Experimentally induced ischaemic pain in healthy humans is attenuated by the adenosine receptor antagonist theophylline.

Author(s): Segerdahl M, Karelov A

Affiliation(s): Center for Surgical Sciences, Unit for Anesthesia, Karolinska Institutet at Huddinge University Hospital, Stockholm, Sweden.

Publication date & source: 2004-03, Acta Physiol Scand., 180(3):301-6.

Publication type: Clinical Trial; Randomized Controlled Trial

AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.