Cellular mechanism for anti-analgesic action of agonists of the κ-opioid receptor

Z. Z. Pan (), S. A. Tershner and H. L. Fields
Additional contact information
Z. Z. Pan: the W. M. Keck Center for Integrative Neuroscience
S. A. Tershner: the W. M. Keck Center for Integrative Neuroscience
H. L. Fields: the W. M. Keck Center for Integrative Neuroscience

Nature, 1997, vol. 389, issue 6649, 382-385

Abstract: Abstract The analgesic effect of clinically used exogenous opioids, such as morphine, is mediated primarily through μ-opioid receptors1,2,3, but the function of the κ-receptor in opioid analgesia is unclear. Although κ-receptor agonists can produce analgesia4,5, behavioural studies indicate that κ agonists applied intravenously or locally into the spinal cord antagonize morphine analgesia (see refs 4, 6 for reviews). As morphine, a primary μ agonist1, also binds to κ-receptors7 and the analgesic effectiveness of morphine decreases with repeated use (tolerance), it is important to understand the mechanism for the functional interaction between κ- and μ-opioid receptors in the central nervous system. Here we present in vitro electrophysiological and in vivo behavioural evidence that activation of the κ-receptor specifically antagonizes μ-receptor-mediated analgesia. We show that in slice preparations of a rat brainstem nucleus, which is critical for the action of opioids in controlling pain, functional κ- and μ-receptors are each localized on physiologically different types of neuron. Activation of the κ-receptor hyperpolarizes neurons that are activated indirectly by the μ-receptor. In rats, κ-receptor activation in this brainstem nucleus significantly attenuates local μ-receptor-mediated analgesia. Our findings suggest a new cellular mechanism for the potentially ubiquitous opposing interaction between μ- and κ-opioid receptors and may help in the design of treatments for pain.

Date: 1997
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/38730 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:389:y:1997:i:6649:d:10.1038_38730

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/38730

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().