Chronic pain has a debilitating consequences on health and lifestyle. The currently available
analgesics are often ineffective and accompanied by undesirable adverse effects. Although
adenosine receptors (AR) activation can affect nociceptive, inflammatory, and
neuropathic pain states, the specific regulatory functions of its subtypes (A1, A2A, A2B and A3 ARs) are not fully understood. The aim of this study was to investigate the role of different AR
ligands on inflammatory
pain. The von Frey filament test was used to assess the anti-nociceptive effects of
adenosine ligands on Complete
Freund's Adjuvant (CFA)-induced
mechanical allodynia in (180-220 g) adult male Sprague Dawley rats (expressed as paw withdrawal threshold, PWT). Neither the A2AAR selective agonist
CGS 21680 hydrochloride (0.1, 0.32 and 1 mg/kg) nor the A2BAR selective agonist
BAY 60-6583 (0.1, 0.32 and 1 mg/kg) produced any significant reversal of the PWT. However, the A1AR selective agonist ( ±)-5'-Chloro-5'-deoxy-ENBA, the A3AR selective agonist
2-Cl-IB-MECA, the A2AAR selective antagonist
ZM 241385 and the A2BAR selective antagonist PSB 603 produced a significant reversal of the PWT at the highest dose of 1 mg/kg. Co-administration of the selective antagonists of A1AR and A3AR PSB36 (1 mg/ml) and MRS-3777 (1 mg/ml); respectively, significantly reversed the anti-nociceptive effects of their corresponding agonists. Furthermore,
calcium imaging studies reveled that the effective AR
ligands in the behavioral assay also significantly inhibit
capsaicin-evoked
calcium responses in cultured rat dorsal root ganglia (DRG) neurons. In conclusion, modulating the activity of the transient receptor potential vanilloid 1 (
TRPV1) receptor by ARs
ligands could explain their anti-nociceptive effects observed in vivo. Therefore, the cross talk between ARs and
TRPV1 receptor may represent a promising targets for the treatment of inflammatory
pain conditions.