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Article

Alternative Splicing Mechanisms Underlying Opioid-Induced Hyperalgesia

1
Illinois Informatics Institute, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
2
Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
3
Department of Chemistry and the Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
4
Department of Psychiatry, University of Illinois at Chicago, Chicago, IL 60612, USA
5
Department of Statistics, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Isabelle Schrauwen
Genes 2021, 12(10), 1570; https://doi.org/10.3390/genes12101570
Received: 24 August 2021 / Revised: 19 September 2021 / Accepted: 30 September 2021 / Published: 1 October 2021
(This article belongs to the Special Issue Genetic Basis of Sensory and Neurological Disorders)
Prolonged use of opioids can cause opioid-induced hyperalgesia (OIH). The impact of alternative splicing on OIH remains partially characterized. A study of the absolute and relative modes of action of alternative splicing further the understanding of the molecular mechanisms underlying OIH. Differential absolute and relative isoform profiles were detected in the trigeminal ganglia and nucleus accumbens of mice presenting OIH behaviors elicited by chronic morphine administration relative to control mice. Genes that participate in glutamatergic synapse (e.g., Grip1, Grin1, Wnk3), myelin protein processes (e.g., Mbp, Mpz), and axon guidance presented absolute and relative splicing associated with OIH. Splicing of genes in the gonadotropin-releasing hormone receptor pathway was detected in the nucleus accumbens while splicing in the vascular endothelial growth factor, endogenous cannabinoid signaling, circadian clock system, and metabotropic glutamate receptor pathways was detected in the trigeminal ganglia. A notable finding was the prevalence of alternatively spliced transcription factors and regulators (e.g., Ciart, Ablim2, Pbx1, Arntl2) in the trigeminal ganglia. Insights into the nociceptive and antinociceptive modulatory action of Hnrnpk were gained. The results from our study highlight the impact of alternative splicing and transcriptional regulators on OIH and expose the need for isoform-level research to advance the understanding of morphine-associated hyperalgesia. View Full-Text
Keywords: morphine; transcript isoform; glutamatergic system; transcription factor morphine; transcript isoform; glutamatergic system; transcription factor
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MDPI and ACS Style

Zhang, P.; Perez, O.C.; Southey, B.R.; Sweedler, J.V.; Pradhan, A.A.; Rodriguez-Zas, S.L. Alternative Splicing Mechanisms Underlying Opioid-Induced Hyperalgesia. Genes 2021, 12, 1570. https://doi.org/10.3390/genes12101570

AMA Style

Zhang P, Perez OC, Southey BR, Sweedler JV, Pradhan AA, Rodriguez-Zas SL. Alternative Splicing Mechanisms Underlying Opioid-Induced Hyperalgesia. Genes. 2021; 12(10):1570. https://doi.org/10.3390/genes12101570

Chicago/Turabian Style

Zhang, Pan, Olivia C. Perez, Bruce R. Southey, Jonathan V. Sweedler, Amynah A. Pradhan, and Sandra L. Rodriguez-Zas. 2021. "Alternative Splicing Mechanisms Underlying Opioid-Induced Hyperalgesia" Genes 12, no. 10: 1570. https://doi.org/10.3390/genes12101570

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