Neural Basis for the Hyperalgesic Action of Cholecystokinin in the Rostral Ventromedial Medulla
- 1 October 2004
- journal article
- Published by American Physiological Society in Journal of Neurophysiology
- Vol. 92 (4) , 1982-1989
- https://doi.org/10.1152/jn.00411.2004
Abstract
The analgesic actions of opioids can be modified by endogenous “anti-opioid” peptides, among them cholecystokinin (CCK). CCK is now thought to have a broader, pronociceptive role, and contributes to hyperalgesia in inflammatory and neuropathic pain states. The aim of this study was to determine whether anti-opioid and pronociceptive actions of CCK have a common underlying mechanism. We showed previously that a low dose of CCK microinjected into the rostral ventromedial medulla (RVM) blocked the analgesic effect of systemically administered morphine by preventing activation of off-cells, which are the antinociceptive output of this well characterized pain-modulating region. At this anti-opioid dose, CCK had no effect on the spontaneous activity of these neurons or on the activity of on-cells (hypothesized to facilitate nociception) or “neutral cells” (which have no known role in pain modulation). In this study, we used microinjection of a higher dose of CCK into the RVM to test whether activation of on-cells could explain the pronociceptive action of this peptide. Paw withdrawal latencies to noxious heat and the activity of a characterized RVM neuron were recorded in rats lightly anesthetized with methohexital. CCK (30 ng/200 nl) activated on-cells selectively and produced behavioral hyperalgesia. Firing of off-cells and neutral cells was unaffected. These data show that direct, selective activation of RVM on-cells by CCK is sufficient to produce thermal hyperalgesia and indicate that the anti-opioid and pronociceptive effects of this peptide are mediated by actions on different RVM cell classes.Keywords
This publication has 64 references indexed in Scilit:
- Mechanisms of opioid-induced pain and antinociceptive tolerance: descending facilitation and spinal dynorphinPain, 2001
- The role of excitatory amino acid transmission within the rostral ventromedial medulla in the antinociceptive actions of systemically administered morphinePain, 1999
- Extracellular cholecystokinin levels in the rat spinal cord following chronic morphine exposure: an in vivo microdialysis studyBrain Research, 1999
- CCKB receptors in the periaqueductal grey are involved in electroacupuncture antinociception in the rat cold water tail-flick testNeuropharmacology, 1998
- A Neuronal Correlate of Secondary Hyperalgesia in the Rat Spinal Dorsal Horn Is Submodality Selective and Facilitated by Supraspinal InfluenceExperimental Neurology, 1998
- Antiallodynic effects of a CCKB antagonist in rats with nerve ligation injury: role of endogenous enkephalinsNeuroscience Letters, 1996
- Chronic pain-related behaviors in spinally injured rats: Evidence for functional alterations of the endogenous cholecystokinin and opioid systemsPain, 1994
- Hyperalgesia during Naloxone-Precipitated Withdrawal from Morphine Is Associated with Increased On-Cell Activity in the Rostral Ventromedial MedullaSomatosensory & Motor Research, 1990
- Cholecystokinin-octapeptide antagonizes morphine analgesia in periaqueductal gray of the ratBrain Research, 1989
- Putative Nociceptive Modulatory Neurons in the Rostral Ventromedial Medulla of the Rat Display Highly Correlated Firing PatternsSomatosensory & Motor Research, 1989