Molecular and cellular mechanisms of the age-dependency of opioid analgesia and toleranceReport as inadecuate




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Molecular Pain

, 8:38

First Online: 21 May 2012Received: 30 November 2011Accepted: 09 May 2012

Abstract

The age-dependency of opioid analgesia and tolerance has been noticed in both clinical observation and laboratory studies. Evidence shows that many molecular and cellular events that play essential roles in opioid analgesia and tolerance are actually age-dependent. For example, the expression and functions of endogenous opioid peptides, multiple types of opioid receptors, G protein subunits that couple to opioid receptors, and regulators of G protein signaling RGS proteins change with development and age. Other signaling systems that are critical to opioid tolerance development, such as N-methyl-D-aspartic acid NMDA receptors, also undergo age-related changes. It is plausible that the age-dependent expression and functions of molecules within and related to the opioid signaling pathways, as well as age-dependent cellular activity such as agonist-induced opioid receptor internalization and desensitization, eventually lead to significant age-dependent changes in opioid analgesia and tolerance development.

KeywordsMolecular and cellular mechanisms Age-dependency Opioid tolerance AbbreviationsRGSregulators of G protein signaling

NMDAN-methyl-D-aspartic acid

VASvisual analog scale

DRGdorsal root ganglion

ORL1opioid receptor-like 1

GPCRG protein-coupled, seven-transmembrane receptor superfamily

ACadenylyl cyclase

cAMPcyclic AMP

MAPKmitogen-activated protein kinase

GRKsG protein-coupled receptor kinases

MORμ-opioid receptor

PAGperiaqueductal grey matter

EGFepidermal growth factor

IL2interleukin 2

PKCprotein kinase C

CCKcholecystokinin

NPFFneuropeptide FF

PrRPprolactin-releasing peptide

COXcyclooxygenase

CGRPcalcitonin gene-related peptide

mGluRsmetabotropic glutamate receptors

NPYneuropeptide Y

SPsubstance P

GAPGTPase-accelerating protein.

Electronic supplementary materialThe online version of this article doi:10.1186-1744-8069-8-38 contains supplementary material, which is available to authorized users.

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Author: Jing Zhao - Xin Xin - Guo-xi Xie - Pamela Pierce Palmer - Yu-guang Huang

Source: https://link.springer.com/







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