Abstract
Diabetic neuropathic pain is a usual consequence of diabetes. In this study, the formalin-induced pain and the diabetic neuropathy models were used in mice to investigate if the cytidine, uridine, and gabapentin treatments either alone or in combination can reduce nephropathic pain or not. To achieve our goals, cytidine, uridine, and gabapentin, either alone or in combination were orally administered to mice at a dose of 100 mg/kg. The formalin test was used to examine pain-related behaviors throughout both the primary and secondary phases. Further, the potential pain-relieving efficacy of these therapies was assessed in a diabetic neuropathy model produced by streptozotocin injection. Oral administration of the combination (cytidine + uridine + gabapentin) reduces formalin-induced pain-associated behavior in the first and second phases more than in each treatment alone. In the diabetic neuropathy model, administering the cytidine + uridine + gabapentin combination significantly reversed the pain threshold detected. The combination of cytidine, uridine, and gabapentin decreased as well as the elevated spinal p-CREB levels caused by formalin, which was reversed by pre-treatment with naloxone, yohimbine, and methysergide. This study reveals that the cytidine, uridine, and gabapentin combination have strong synergistic pain-relieving properties in both formalin-induced pain and diabetic neuropathy models more than each treatment alone.