EFFECTS OF ADENOSINE RECEPTOR LIGANDS ON THE NOCICEPTION AND STRESS-INDUCED ANTINOCICEPTION IN MICE

Introduction: It is well known that exposure to different stressors caused a sequence of biochemical, physiological and behavioural changes including analgesia which is realised by activating multiple endogenous pain inhibitory systems. Although the existing data reveal the important role of the adenosine modulatory system in the processing of nociceptive information, scarce data are available for its role in stress-induced changes in nociception. Materials and Methods: Male ICR mice – controls and exposed to acute (120 minutes) restraint stress (RS) were used; Acetic acid-induced nociception (writhing test); Adenosine A1 receptor agonist N6-R phenylisopropil-adenosine (R-PIA, 0.5 mg/kg, intraperitoneally, IP), nonselective adenosine receptor antagonist theophylline (acute 75mg/kg, IP and chronic 75 mg/kg/day/14 days, IP). Results: RS and R-PIA decreased the visceral nociception in mice. Acute and chronic treatment with theophylline did not influence the pain reactions neither in nonstressed nor in stressed animals. R-PIA administered before restraint stress fully reversed stress–induced antinociception. Single dose of theophylline antagonized the effects of R-PIA both in nonstressed and stressed animals. Chronic theophylline did not antagonize the antinociceptive effect of R-PIA, but abolished R-PIA induced reversion of SIA. Conclusion: Endogenous adenosine is not able to change the RS-induced visceral antinociception, as theophylline did not show any effects on the stress. However, adenosine A1 receptors are involved both in the antinociception in the healthy mice and RS-induced antinociception, perhaps by different mechanism.