Antinociceptive Effect of Gabapentin in Visceral Pain is not Mediated by GABAA or Opioid Receptors

Abstract

Aims: There is evidence supporting the antinociceptive effect of gabapentin in visceral pain, however, the underlying mechanism(s) is not determined yet. So this study was performed to evaluate probable involvement of opioid and GABAergic receptors in the gabapentin effects on acetic acid-induced visceral pain in mice. Place and Duration of Study: Kerman Neuroscience Research Center, Kerman University of Medical Sciences, Kerman, Iran, between June 2012 and March 2013. Methodology: The acetic acid test was induced by intraperitoneal injection (i.p.) of acetic acid 0.6% (10ml/kg of body weight) in male mice. Writhing reflex was measured as the number of abdominal contractions in 45min. Animals received saline (as control) or gabapentin (1, 5, 10, 25, 50, 100 or 200mg/kg/ i.p.) 40min before acetic acid. The least effective dose of gabapentin (50mg/kg i.p.) was selected for further assessments and mice were pretreated either picrotoxin (0.75, 1 and 1.5mg/kg/i.p.) as chloride channel blocker, bicuculline (0.5, 0.75, 1.5 and 2mg/kg) as GABAA receptor antagonist or naloxone (2mg/kg/i.p.) as opioid receptor antagonist, 10min before gabapentin (50mg/kg i.p.) treatment. Separate groups received naloxone or picrotoxin (1.5mg/kg) or bicuculline (2mg/kg) alone 10min before saline in acetic acid induced visceral contractions test. Results: Gabapentin reduced acetic acid-induced writhing in dose-dependent manner. Visceral contractions following naloxone, picrotoxin and bicuculline administration prior to gabapentin was not significantly different from that of gabapentin alone. Only toxic doses of picrotoxin and bicuculline (1.5 and 2mg/kg, respectively) abolished the inhibitory effect of gabapentin. Conclusion: The effect of gabapentin on visceral nociception is not mediated through opioid and/or GABAA receptors.