Effect of acute caffeine administration on hyperalgesia and allodynia in a rat neuropathic pain model

Introduction: Damage to the central and peripheral nervous system causes neuropathic pain. Caffeine is a plant alkaloid and non-selective antagonist of A1, A2a and A2b adenosine receptors. It is reported that caffeine increases the threshold of pain. In this study, the effect of acute caffeine on behavioral responses of neuropathic pain was investigated. Materials and Methods: The present study was conducted on 56 adult male Wistar rats in the weight range of 220-250 g. Neuropathic pain was induced by chronic constriction injury (CCI(. Animals were randomly divided into 7 groups (n = 8): Control, Sham, CCI, CCI + Saline, and CCI + Caffeine (10, 50 and 100 mg/kg). Thermal hyperalgesia, mechanical and thermal allodynia has been done on days 4 ,7, 14, 21, 28 after CCI. Results: Neuropathic rats desmostrated increased pain thresholds. Notably, caffeine at a dose of 10 mg/kg significantly increased the thermal allodynia., but at doses of 50 and 100 mg/kg, it significantly decreased the thermal hyperalgesia and mechanical allodynia. Conclusion: Our findings indicated that the effects of caffeine on pain responses are dose-dependent. Probably the inhibition of adenosine A1 receptors by caffeine increases pain responses, while the inhibition of A2a and A2b adenosine receptors is associated with protective effect of caffeine against pain responses.