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Neural basis for the hyperalgesic action of cholecystokinin in the rostral ventromedial medulla.
J Neurophysiol. 2004 Oct; 92(4):1982-9.JN

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.

Authors+Show Affiliations

Dept. Neurological Surgery, L-472, Oregon Health and Science Univ., Portland, OR 97239, USA. heinricm@ohsu.eduNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15152023

Citation

Heinricher, Mary M., and Miranda J. Neubert. "Neural Basis for the Hyperalgesic Action of Cholecystokinin in the Rostral Ventromedial Medulla." Journal of Neurophysiology, vol. 92, no. 4, 2004, pp. 1982-9.
Heinricher MM, Neubert MJ. Neural basis for the hyperalgesic action of cholecystokinin in the rostral ventromedial medulla. J Neurophysiol. 2004;92(4):1982-9.
Heinricher, M. M., & Neubert, M. J. (2004). Neural basis for the hyperalgesic action of cholecystokinin in the rostral ventromedial medulla. Journal of Neurophysiology, 92(4), 1982-9.
Heinricher MM, Neubert MJ. Neural Basis for the Hyperalgesic Action of Cholecystokinin in the Rostral Ventromedial Medulla. J Neurophysiol. 2004;92(4):1982-9. PubMed PMID: 15152023.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neural basis for the hyperalgesic action of cholecystokinin in the rostral ventromedial medulla. AU - Heinricher,Mary M, AU - Neubert,Miranda J, Y1 - 2004/05/19/ PY - 2004/5/21/pubmed PY - 2004/12/16/medline PY - 2004/5/21/entrez SP - 1982 EP - 9 JF - Journal of neurophysiology JO - J Neurophysiol VL - 92 IS - 4 N2 - 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. SN - 0022-3077 UR - https://www.unboundmedicine.com/medline/citation/15152023/Neural_basis_for_the_hyperalgesic_action_of_cholecystokinin_in_the_rostral_ventromedial_medulla_ L2 - https://journals.physiology.org/doi/10.1152/jn.00411.2004?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -