Peripheral antihyperalgesic effect of morphine to heat, but not mechanical, stimulation in healthy volunteers after ultraviolet-B irradiation

The objective of this study was to evaluate direct peripheral analgesic eff ects of morphine using a peripheral model of hyperalgesia and the technique of TV regional anesthesia (NRA), thus allowing the differentiation between central and peripheral mechanisms of action. Two spots on the ventral side s of both forearms in 12 volunteers were irradiated with ultraviolet (UV)-B to induce thermal and mechanical hyperalgesia. One day after the induction of the inflammatory reaction, 40 mt of morphine hydrochloride 0.01% was ad ministered via IVRA. Calibrated heat and phasic mechanical stimuli were app lied to differentially determine impairments of tactile and nociceptive per ception. Touch and phasic mechanical stimuli of noxious intensity to normal skin did not reveal altered responsiveness caused by morphine. Ln contrast , the administration of morphine significantly increased heat pain threshol ds in the UV-B-pretreated skin areas. The peripheral antihyperalgesic effec ts of morphine were demonstrated only in inflamed skin areas. Direct centra l analgesic effects were ruled out by the lack of measurable plasma concent rations of morphine and its metabolites. Morphine 0.01% significantly dimin ished thermal, but not mechanical, hyperalgesia by a peripheral mode of act ion, which suggests inhibition of effector pathways leading to heat, but no t mechanical, sensitization. Implications: The peripheral analgesic effects of morphine were studied using modified TV regional anesthesia. When admin istered 1 day after the induction of dermal inflammation, morphine 0.01% di minished heat, but not primary mechanical, hyperalgesia. Therefore, suppres sion of mechanical hyperalgesia seen in previous studies could be predomina ntly due to inhibition of secondary (central) mechanical hyperalgesia.