Majallah-i Dānishgāh-i ̒Ulūm-i Pizishkī-i Bābul (Dec 2007)
THE EFFECT OF GABAPENTIN ON ACETIC ACID INDUCED VISCERAL PAIN: INVOLVMENT OF MU OPIOID & GABAa RECEPTORS
Abstract
BACKGROUND AND OBJECTIVES: Gabapentin is an anticonvulsant drug which also possesses antinociceptive effect in wide spectrum kind of pain, like neuropathic pain. However its effectiveness on visceral pain is not elucidated yet. This study was performed to investigate the effect of gabapentin on acetic acid induced visceral pain in mice and also to evaluate probable involvement of Mu opioid and gabaergic receptors on the gabapentin antinociception.METHODS: In this experimental study, adult male mice weighing 30g were divided into thirteen subsequent groups. In control group, animals received normal saline 40 min before intraperitoneal (ip) injections of 0.6% acetic acid (4ml/kg) and then visceral contractions were measured for 90 min. The mice were given gabapentin (25, 50, 100, & 200 mg/kg/i.p.) and then the visceral contractions were measured in the same way as controls. Other groups were given either naloxone as mu opiod antagonist (4mg/kg/i.p.), or the antagonists of GABAA receptors, picrotoxin (0.75, 1; 1.5 mg/kg/i.p.) or bicuculline (0.5, 0.75, 1.5, & 2 mg/kg/i.p.) 10 min prior to the most effective dose of gabapentin. Thereafter visceral contractions were counted similar to control group.FINDINGS: Gabapentin markedly reduced acetic acid induced visceral pain in mice and dose of 50mg/kg of gabapentin was the most effective (p<0.01). Visceral contractions following naloxone administration (4mg/kg/i.p) 10 min prior to gabapentin was not significantly different from gabapentin group. However, picrotoxin and bicuculline antagonized the inhibitory effect of gabapentin on visceral contractions in a dose dependent manner, i.e. the dose of 1.5 mg/kg/ip of picrotoxin or more like as the dose of 2mg/kg/ip of bicuculline increased the mean number of visceral contractions in comparison with gabapentin group which received 50mg/kg/ip (p<0.05). CONCLUSION: The results showed that picrotoxin and bicuculline are able to antagonize the antinociceptive effect of gabapentin on actic acid induced visceral pain in dose dependent manner. It is implicated that the effect of gabapentin on visceral pain may be mediated partly through the GABAA receptors.
