Suppressive Effects of Intrathecal Application of Diazepam on Visceral Pain and Hyperalgesia Induced by Intracolonic Instillation of Formalin

Using an animal model of colonic inflammation, the effects of intrathecal (i.t.) diazepam (0.02 mg/kg, 0.08 mg/kg and 0.15 mg/kg) on visceral pain-related behaviors and hyperalgesia associated with colonic inflammation were investigated. In this visceral pain model, acute visceral pain response was induced by intracolonic (i.c.) injection of 0.5 ml of dilute formalin (2%, 5% and 10%) in rats, and the peak pain behavioral response and hyperalgesia were evoked by i.c. 5% formalin. I.t. diazepam (0.02 mg/kg, 0.08 mg/kg and 0.15 mg/kg) followed 10 min later by i.c. injection of 5% formalin, attenuated the visceral pain behaviors induced by 5% formalin in a dose dependent manner. Of the three doses tested, the duration of the suppressive effect of 0.15 mg/kg diazepam on visceral pain was the longest, which is 60 min compared with 45 min at other two doses. Moreover, i.t. pretreatment with 0.08 mg/kg diazepam attenuated the hyperalgesia induced by i.c. injection of 5% formalin. The findings in our studies shown that i.t. diazepam had a suppressive effect on visceral pain associated with noxious stimulation of colon, and provided evidence that diazepam may be used as an analgesic drug in the future.