Effects of intraplantar morphine on paw edema and pain-related behaviour in a rat model of repeated acute inflammation

Recent studies suggest that peripheral morphine may represent a valuable treatment in inflammatory painful diseases. This study examined effects of intraplantar morphine against noxious pressure and paw edema in rats with repeated acute inflammation induced by two carrageenin injections 7 days apart. This model mimics at least partly some aspects of recurrent inflammatory pain encountered in the clinical situation. In the first part of the experiment, the effect of intraplantar morphine into the inflamed hindpaw was determined 3 h after carrageenin injection. Intraplantar morphine (50–200 μg) produced significant elevations of vocalization thresholds to paw pressure in inflamed but not in non-inflamed paws after both carrageenin injection; these effects were reversible by intraplantar naloxone methiodide (40 μg). The effects of intraplantar morphine (150 μg) were similar in magnitude to that of intravenous morphine (1 mg/kg) after first carrageenin injection. In contrast, at doses of 150–200 μg, they were significantly lower after second ipsilateral carrageenin injection 7 days later, than first injection. Intraplantar morphine (100–200 μg) had no effect on paw edema associated with both carrageenin injections. In the second part of the experiment, intraplantar morphine was injected 10 min before the first injection of carrageenin. Intraplantar morphine (50 μg) was ineffective, whereas morphine (100–200 μg) prevented reduction of vocalization thresholds to paw pressure of inflamed hindpaw for 3 h. The intraplantar injection of morphine (100 and 150 μg) produced a transient increase in the volume of inflamed hindpaw, not reversible by intraplantar naloxone methiodide (40 μg). Pretreatment with intraplantar morphine had no effect on reduction of vocalization thresholds to paw pressure and edema related to a second ipsilateral injection of carrageenin 7 days later. These findings suggest that peripheral morphine may be useful for the clinical management of acute inflammatory pain rather than in recurrent inflammatory painful situations.