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

Abstract

The objective of this study was to evaluate direct peripheral analgesic effects of morphine using a peripheral model of hyperalgesia and the technique of IV regional anesthesia (IVRA), thus allowing the differentiation between central and peripheral mechanisms of action. Two spots on the ventral sides 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 mL of morphine hydrochloride 0.01% was administered via IVRA. Calibrated heat and phasic mechanical stimuli were applied to differentially determine impairments of tactile and nociceptive perception. Touch and phasic mechanical stimuli of noxious intensity to normal skin did not reveal altered responsiveness caused by morphine. In contrast, the administration of morphine significantly increased heat pain thresholds in the UV-B-pretreated skin areas. The peripheral antihyperalgesic effects of morphine were demonstrated only in inflamed skin areas. Direct central analgesic effects were ruled out by the lack of measurable plasma concentrations of morphine and its metabolites. Morphine 0.01% significantly diminished thermal, but not mechanical, hyperalgesia by a peripheral mode of action, which suggests inhibition of effector pathways leading to heat, but not mechanical, sensitization.

Implications: The peripheral analgesic effects of morphine were studied using modified IV regional anesthesia. When administered 1 day after the induction of dermal inflammation, morphine 0.01% diminished heat, but not primary mechanical, hyperalgesia. Therefore, suppression of mechanical hyperalgesia seen in previous studies could be predominantly due to inhibition of secondary (central) mechanical hyperalgesia.