A medial prefrontal cortex-nucleus acumens corticotropin-releasing factor circuitry for neuropathic pain-increased susceptibility to opioid reward

Translational Psychiatry
Yuanzhong KaiWenjuan Tao

Abstract

Recent studies have shown that persistent pain facilitates the response to morphine reward. However, the circuit mechanism underlying this process remains ambiguous. In this study, using chronic constriction injury (CCI) of the sciatic nerve in mice, we found that persistent neuropathic pain reduced the minimum number of morphine conditioning sessions required to induce conditioned place preference (CPP) behavior. This dose of morphine had no effect on the pain threshold. In the medial prefrontal cortex (mPFC), which is involved in both pain and emotion processing, corticotropin-releasing factor (CRF) expressing neuronal activity was increased in CCI mice. Chemogenetic inhibition of mPFC CRF neurons reversed CCI-induced morphine CPP facilitation. Furthermore, the nucleus acumens (NAc) received mPFC CRF functional projections that exerted excitatory effects on NAc neurons. Optogenetic inhibition of mPCF neuronal terminals or local infusion of the CRF receptor 1 (CRFR1) antagonist in the NAc restored the effects of neuropathic pain on morphine-induced CPP behavior, but not in normal mice. On a molecular level, in CCI mice, CRFR1 protein expression was increased in the NAc by a histone dimethyltransferase G9a-mediated epigenetic m...Continue Reading

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Citations

Jul 19, 2019·Neurochemical Research·Priscila MedeirosNorberto Cysne Coimbra
Jun 12, 2020·Physiological Reviews·Rohini Kuner, Thomas Kuner
Nov 17, 2020·Frontiers in Behavioral Neuroscience·Dakota F Brockway, Nicole A Crowley
Jun 24, 2020·Peptides·Richard J Bodnar

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Methods Mentioned

BETA
protein assay
immunoprecipitation
ChIP
PCR

Software Mentioned

Clampfit
GraphPad Prism
BrainVTA
OriginPro

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