A cellular mechanism for the bidirectional pain-modulating actions of orphanin FQ/nociceptin

Zhizhong Z. Pan; Naomi Hirakawa; Howard L. Fields

doi:10.1016/S0896-6273(00)81183-6

A cellular mechanism for the bidirectional pain-modulating actions of orphanin FQ/nociceptin

Zhizhong Z. Pan, Naomi Hirakawa, Howard L. Fields

Research output: Contribution to journal › Article › peer-review

145 Scopus citations

Abstract

Orphanin FQ/nociceptin (OFQ/N) and its receptor share substantial structural features and cellular actions with classic opioid peptides and receptors, but have distinct pharmacological profiles and behavioral effects. Currently there is an active debate about whether OFQ/N produces hyperalgesia or analgesia. Using a well-defined brainstem pain-modulating circuit, we show that OFQ/N can cause either an apparent hyperalgesia by antagonizing μ opioid-induced analgesia or a net analgesic effect by reducing the hyperalgesia during opioid abstinence. It presumably produces these two opposite actions by inhibiting two distinct groups of neurons whose activation mediates the two effects of opioid administration. OFQ/N antagonism of the hyperalgesia may have significance for the treatment of opioid withdrawal and sensitized pain.

Original language	English (US)
Pages (from-to)	515-522
Number of pages	8
Journal	Neuron
Volume	26
Issue number	2
DOIs	https://doi.org/10.1016/S0896-6273(00)81183-6
State	Published - 2000
Externally published	Yes

ASJC Scopus subject areas

General Neuroscience

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10.1016/S0896-6273(00)81183-6

Cite this

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title = "A cellular mechanism for the bidirectional pain-modulating actions of orphanin FQ/nociceptin",

abstract = "Orphanin FQ/nociceptin (OFQ/N) and its receptor share substantial structural features and cellular actions with classic opioid peptides and receptors, but have distinct pharmacological profiles and behavioral effects. Currently there is an active debate about whether OFQ/N produces hyperalgesia or analgesia. Using a well-defined brainstem pain-modulating circuit, we show that OFQ/N can cause either an apparent hyperalgesia by antagonizing μ opioid-induced analgesia or a net analgesic effect by reducing the hyperalgesia during opioid abstinence. It presumably produces these two opposite actions by inhibiting two distinct groups of neurons whose activation mediates the two effects of opioid administration. OFQ/N antagonism of the hyperalgesia may have significance for the treatment of opioid withdrawal and sensitized pain.",

author = "Pan, {Zhizhong Z.} and Naomi Hirakawa and Fields, {Howard L.}",

note = "Funding Information: We thank Dr. Roger Nicoll for comments on the manuscript and Josh Johansen for assistance with histology. This work was supported by grants from the National Institute of Drug Abuse and from the UCSF Committee on Research.",

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AU - Pan, Zhizhong Z.

AU - Hirakawa, Naomi

AU - Fields, Howard L.

N1 - Funding Information: We thank Dr. Roger Nicoll for comments on the manuscript and Josh Johansen for assistance with histology. This work was supported by grants from the National Institute of Drug Abuse and from the UCSF Committee on Research.

PY - 2000

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N2 - Orphanin FQ/nociceptin (OFQ/N) and its receptor share substantial structural features and cellular actions with classic opioid peptides and receptors, but have distinct pharmacological profiles and behavioral effects. Currently there is an active debate about whether OFQ/N produces hyperalgesia or analgesia. Using a well-defined brainstem pain-modulating circuit, we show that OFQ/N can cause either an apparent hyperalgesia by antagonizing μ opioid-induced analgesia or a net analgesic effect by reducing the hyperalgesia during opioid abstinence. It presumably produces these two opposite actions by inhibiting two distinct groups of neurons whose activation mediates the two effects of opioid administration. OFQ/N antagonism of the hyperalgesia may have significance for the treatment of opioid withdrawal and sensitized pain.

AB - Orphanin FQ/nociceptin (OFQ/N) and its receptor share substantial structural features and cellular actions with classic opioid peptides and receptors, but have distinct pharmacological profiles and behavioral effects. Currently there is an active debate about whether OFQ/N produces hyperalgesia or analgesia. Using a well-defined brainstem pain-modulating circuit, we show that OFQ/N can cause either an apparent hyperalgesia by antagonizing μ opioid-induced analgesia or a net analgesic effect by reducing the hyperalgesia during opioid abstinence. It presumably produces these two opposite actions by inhibiting two distinct groups of neurons whose activation mediates the two effects of opioid administration. OFQ/N antagonism of the hyperalgesia may have significance for the treatment of opioid withdrawal and sensitized pain.

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A cellular mechanism for the bidirectional pain-modulating actions of orphanin FQ/nociceptin

Abstract

ASJC Scopus subject areas

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