Participation of the descending noradrenergic inhibitory system in the anti-hyperalgesic effect of acetaminophen in a rat model of inflammation

This study investigated the relationship between the analgesic efficacy of acetaminophen and the descending noradrenergic systems using rodent models of inflammatory pain. Inflammatory pain models were established by carrageenan injection into rats' paws. The models were defined as acute (4 h a...

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Bibliographic Details
Published in:Life sciences (1973) 2021-12, Vol.286, p.120030-120030, Article 120030
Main Authors: Juri, Takashi, Fujimoto, Yohei, Suehiro, Koichi, Nishikawa, Kiyonobu, Mori, Takashi
Format: Article
Language:English
Subjects:
Acetaminophen
Acetaminophen - pharmacology
Acetaminophen - therapeutic use
AM404
Analgesics
Animal models
Animals
Carrageenan
Carrageenan - administration & dosage
Carrageenans
Descending noradrenergic inhibitory system
Disease Models, Animal
Hyperalgesia - drug therapy
Inflammation
Inflammation - chemically induced
Inflammation - drug therapy
Inflammatory pain
Injection
Intracerebroventricular administration
Intravenous administration
Locus coeruleus
Locus Coeruleus - drug effects
Locus Coeruleus - metabolism
Male
Mechanical stimuli
Metabolites
Microdialysis
Noradrenaline
Norepinephrine
Norepinephrine - antagonists & inhibitors
Pain
Pain perception
Rats
Rats, Sprague-Dawley
Spinal Cord - drug effects
Spinal Cord - metabolism
Subacute pain
Yohimbine
Yohimbine - pharmacology
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Summary:This study investigated the relationship between the analgesic efficacy of acetaminophen and the descending noradrenergic systems using rodent models of inflammatory pain. Inflammatory pain models were established by carrageenan injection into rats' paws. The models were defined as acute (4 h after carrageenan injection), subacute (24 h after carrageenan injection), and late (1 week after carrageenan injection) phase. To evaluate intravenous acetaminophen treatment, the withdrawal threshold to mechanical stimuli was assessed simultaneously with in vivo microdialysis assay of noradrenaline levels in the locus coeruleus (LC). Further analyses were performed to observe the effect of yohimbine on the treatment and the impact of AM404 treatment, a metabolite of acetaminophen, on noradrenaline levels in the LC. In all phases, intravenous acetaminophen had a significant anti-hyperalgesic effect (p 
ISSN:0024-3205
1879-0631
DOI:10.1016/j.lfs.2021.120030