The Medullary Dorsal Horn

Abstract

Pruritus is a common side effect of epidural and intrathecal morphine administration in humans. This naloxone-reversible pruritus is typically present on the trunk, but is often severe around the eyes and nose, of the patients. The brain stem has been proposed as the site where opioids act to produce this effect. The authors studied the effect of morphine administered into the medullary dorsal horn (MDH), the brain stem homologue of the spinal dorsal horn, on facial-scratching behavior in monkeys. Morphine was unilaterally microinjected into the MDH of rhesus monkeys. Systemic injections of the opioid-receptor antagonist naloxone (0.5 mg/kg intramuscularly) were also made in combination with morphine microinjection. Systemic injections of the antihistamine chlorcyclizine (1.0 and 2.5 mg/kg intramuscularly) were also made to determine if facial scratching was mediated through histamine release. The monkeys were videotaped for 10-15 min before and 1-2 h after opioid microinjection, and the number and location of scratches were counted. A dose-response curve was established for the mu/delta-opioid-receptor agonist morphine (0.5, 1.0, 2.5, and 5.0 micrograms). Specificity of the site of action within the MDH was examined by systematically changing the microinjection site, and examining the area of the face that the monkeys scratched. Morphine produced large dose-dependent increases in facial scratching ipsilateral to the microinjection. Increases in facial scratching were also observed contralateral to the microinjections. These effects were reversed by naloxone. The facial area scratched after microinjection of morphine was directly related to the injection site, with 1-mm changes in the location of the microinjection resulting in pronounced changes in the area of the face that the monkeys scratched. Systemic injection of chlorcyclizine produced only a small, transient attenuation of morphine's effect. Data from this study demonstrate that the MDH is a site where morphine acts to produce facial scratching in monkeys by acting at opioid receptors. It is also likely that the MDH is a site where centrally administered opioids act in producing facial pruritus in humans. The effects of morphine on facial-scratching behavior were only modestly attenuated with chlorcyclizine, indicating a minor involvement of a histamine-dependent mechanism of action.