Gabapentin completely neutralize activation of morphine in the rat hypothalamus

Objective:Opioids are commonly used for the treatment of post-operative complication and pain. However no single class of drug has been found to be effective in alleviate post-operative pain and complications with acceptable side effects. Antihyperalgesic effect of gabapentin does not involve opiate pathways, reduced the need for opioids in post-operative treatment, blocks and reverse the antinociceptive opioids tolerance. and also prevent opiate withdrawal symptoms. A growing body of evidence suggests the existance of a functional interaction between gabapentin -morphine system. However, the neuroanatomical sites an molecular mechanism of action of gabapentin- morphine interaction to prevent and reverse morphine side effects as well as enhancement of the analgesic effect of morphine is not clear. The hypothalamus is a brain structure control both natural rewards and drugs of abuse but the cellular and molecular basis of this role is unclear. Therefore, we examined the combined effects of gabapentin-morphine on acute morphine induced c-Fos expression in rat hypothalamus, Methods: Combined effect of gabapentin-morphine was examined by means of c-Fos immunohistochemistry.Detection of c-Fos protein was performed using the peroxidase-antiperoxidase detection protocol, Results: Our present study demonstrated that, intraperitoneal administration of gabapentin (150 mg/kg) in combination with morphine (5 mg/kg) significantly (p<0.01) attenuated the acute morphine induced c-Fos expression in rat hypothalamus. Moreover, this study provides first evidence that hypothalamus is a neuro-anatomical site of gabapentin-morphine interaction to neutralize morphine activation. Conclusions: Present results indicated that gabapentin can be used as a tool to study the underlying molecular mechanism of morphine abuse in postoperative pain.