Is the Neuroimmune System a Therapeutic Target for Opioid Use Disorder? A Systematic Review
Main Article Content
Abstract
Opioid use disorder (OUD) is an epidemic in the United States. In the past 12 months alone, there have been 75,000+ deaths attributed to opioid overdose: more than any other year in American history. Current pharmacotherapies for the treatment of OUD effectively suppress opioid withdrawal symptoms, but long-term relapse rates remain unacceptably high. Novel treatments for OUD are desperately needed to curb this epidemic. One target that has received considerable recent interest is the neuroimmune system. The neuroimmune system is anchored by glial cells, i.e., microglia and astrocytes, but neuroimmune signaling is known to influence neurons, including altering neurotransmission, synapse formation, and ultimately, brain function. Preclinical studies have shown that experimental attenuation of pro-inflammatory neuroimmune signaling modulates opioid addiction processes, including opioid reward, tolerance, and withdrawal symptoms, which suggests potential therapeutic benefit in patients. Whereas the peripheral immune system in OUD patients has been studied for decades and is well-understood, little is known about the neuroimmune system in OUD patients or its viability as a treatment target. Herein, we review the literature describing relationships between opioid administration and the neuroimmune system, the influence of neuroimmune signaling on opioid addiction processes, and the therapeutic potential for targeting the neuroimmune system in OUD subjects using glial modulator medications.
Keywords:
neuroinflammation, neuroimmune signaling, microglia, opioid use disorder, heroin, fentanyl
Article Details
How to Cite
TOLOFF, Katelyn; WOODCOCK, Eric A..
Is the Neuroimmune System a Therapeutic Target for Opioid Use Disorder? A Systematic Review.
Medical Research Archives, [S.l.], v. 10, n. 8, aug. 2022.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/2955>. Date accessed: 26 dec. 2024.
doi: https://doi.org/10.18103/mra.v10i8.2955.
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
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2. Dydyk AM, Jain NK, Gupta M. Opioid use disorder. StatPearls [Internet]. StatPearls Publishing; 2021.
3. American Psychiatric Association. 4th ed. Diagnostic and Statistical Manual of Mental Disorders. 1994.
4. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed. 2013.
5. Koob GF, Moal ML. Drug abuse: hedonic homeostatic dysregulation. Science. 1997;278(5335):52-58.
6. Koob GF, Volkow ND. Neurocircuitry of addiction. Neuropsychopharmacology. 2010;35(1):217-238.
7. Drug Overdose Deaths in the U.S. Top 100,000 Annually. November 17, 2021, 2021. https://www.cdc.gov/nchs/pressroom/nchs_press_releases/2021/20211117.htm
8. Brown R, Kraus C, Fleming M, Reddy S. Methadone: applied pharmacology and use as adjunctive treatment in chronic pain. Postgraduate medical journal. 2004;80(949):654-659.
9. Marteau D, McDonald R, Patel K. The relative risk of fatal poisoning by methadone or buprenorphine within the wider population of England and Wales. BMJ open. 2015;5(5):e007629.
10. Gudin J, Fudin J. A narrative pharmacological review of buprenorphine: a unique opioid for the treatment of chronic pain. Pain and Therapy. 2020;9(1):41-54.
11. Volpe DA, Tobin GAM, Mellon RD, et al. Uniform assessment and ranking of opioid mu receptor binding constants for selected opioid drugs. Regulatory Toxicology and Pharmacology. 2011;59(3):385-390.
12. Lutfy K, Cowan A. Buprenorphine: a unique drug with complex pharmacology. Current neuropharmacology. 2004;2(4):395-402.
13. Strain EC, Walsh SL, Bigelow GE. Blockade of hydromorphone effects by buprenorphine/naloxone and buprenorphine. Psychopharmacology. 2002;159(2):161-166.
14. Singh D, Saadabadi A. Naltrexone. 2018;
15. Bell J, Strang J. Medication treatment of opioid use disorder. Biological psychiatry. 2020;87(1):82-88.
16. Mattick RP, Breen C, Kimber J, Davoli M. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane database of systematic reviews. 2014;(2)
17. Hser YI, Saxon AJ, Huang D, et al. Treatment retention among patients randomized to buprenorphine/naloxone compared to methadone in a multi‐site trial. Addiction. 2014;109(1):79-87.
18. Hser YI, Evans E, Huang D, et al. Long‐term outcomes after randomization to buprenorphine/naloxone versus methadone in a multi‐site trial. Addiction. 2016;111(4):695-705.
19. Volkow N, Collins F. All scientific hands on deck” to end the opioid crisis. Web blog comment] Retrieved from: https://www drugabuse gov/about-nida/noras-blog/2017/05/all-scientific-hands-deck-to-end-opioid-crisis. 2017;
20. Volkow N, Czernin J. A Conversation Between Nora Volkow and Johannes Czernin. Journal of Nuclear Medicine. 2019;60(6):717-720.
21. Jacobsen JHW, Watkins LR, Hutchinson MR. Discovery of a novel site of opioid action at the innate immune pattern-recognition receptor TLR4 and its role in addiction. International review of neurobiology. 2014;118:129-163.
22. Saijo K, Glass CK. Microglial cell origin and phenotypes in health and disease. Nature Reviews Immunology. 2011;11(11):775-787.
23. Ransohoff RM. How neuroinflammation contributes to neurodegeneration. Science. 2016;353(6301):777-783.
24. Subhramanyam CS, Wang C, Hu Q, Dheen ST. Microglia-mediated neuroinflammation in neurodegenerative diseases. Elsevier; 2019:112-120.
25. Kwon HS, Koh S-H. Neuroinflammation in neurodegenerative disorders: the roles of microglia and astrocytes. Translational neurodegeneration. 2020;9(1):1-12.
26. Hickman SE, Kingery ND, Ohsumi TK, et al. The microglial sensome revealed by direct RNA sequencing. Nature neuroscience. 2013;16(12):1896-1905.
27. Glass CK, Saijo K, Winner B, Marchetto MC, Gage FH. Mechanisms underlying inflammation in neurodegeneration. Cell. 2010;140(6):918-934.
28. Hickman S, Izzy S, Sen P, Morsett L, El Khoury J. Microglia in neurodegeneration. Nature neuroscience. 2018;21(10):1359-1369.
29. Ransohoff RM, Brown MA. Innate immunity in the central nervous system. The Journal of clinical investigation. 2012;122(4):1164-1171.
30. Hutchinson MR, Bland ST, Johnson KW, Rice KC, Maier SF, Watkins LR. Opioid-induced glial activation: mechanisms of activation and implications for opioid analgesia, dependence, and reward. TheScientificWorldJournal. 2007;7:98-111.
31. Abdelhak A, Hottenrott T, Morenas-Rodríguez E, et al. Glial activation markers in CSF and serum from patients with primary progressive multiple sclerosis: potential of serum GFAP as disease severity marker? Frontiers in neurology. 2019;10:280.
32. Mika J. -Modulation of microglia can attenuate neuropathic pain symptoms and enhance morphine effectiveness. Pharmacological reports. 2008;60(3):297.
33. Boulanger LM. Immune proteins in brain development and synaptic plasticity. Neuron. 2009;64(1):93-109.
34. Deverman BE, Patterson PH. Cytokines and CNS development. Neuron. 2009;64(1):61-78.
35. Frank MG, Watkins LR, Maier SF. Stress-and glucocorticoid-induced priming of neuroinflammatory responses: potential mechanisms of stress-induced vulnerability to drugs of abuse. Brain, behavior, and immunity. 2011;25:S21-S28.
36. Haroon E, Raison CL, Miller AH. Psychoneuroimmunology meets neuropsychopharmacology: translational implications of the impact of inflammation on behavior. Neuropsychopharmacology. 2012;37(1):137-162.
37. Hueston CM, Deak T. The inflamed axis: the interaction between stress, hormones, and the expression of inflammatory-related genes within key structures comprising the hypothalamic–pituitary–adrenal axis. Physiology & behavior. 2014;124:77-91.
38. Besedovsky H, Del Rey A. The cytokine-HPA axis feed-back circuit. Zeitschrift für Rheumatologie. 2000;59(2):II26-II30.
39. Yirmiya R, Goshen I. Immune modulation of learning, memory, neural plasticity and neurogenesis. Brain, behavior, and immunity. 2011;25(2):181-213.
40. Kohman RA, Rhodes JS. Neurogenesis, inflammation and behavior. Brain, behavior, and immunity. 2013;27:22-32.
41. Cohen O, Reichenberg A, Perry C, et al. Endotoxin-induced changes in human working and declarative memory associate with cleavage of plasma “readthrough” acetylcholinesterase. Journal of Molecular Neuroscience. 2003;21(3):199-212.
42. Reichenberg A, Yirmiya R, Schuld A, et al. Cytokine-associated emotional and cognitive disturbances in humans. Archives of general psychiatry. 2001;58(5):445-452.
43. Notter T, Coughlin JM, Sawa A, Meyer U. Reconceptualization of translocator protein as a biomarker of neuroinflammation in psychiatry. Molecular psychiatry. 2018;23(1):36-47.
44. Coller JK, Hutchinson MR. Implications of central immune signaling caused by drugs of abuse: mechanisms, mediators and new therapeutic approaches for prediction and treatment of drug dependence. Pharmacology & therapeutics. 2012;134(2):219-245.
45. Linker K, Cross S, Leslie F. Glial mechanisms underlying substance use disorders. European Journal of Neuroscience. 2019;50(3):2574-2589.
46. Hutchinson MR, Lewis SS, Coats BD, et al. Reduction of opioid withdrawal and potentiation of acute opioid analgesia by systemic AV411 (ibudilast). Brain, behavior, and immunity. 2009;23(2):240-250.
47. Watkins LR, Hutchinson MR, Milligan ED, Maier SF. “Listening” and “talking” to neurons: implications of immune activation for pain control and increasing the efficacy of opioids. Brain research reviews. 2007;56(1):148-169.
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