Noradrenergic and opioid systems interact to alter the detection of noxious thermal stimuli and facial scratching in monkeys.
We examined the ability of the alpha 2-adrenoceptor agonist, ST-91, microinjected into the medullary dorsal horn (MDH), to diminish the sensory-discriminative features of noxious heat stimuli in awake behaving monkeys. Two monkeys performed a noxious thermal detection task and the time to detection of small increases in heat served as a measure of the perceived intensity of pain. ST-91 microinjected into the MDH (1.0, 3.0, 10.0 and 30.0 micrograms/0.4 microliter) produced dose-dependent increases in detection time to graded temperature increases (0.4-1.0 degrees C) from a noxious 46 degrees C base line. These dose-dependent effects were attenuated by the systemic administration of the alpha 2-adrenoceptor antagonist, idazoxan (2.0 mg/kg, i.m.), but not by the alpha 1-adrenoceptor antagonist, prazosin (0.5 mg/kg, i.m.) or the opioid-receptor antagonist, naloxone (0.5 mg/kg, i.m.). The effect of ST-91 on detection latency of thermal stimuli was not the result of alterations in attentional, motivational or motoric aspects of the monkeys' behavior, because detection of visual stimuli and non-noxious temperature coolings (36.0-34.5 degrees C) in a similar paradigm were not consistently altered. Microinjection of morphine (3.0 mg) into the MDH also increased detection latency of the noxious heat stimuli. Systemic administration of the opioid-receptor antagonist, naloxone (0.5 mg/kg), and the alpha 2-adrenoceptor antagonist, idazoxan (2.0 mg/kg, i.m.) attenuated these effects of morphine. In a separate experiment, morphine (5.0 micrograms) microinjected into the MDH induced facial scratching behavior. Idazoxan (2.0 mg/kg) was effective at attenuating this scratching behavior.(ABSTRACT TRUNCATED AT 250 WORDS)
Thomas
David A
DA
Neurobiology and Anesthesiology Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892 USA.
Anton
Fernand
F
Kenshalo
Daniel R
DR
Williams
Gene M
GM
Dubner
Ronald
R
D018674:Adrenergic Antagonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology; D004594:Electrophysiology; D006358:Hot Temperature; D019329:Idazoxan; D008252:Macaca fascicularis; D008253:Macaca mulatta; D008297:Male; D008526:Medulla Oblongata / Q000502:physiology; D008845:Microinjections; D009270:Naloxone / Q000494:pharmacology; D009638:Norepinephrine / Q000502:physiology*; D010146:Pain / Q000523:psychology*; D010812:Physical Stimulation; D011957:Receptors, Opioid / Q000502:physiology*
D018674:Adrenergic Antagonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D011957:Receptors, Opioid; D009270:Naloxone; C011266:ST 91; D003000:Clonidine; D009638:Norepinephrine; D019329:Idazoxan