PMID- 31129808
OWN - NLM
STAT- MEDLINE
DCOM- 20200406
LR  - 20210109
IS  - 1559-1182 (Electronic)
IS  - 0893-7648 (Print)
IS  - 0893-7648 (Linking)
VI  - 56
IP  - 12
DP  - 2019 Dec
TI  - Opioid-Induced Hyperalgesia Is Associated with Dysregulation of Circadian Rhythm 
      and Adaptive Immune Pathways in the Mouse Trigeminal Ganglia and Nucleus 
      Accumbens.
PG  - 7929-7949
LID - 10.1007/s12035-019-01650-5 [doi]
AB  - The benefits of opioid-based treatments to mitigate chronic pain can be hindered 
      by the side effects of opioid-induced hyperalgesia (OIH) that can lead to higher 
      consumption and risk of addiction. The present study advances the understanding 
      of the molecular mechanisms associated with OIH by comparing mice presenting OIH 
      symptoms in response to chronic morphine exposure (OIH treatment) relative to 
      control mice (CON treatment). Using RNA-Seq profiles, gene networks were inferred 
      in the trigeminal ganglia (TG), a central nervous system region associated with 
      pain signaling, and in the nucleus accumbens (NAc), a region associated with 
      reward dependency. The biological process of nucleic acid processing was 
      over-represented among the 122 genes that exhibited a region-dependent treatment 
      effect. Within the 187 genes that exhibited a region-independent treatment 
      effect, circadian rhythm processes were enriched among the genes over-expressed 
      in OIH relative to CON mice. This enrichment was supported by the differential 
      expression of the period circadian clock 2 and 3 genes (Per2 and Per3). 
      Transcriptional regulators in the PAR bZip family that are influenced by the 
      circadian clock and that modulate neurotransmission associated with pain and drug 
      addiction were also over-expressed in OIH relative to CON mice. Also notable was 
      the under-expression in OIH relative to CON mice of the Toll-like receptor, 
      nuclear factor-kappa beta, and interferon gamma genes and enrichment of the 
      adaptive immune processes. The results from the present study offer insights to 
      advance the effective use of opioids for pain management while minimizing 
      hyperalgesia.
FAU - Zhang, Pan
AU  - Zhang P
AD  - Illinois Informatics Institute, University of Illinois at Urbana-Champaign, 
      Urbana, IL, USA.
FAU - Moye, Laura S
AU  - Moye LS
AD  - Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USA.
FAU - Southey, Bruce R
AU  - Southey BR
AD  - Department of Animal Sciences, University of Illinois at Urbana-Champaign, 
      Urbana, IL, USA.
FAU - Dripps, Isaac
AU  - Dripps I
AD  - Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USA.
FAU - Sweedler, Jonathan V
AU  - Sweedler JV
AD  - Department of Chemistry and the Beckman Institute, University of Illinois at 
      Urbana-Champaign, Urbana, IL, USA.
FAU - Pradhan, Amynah
AU  - Pradhan A
AD  - Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USA.
FAU - Rodriguez-Zas, Sandra L
AU  - Rodriguez-Zas SL
AUID- ORCID: 0000-0003-1122-4758
AD  - Department of Animal Sciences, University of Illinois at Urbana-Champaign, 
      Urbana, IL, USA. rodrgzzs@illinois.edu.
AD  - Department of Statistics, University of Illinois at Urbana-Champaign, Urbana, IL, 
      USA. rodrgzzs@illinois.edu.
LA  - eng
GR  - P30 DA018310/DA/NIDA NIH HHS/United States
GR  - ILLU-538-909/National Institute of Food and Agriculture/
GR  - MH096030/National Institutes of Mental Health/
GR  - MH096030/MH/NIMH NIH HHS/United States
GR  - K99 DA031243/DA/NIDA NIH HHS/United States
GR  - DA031243/DA/NIDA NIH HHS/United States
GR  - PR100085/U.S. Department of Defense/
GR  - 5P30DA018310 P30/DA/NIDA NIH HHS/United States
GR  - R21 MH096030/MH/NIMH NIH HHS/United States
GR  - R01 DA040688/DA/NIDA NIH HHS/United States
GR  - R00 DA031243/DA/NIDA NIH HHS/United States
PT  - Journal Article
DEP - 20190525
PL  - United States
TA  - Mol Neurobiol
JT  - Molecular neurobiology
JID - 8900963
RN  - 0 (Analgesics, Opioid)
SB  - IM
MH  - Adaptive Immunity/drug effects/*immunology
MH  - Analgesics, Opioid/*toxicity
MH  - Animals
MH  - Circadian Rhythm/drug effects/*immunology
MH  - Hyperalgesia/chemically induced/*immunology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Nucleus Accumbens/drug effects/*immunology
MH  - Pain Threshold/drug effects/physiology
MH  - Trigeminal Ganglion/drug effects/*immunology
PMC - PMC6842091
MID - NIHMS1530265
OTO - NOTNLM
OT  - Adaptive immune response
OT  - Circadian rhythm
OT  - Morphine
OT  - Opioid-induced hyperalgesia
OT  - RNA-Seq
COIS- Disclosure of potential conflicts of interest Conflict of Interest: The authors 
      declare that they have no conflict of interest.
EDAT- 2019/05/28 06:00
MHDA- 2020/04/09 06:00
PMCR- 2020/12/01
CRDT- 2019/05/27 06:00
PHST- 2019/02/21 00:00 [received]
PHST- 2019/05/13 00:00 [accepted]
PHST- 2019/05/28 06:00 [pubmed]
PHST- 2020/04/09 06:00 [medline]
PHST- 2019/05/27 06:00 [entrez]
PHST- 2020/12/01 00:00 [pmc-release]
AID - 10.1007/s12035-019-01650-5 [pii]
AID - 10.1007/s12035-019-01650-5 [doi]
PST - ppublish
SO  - Mol Neurobiol. 2019 Dec;56(12):7929-7949. doi: 10.1007/s12035-019-01650-5. Epub 
      2019 May 25.