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Preemptive intrathecal administration of endomorphins relieves inflammatory pain in male mice via inhibition of p38 MAPK signaling and regulation of inflammatory cytokines.
Abstract
BACKGROUND:Preemptive administration of analgesic drugs reduces perceived pain and
prolongs duration of antinociceptive action. Whereas several lines of evidence suggest
that endomorphins, the endogenous mu-opioid agonists, attenuate acute and chronic
pain at the spinal level, their preemptive analgesic effects remain to be determined.
In this study, we evaluated the anti-allodynic activities of endomorphins and explored
their mechanisms of action after preemptive administration in a mouse model of inflammatory
pain. METHODS:The anti-allodynic activities of preemptive intrathecal administration
of endomorphin-1 and endomorphin-2 were investigated in complete Freund's adjuvant
(CFA)-induced inflammatory pain model and paw incision-induced postoperative pain
model. The modulating effects of endomorphins on the expression of p38 mitogen-activated
protein kinase (p38 MAPK) and inflammatory mediators in dorsal root ganglion (DRG)
of CFA-treated mice were assayed by real-time reverse transcription-polymerase chain
reaction (RT-PCR), Western blotting, or immunofluorescence staining. RESULTS:Preemptive
intrathecal injection of endomorphins dose-dependently attenuated CFA-induced mechanical
allodynia via the mu-opioid receptor and significantly reversed paw incision-induced
allodynia. In addition, CFA-caused increase of phosphorylated p38 MAPK in DRG was
dramatically reduced by preemptive administration of endomorphins. Repeated intrathecal
application of the specific p38 MAPK inhibitor SB203580 reduced CFA-induced mechanical
allodynia as well. Further RT-PCR assay showed that endomorphins regulated the mRNA
expression of inflammatory cytokines in DRGs induced by peripheral inflammation. CONCLUSIONS:Our
findings reveal a novel mechanism by which preemptive treatment of endomorphins attenuates
inflammatory pain through regulating the production of inflammatory cytokines in DRG
neurons via inhibition of p38 MAPK phosphorylation.
Type
Journal articleSubject
Ganglia, SpinalNeurons
Animals
Mice
Pain
Disease Models, Animal
Inflammation
p38 Mitogen-Activated Protein Kinases
Opioid Peptides
Oligopeptides
Analgesics, Opioid
Freund's Adjuvant
Injections, Spinal
Pain Threshold
Signal Transduction
Gene Expression Regulation
Time Factors
Male
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https://hdl.handle.net/10161/18302Published Version (Please cite this version)
10.1186/s12974-018-1358-3Publication Info
Zhang, Ting; Zhang, Nan; Zhang, Run; Zhao, Weidong; Chen, Yong; Wang, Zilong; ...
Fang, Quan (2018). Preemptive intrathecal administration of endomorphins relieves inflammatory pain in
male mice via inhibition of p38 MAPK signaling and regulation of inflammatory cytokines.
Journal of neuroinflammation, 15(1). pp. 320. 10.1186/s12974-018-1358-3. Retrieved from https://hdl.handle.net/10161/18302.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Yong Chen
Associate Professor in Neurology
Dr. Yong Chen is an Associate Professor of Neurology at the Duke University School
of Medicine. He is also affiliated with Duke Anesthesiology-Center for Translational
Pain Medicine (CTPM) and Duke-Pathology.
The Chen lab mainly studies sensory neurobiology of pain and itch, with a focus on
TRP ion channels and neural circuits. The main objective of our lab is to identify
molecular and cellular mechanisms underlying chronic pain and chronic-disease associated
itch, using a combi

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