THE PERIPHERAL ANTINOCICEPTIVE EFFECT OF MORPHINE IN A RAT MODEL OF FACIAL-PAIN

The present study compared the peripheral and systemic antinociceptive effect of morphine on formalin-induced facial pain behavior in the ra t. Formalin (5%, 50 mu l) was injected subcutaneously into the vibriss al pad of adult rats (250-300 g). Morphine sulfate at doses of 100-100 0 mu g was subcutaneously injected locally (same area) or systemically (in the neck), 30 min before, or simultaneously with, formalin. The t ypical biphasic face grooming response, consisting of an early phasic phase (0-6 min) and a delayed tonic phase (12-42 min), displayed by co ntrol animals, was suppressed by both local and systemic administratio n of morphine; this effect was dose dependent. However, the suppressio n of the early phase with local morphine administration 30 min before formalin could be significantly greater (49-52%) than with systemic ad ministration, depending on the dose used. Administration of local morp hine simultaneously with formalin produced up to 34% reduction in the early and an additional 32% reduction of the late phases of Face groom ing, compared to systemic injections. Local injection of naloxone (10 mu g) almost completely reversed the antinociceptive effect of 1000 mu g of morphine (early phase 85 +/- 7%, late phase 100 +/- 26% reductio n), whereas the same dose of naloxone applied systemically (i.p.) prod uced only partial reversal (early phase 29 +/- 16%, late phase 36 +/- 1% reduction). This study further indicates that locally administered morphine can exert an analgesic effect superior to systemic administra tion in the case of inflammatory and non-inflammatory pain through a p eripheral site of action. These results support the clinical use of pe ripheral opioid administration in the treatment of human painful condi tions.