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Titolo:
A cellular mechanism for the antinociceptive effect of a kappa opioid receptor agonist
Autore:
Ackley, MA; Hurley, RW; Virnich, DE; Hammond, DL;
Indirizzi:
Univ Chicago, Dept Anesthesia & Crit Care, Chicago, IL 60637 USA Univ Chicago Chicago IL USA 60637 esia & Crit Care, Chicago, IL 60637 USA Univ Chicago, Comm Neurobiol, Chicago, IL 60637 USA Univ Chicago Chicago IL USA 60637 , Comm Neurobiol, Chicago, IL 60637 USA
Titolo Testata:
PAIN
fascicolo: 3, volume: 91, anno: 2001,
pagine: 377 - 388
SICI:
0304-3959(200104)91:3<377:ACMFTA>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
ROSTRAL VENTROMEDIAL MEDULLA; PRESYNAPTIC INHIBITORY-ACTION; RAT SPINAL-CORD; PERIAQUEDUCTAL GRAY; IN-VITRO; MEDIATED ANTINOCICEPTION; EXCITATORY TRANSMISSION; DENTATE GYRUS; NEURONS; NUCLEUS;
Keywords:
ventromedial medulla; antinociception; kappa opioid receptor; excitatory postsynaptic current; paw-withdrawal latency; tail-flick latency;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
37
Recensione:
Indirizzi per estratti:
Indirizzo: Hammond, DL Univ Iowa, Dept Anesthesia, 200 Hawkins Dr 6JCP, Iowa City, IA52242 USA Univ Iowa 200 Hawkins Dr 6JCP Iowa City IA USA 52242 52242 USA
Citazione:
M.A. Ackley et al., "A cellular mechanism for the antinociceptive effect of a kappa opioid receptor agonist", PAIN, 91(3), 2001, pp. 377-388

Abstract

This study used concordant behavioral and electrophysiological approaches to examine the actions of the prototypic kappa opioid receptor agonist U69593 in the rostral ventromedial medulla (RVM). In vitro whole-cell voltage clamp recordings indicated that bath application of U69593 produced outward currents in primary cells in the RVM. In secondary cells, which comprised 80% of the population, U69593 produced a concentration-dependent and norbinaltorphimine (norBNI)-reversible inhibition of evoked excitatory postsynaptic currents (EPSCs) in the absence of any postsynaptic effect. U69593 also decreased the frequency, but not the amplitude of spontaneous miniature excitatory postsynaptic currents (mEPSCs) in secondary cells. The inhibition ofexcitatory inputs to secondary cells would be consonant with disinhibitionof primary cells and the production of antinociception. Consistent with this expectation, the activation of kappa opioid receptors in the RVM by microinjection of U69593 produced a dose-dependent increase in paw-withdrawal latency that was antagonized by norBNI. Furthermore, microinjection of norBNI in the RVM antagonized the increases in paw-withdrawal latency and hot-plate latency produced by systemically-administered U69593. In contrast, microinjection of norBNI in the RVM did not antagonize the increase in tail-flick latency produced by systemically-administered U69593. Also, microinjection of U69593 in the RVM did not increase tail-flick latency. The highly test-dependent nature of U69593's effects suggests that the mechanisms by which neurons in the RVM modulate thermal nociceptive responses evoked from thetail and hindpaw are not uniform. Collectively, these data suggest that the RVM is a primary site of action for the antinociceptive actions of kappa opioid receptor agonists and that the mechanism most likely involves a presynaptic inhibition of excitatory inputs to secondary cells. Thus, disinhibition of pain inhibitory neurons in the RVM is likely to be a common mechanism by which opioid receptor agonists produce antinociception, whether by the direct inhibition of inhibitory secondary cells, as in the case of mu opioid receptor agonists, or by a reduction in the excitatory drive to these neurons, as in the case of kappa opioid receptor agonists. Copyright (C) 2001 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 15/08/20 alle ore 19:05:49