference between treatments. Heart rate was not affected by tourniquet or drug treatment.
It is concluded that the adenosine receptor antagonist theophylline is able to attenuate the development of ischaemia pain during experimental ischaemia in humans. This implies a role for adenosine as both facilitatory mediator and a modulator of ischaemia skeletal muscle pain.
内源性腺苷被认为是缺血过程中一种重要的疼痛介质。相比之下，已有研究表明外源性腺苷可减轻健康志愿者中止血带诱导的缺血性疼痛。本研究的目的是调查静脉输注氨茶碱对内源性腺苷作用进行药理学拮抗是否能减轻实验性诱导的缺血性疼痛。
19名健康志愿者，11名男性，8名女性，在进行次最大强度的前臂止血带试验前，以随机、双盲和交叉方式静脉接受7mg/kg氨茶碱或安慰剂。实验间隔1周进行以避免预处理。在长达30分钟的时间内每分钟评估疼痛评分[视觉模拟量表（VAS），0 - 100]。
与安慰剂组的1231（545 - 1675）相比，氨茶碱组的疼痛评分总和（VAS评分累积值）降低，为691[200 - 1550（中位数和25 - 75%百分位数）]，P < 0.001。此外，氨茶碱治疗期间的VAS疼痛峰值较低，为48 ± 38（平均值 ± 标准差），而安慰剂组为74 ± 27，P < 0.001。实验期间血压升高，各治疗组之间无差异。心率不受止血带或药物治疗的影响。
得出结论，腺苷受体拮抗剂氨茶碱能够减轻人体实验性缺血过程中缺血性疼痛的发展。这意味着腺苷在缺血性骨骼肌疼痛中既是促进性介质又是调节因子。
