DESCRIPTION:

Molecular mechanisms associated with opioid-induced hyperalgesia (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. Mice in the OIH treatment group were injected with morphine dissolved in 0.9% saline solution whereas mice in the CON treatment group were injected with saline vehicle administered as a 10mL/kg volume. Extended list of genes differentially expressed (FDR-adjusted P-value < 0.1) between opioid-induced hyperalgesia (OIH) and control (CON) mice.

LABEL:

Morphine_hyperalgesia_C57B1/6J_qvalue

SCORE TYPE:

Q-Value

DATE ADDED:

2024-01-03

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

Pan Zhang, Laura S Moye, Bruce R Southey, Isaac Dripps, Jonathan V Sweedler, Amynah Pradhan, Sandra L Rodriguez-Zas

TITLE:

Opioid-Induced Hyperalgesia Is Associated with Dysregulation of Circadian Rhythm and Adaptive Immune Pathways in the Mouse Trigeminal Ganglia and Nucleus Accumbens.

JOURNAL:

Molecular neurobiology Dec 2019, Vol 56, pp. 7929-7949

ABSTRACT:

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. PUBMED: 31129808
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