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Opioid Effects on the Central Nervous System and the Peripheral Immune System: Implications for Opioid Tolerance

  • Pharmacometrics and Quantitative System Pharmacology (S Woo, Section Editor)
  • Published:
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Abstract

Purpose of Review

Opioids exert differential effects in the central nervous system (CNS) and the peripheral immune system. Both systems may play a role in the development of opioid tolerance. This review provides a brief overview of the opioid effects on the CNS and peripheral immune system and discusses the potential roles of the connections between the two systems in opioid tolerance.

Recent Findings

Opioids induced pro-inflammatory response of the CNS immune cells through several mechanisms that involve mu-opioid receptor and Toll-like receptor 4. This neuroinflammation leads to enhanced neuron excitability and opioid tolerance and/or hyperalgesia. Opioid-exposed neuronal cells also contributed to CNS stress and inflammatory responses, further resulted in neuroinflammation. On the contrary, most studies have shown that opioids exert immunosuppressive effects in the peripheral immune system. There are, however, some evidence suggested that opioids may induce dose-, time-, and opioid agent-dependent pro-inflammatory responses. Though opioids have the opposite effects in the CNS and the peripheral immune system, newer evidence have suggested that the peripheral immune system plays a significant role in neuroinflammation and opioid tolerance.

Summary

Opioid effects on the CNS and the peripheral immune system have been studied extensively; however, the integrated effects of opioids on tolerance development are yet to be explored. Further understanding of the integrated/interactive effects of opioids on peripheral immune cells and the CNS is required so that their interactions may be exploited for the identification of new therapeutics and biomarkers.

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  1. Pharmacy Practice Division, University of Wisconsin-Madison School of Pharmacy, 1033 Rennebohm Hall, 777 Highland Ave, Madison, WI, 53705, USA

    Sin Yin Lim

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Topical Collection on Pharmacometrics and Quantitative System Pharmacology

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Lim, S.Y. Opioid Effects on the Central Nervous System and the Peripheral Immune System: Implications for Opioid Tolerance. Curr Pharmacol Rep 7, 81–95 (2021). https://doi.org/10.1007/s40495-021-00258-5

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