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Recent Advances in Peripheral Opioid Receptor Therapeutics

  • Alternative Treatments for Pain Medicine (M Jones, Section Editor)
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Abstract

Purpose of Review

Although opioids are excellent analgesics, they are associated with severe short- and long-term side effects that are especially concerning for the treatment of chronic pain. Peripherally acting opioid receptor agonists promise to mitigate the more serious centrally mediated side effects of opioids, and the goal of this paper is to identify and elaborate on recent advances in these peripheral opioid receptor therapeutics.

Recent Findings

Peripheral opioid receptor agonists are effective analgesics that at the same time circumvent the problem of centrally mediated opioid side effects by (1) preferentially targeting peripheral opioid receptors that are often the source of the pain and (2) their markedly diminished permeability or activity across the blood-brain barrier. Recent novel bottom-up approaches have been notable for the design of therapeutics that are either active only at inflamed tissue, as in the case of fentanyl-derived pH-sensitive opioid ligands, or too bulky or hydrophilic to cross the blood-brain barrier, as in the case of morphine covalently bound to hyperbranched polyglycerols.

Summary

Recent innovations in peripheral opioid receptor therapeutics of pH-sensitive opioid ligands and limiting opioid permeability across the blood-brain barrier have had promising results in animal models. While this is grounds for optimism that some of these therapeutics will be efficacious in human subjects at a future date, each drug must undergo individualized testing for specific chronic pain syndromes to establish not only the nuances of each drug’s therapeutic effect but also a comprehensive safety profile.

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Authors and Affiliations

  1. Department of Anesthesia, Critical Care, and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA, 02215, USA

    Raghav Seth & Sumanth S. Kuppalli

  2. Department of Anesthesiology, New York-Presbyterian/Weill Cornell Medicine, New York, NY, USA

    Danielle Nadav

  3. Department of Anesthesiology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Grant Chen & Amitabh Gulati

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  1. Raghav Seth
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Correspondence to Raghav Seth.

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Seth, R., Kuppalli, S.S., Nadav, D. et al. Recent Advances in Peripheral Opioid Receptor Therapeutics. Curr Pain Headache Rep 25, 46 (2021). https://doi.org/10.1007/s11916-021-00951-6

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