Hyperalgesia during acute opioid abstinence: evidence for a nociceptive facilitating function of the rostral ventromedial medulla.
Naloxone-precipitated opioid abstinence is associated with enhancement of reflex responses to noxious stimulation (hyperalgesia). The present experiments in lightly anesthetized rats were designed to determine (1) whether neurons in the rostral ventromedial medulla (RVM) contribute to this enhancement, and (2) whether this enhancement is due to removal of an inhibitory modulatory influence or to activation of a facilitatory influence. In the first experiment, 10 micrograms of morphine was microinjected into the RVM; subsequent administration of naloxone (1 mg/kg, i.v.) shortened tail-flick latency. This is evidence that a synaptic action of opioids within the RVM can contribute to hyperalgesia. In the second experiment, systemic administration of morphine (2 mg/kg, i.v.) was followed by systemic administration of naloxone (1 mg/kg, i.v.), which produced a significant hyperalgesia that could be markedly attenuated by microinjection of 10 micrograms lidocaine into the RVM. That inactivation of RVM reduces the hyperalgesia indicates that the CNS is capable of generating a facilitating action on nociceptive transmission. Previous studies from this laboratory have indicated that a population of RVM neurons, on-cells, shows increased activity during opioid abstinence. The present experiments support the hypothesis that RVM on-cells exert a facilitating influence on nociceptive transmission.
Kaplan
H
H
Department of Neurology, University of California, San Francisco 94143.
Fields
H L
HL
D000818:Animals; D008012:Lidocaine / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000502:physiology* / Q000503:physiopathology; D008845:Microinjections; D009270:Naloxone / Q000008:administration & dosage / Q000494:pharmacology*; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology*; D010146:Pain / Q000503:physiopathology*; D051381:Rats; D011919:Rats, Inbred Strains; D012881:Skin Temperature / Q000187:drug effects; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*
D009270:Naloxone; D008012:Lidocaine