| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
The Journal of Neurophysiology Vol. 78 No. 6 December 1997,
pp. 3351-3358
Copyright ©1997 The American Physiological Society
1 Division of Neurosurgery, 2 Department of Physiology and Pharmacology, and 3 Vollum Institute, Oregon Health Sciences University, Portland, Heinricher, M. M., S. McGaraughty, and D. K. Grandy. Circuitry underlying antiopioid actions of orphanin FQ in the rostral ventromedial medulla. J. Neurophysiol. 78: 3351-3358, 1997. Several laboratories recently identified a 17 amino-acid peptide, termed "nociceptin" or "orphanin FQ (OFQ)", as the endogenous ligand for the LC132 (or "opioid receptor-like1") receptor. Taken together with the fact that the cellular effects of OFQ are to a large extent opioid-like, the close relationship between the LC132 receptor and known opioid receptors raised expectations that the behavioral effects of this peptide would resemble those of opioids. However studies of the role of OFQ in nociception have not provided a unified view. The aim of the present study was to use a combination of electrophysiological and pharmacological techniques to characterize the actions of OFQ in a brain region in which the circuitry mediating the analgesic actions of opioids has been relatively well characterized, the rostral ventromedial medulla (RVM). Single-cell recording was combined with opioid administration and local infusion of OFQ in the RVM of rats lightlyanesthetized with barbiturates. The tail flick reflex was used as a behavioral index of nociceptive responsiveness. Two classes of physiologically identifiable RVM neurons with distinct responses to opioids have been characterized. OFF-cells are activated, although indirectly, by opioids, and there is strong evidence that this activation is crucial to opioid antinociception. ON-cells, thought to enable nociception, are directly inhibited by opioids. Cells of a third class, NEUTRAL cells, do not respond to opioids and whether or not they have any role in nociceptive modulation remains an open question. OFQ infused within the RVM profoundly suppressed the firing of all classes of RVM neurons, blocking opioid-induced activation of OFF-cells. The antinociceptive effects of a µ-opioid agonist infused at the same site were significantly attenuated in these animals. Those of systemically administered morphine, which can produce its antinociceptive effects by acting at a number of CNS sites, were not blocked by RVM OFQ. Inasmuch as activation of OFF-cells can account for the antinociceptive action of opioids within the RVM, these results demonstrate that, at least within the medulla, OFQ can exert a functional "antiopioid" effect by suppressing firing of this cell class. However to the extent that antinociceptive and pronociceptive outflows from various brain regions involved in both transmission and modulation of nociception are active under different conditions, focal application of OFQ in different regions could potentially produce either hypalgesia or hyperalgesia.
This article has been cited by other articles:
|
|
 |
|
  A. S. Quevedo and R. C. Coghill Attentional Modulation of Spatial Integration of Pain: Evidence for Dynamic Spatial Tuning J. Neurosci., October 24, 2007; 27(43): 11635 - 11640. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Claiborne, S. Nag, and S. S. Mokha Activation of Opioid Receptor Like-1 Receptor in the Spinal Cord Produces Sex-Specific Antinociception in the Rat: Estrogen Attenuates Antinociception in the Female, whereas Testosterone Is Required for the Expression of Antinociception in the Male J. Neurosci., December 13, 2006; 26(50): 13048 - 13053. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Crisostomo, P. Li, S. C. Tjen-A-Looi, and J. C. Longhurst Nociceptin in rVLM mediates electroacupuncture inhibition of cardiovascular reflex excitatory response in rats J Appl Physiol, June 1, 2005; 98(6): 2056 - 2063. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. D. Mandyam, D. R. Thakker, and K. M. Standifer {micro}-Opioid-Induced Desensitization of Opioid Receptor-Like 1 and {micro}-Opioid Receptors: Differential Intracellular Signaling Determines Receptor Sensitivity J. Pharmacol. Exp. Ther., September 1, 2003; 306(3): 965 - 972. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. U. Zeilhofer and G. Calo Nociceptin/Orphanin FQ and Its Receptor--Potential Targets for Pain Therapy? J. Pharmacol. Exp. Ther., August 1, 2003; 306(2): 423 - 429. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Meis Nociceptin/Orphanin FQ: Actions within the Brain Neuroscientist, April 1, 2003; 9(2): 158 - 168. [Abstract] [PDF]
|
|
|
|
|
|
C. D. Mandyam, D. R. Thakker, J. L. Christensen, and K. M. Standifer Orphanin FQ/Nociceptin-Mediated Desensitization of Opioid Receptor-Like 1 Receptor and {micro} Opioid Receptors Involves Protein Kinase C: A Molecular Mechanism for Heterologous Cross-Talk J. Pharmacol. Exp. Ther., August 1, 2002; 302(2): 502 - 509. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Meis, T. Munsch, and H.-C. Pape Antioscillatory Effects of Nociceptin/Orphanin FQ in Synaptic Networks of the Rat Thalamus J. Neurosci., February 1, 2002; 22(3): 718 - 727. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Mogil and G. W. Pasternak The Molecular and Behavioral Pharmacology of the Orphanin FQ/Nociceptin Peptide and Receptor Family Pharmacol. Rev., September 1, 2001; 53(3): 381 - 415. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. M. Heinricher, S. McGaraughty, and V. Tortorici Circuitry Underlying Antiopioid Actions of Cholecystokinin Within the Rostral Ventromedial Medulla J Neurophysiol, January 1, 2001; 85(1): 280 - 286. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Ueda, M. Inoue, H. Takeshima, and Y. Iwasawa Enhanced Spinal Nociceptin Receptor Expression Develops Morphine Tolerance and Dependence J. Neurosci., October 15, 2000; 20(20): 7640 - 7647. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
