Effect of chronic caffeine administration on hyperalgesia in a rat neuropathic pain model: role of nitric oxide pathway

Background and Aim : Damage to the central and peripheral nervous system causes neuropathic pain. Caffeine is a non-selective antagonist of A1and A2A adenosine receptors (ARs). Some doses of caffeine have a protective effect on pain. Meanwhile, nitric oxide (NO) is partly involved in the central effects of caffeine. Thus, the purpose of this study was to investigate the effect of chronic caffeine administration on the thermal hyperalgesia in neuropathic rats and levels of nitric oxide metabolites.Methods : Wistar male rats (220-250 g) were used in this study (n=8). Neuropathic pain was induced by chronic constriction injury (CCI) of sciatic nerve. Thermal hyperalgesia was measured using plantar test. Following sciatic nerve ligation, caffeine was administered orally (100 and 300 mg/Lit) for 28 days. The control group received tap water. Pain thresholds were recorded on days 4, 7, 14, 21, and 28. Nitric oxide metabolites (NOx) were measured with the Griess method in lumbar spinal cord tissue on day 28.Results : Neuropathic rats showed decreased pain thresholds in thermal hyperalgesia. Chronic caffeine at the doses of 100 and 300 mg/L in drinking water for 28 days significantly alleviated hyperalgesia (P<0.01),(P<0.001). NOx levels remained unchanged in neuropathic rats and after chronic caffeine administration.Conclusion : The results of this study indicate that chronic caffeine administration can alleviate the hyperalgesia in neuropathic rats. It seems that NO pathway is not involved in the central effect of caffeine in CCI model.

Keywords:

Neuropathic Pain , Caffeine , Nitric Oxide , Hyperalgesia