Continuous fentanyl administration and spontaneous withdrawal decreases home cage wheel running in rats with and without hindpaw inflammation.

Fentanyl is a potent analgesic with a rapid onset and short half-life that make it a useful treatment for pain and a lethal drug of abuse. The present study used voluntary home cage wheel running to assess the effect of hindpaw inflammation, fentanyl administration, and spontaneous fentanyl withdrawal. Fentanyl (0.32 or 1.0 mg/kg/day) or placebo osmotic pumps were implanted subcutaneously and rats received an intraplantar injection of Complete Freund's Adjuvant (CFA) or saline. Rats with hindpaw inflammation caused by CFA administration were less active than rats injected with saline into the hindpaw. The antinociceptive effect of 0.32 mg/kg/day of fentanyl was evident as a recovery of wheel running in these rats. Administration of 1 mg/kg/day of fentanyl almost completely inhibited wheel running during the first day in rats with and without hindpaw inflammation. Wheel running increased each subsequent day until the pumps were surgically removed after day 3. Withdrawal from 0.32 or 1 mg/kg/day of fentanyl caused a decrease in wheel running that lasted 2 days in rats without hindpaw inflammation. In contrast, withdrawal was only evident following termination of 1 mg/kg/day of fentanyl in rats with hindpaw inflammation. This decrease in running seemed to persist beyond the 3 days of assessment. These data demonstrate that fentanyl can either depress or restore activity depending on the dose and pain condition. Moreover, termination of 3 days of continuous fentanyl administration resulted in a dose and time dependent decrease in wheel running consistent with opioid withdrawal.

Medication overuse headache following repeated morphine, but not [INCREMENT]9-tetrahydrocannabinol administration in the female rat.

The potential of [INCREMENT]-tetrahydrocannabinol (THC) as a treatment for migraine depends on antinociceptive efficacy with repeated administration. Although morphine has good antinociceptive efficacy, repeated administration causes medication overuse headache (MOH) - a condition in which the intensity/frequency of migraine increases. The present study compared the effect of repeated morphine or THC administration on the magnitude and duration of migraine-like pain induced by a microinjection of allyl isothiocyanate (AITC) onto the dura mater of female rats. Acute administration of THC or morphine prevented AITC-induced depression of wheel running. This antinociception was maintained in rats treated repeatedly with THC, but not following repeated administration of morphine. Moreover, repeated morphine, but not THC administration, extended the duration of AITC-induced depression of wheel running. These data indicate that tolerance and MOH develop rapidly to morphine administration. The lack of tolerance and MOH to THC indicates that THC may be an especially effective long-term treatment against migraine.