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Individual differences in acute pain-induced endogenous analgesia predict time to resolution of postoperative pain in the rat.

Abstract：

BACKGROUND:Chronic postsurgical pain, a significant public health problem, occurs in 10 to 50% of patients undergoing major surgery. Acute pain induces endogenous analgesia termed conditioned pain modulation (CPM), and the strength of CPM preoperatively predicts the likelihood of chronic postsurgical pain. The relation between CPM and recovery from surgery has not been examined in preclinical models. METHODS:CPM was assessed in individual rats and correlated with each animal's time course of recovery of hypersensitivity after partial spinal nerve ligation. The role of descending noradrenergic pathways in the spinal cord to mechanisms of CPM and recovery was tested using idazoxan to block noradrenergic receptors or antidopamine β-hydroxylase-conjugated saporin to ablate these pathways. Behavioral hypersensitivity, static weight bearing, and spinal glial activation were measured after partial spinal nerve ligation. RESULTS:The strength of CPM varied over two-fold between individuals and was directly correlated with the slope of recovery from hypersensitivity after surgery (P < 0.0001; r = 0.660). CPM induced the release of norepinephrine in the spinal cord and was partially blocked by intrathecal idazoxan or dopamine β-hydroxylase-saporin. Dopamine β-hydroxylase-saporin also slowed recovery and enhanced spinal glial activation after partial spinal nerve ligation surgery. Ongoing activation of these pathways was critical to sustained recovery because intrathecal dopamine β-hydroxylase-saporin given 7 weeks after recovery reinstituted hypersensitivity, while having no effect in animals without previous surgery. CONCLUSION:Collectively, these studies provide a clear back-translation from clinical observations of CPM and chronic postsurgical pain and suggest that the ability to engage ongoing descending endogenous noradrenergic signaling may be critical in determining time course of recovery from hypersensitivity after surgery.

journal_name

Anesthesiology

journal_title

Anesthesiology

authors

Peters CM,Hayashida K,Suto T,Houle TT,Aschenbrenner CA,Martin TJ,Eisenach JC

doi

10.1097/ALN.0000000000000593

subject

Has Abstract

pub_date

2015-04-01 00:00:00

pages

895-907

issue

eissn

0003-3022

issn

1528-1175

journal_volume

122

pub_type

杂志文章

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Individual differences in acute pain-induced endogenous analgesia predict time to resolution of postoperative pain in the rat.