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The Role of 5-HT2a/2c Receptors in Nociception and Opioid Antinociception: a Review of the Preclinical Literature

  • Substance Use Disorders (FG Moeller, Section Editor)
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Opinion Statement

Opioid analgesics are one of the most commonly prescribed drugs for the treatment of pain, but there are many potentially harmful side effects with their prolonged use. In light of the escalating opioid epidemic, there is a drive to search for novel analgesics or potential combination therapies that may reduce the incidence of side effects. Serotonergic compounds are used in the clinic for the treatment of chronic pain. Of these compounds, ligands that act at the 5-HT2a and 5-HT2c receptors may be clinically useful as adjunctive therapies to opioids. The purpose of this review is to describe the preclinical evidence supporting the role of these receptors in pain states and how these receptors interact with opioid analgesics. 5-HT2a receptor antagonists have shown efficacy in the reducing nocifensive, or pain-like withdrawal behaviors or responses, associated with neuropathy and inflammation. In addition, the 5-HT2a receptor may interact on a cellular level with the mu opioid receptor. 5-HT2c agonists are reported to act as antinociceptive agents when administered directly into the spinal cord. 5-HT2c agonists also attenuate behavioral symptoms of opioid dependence, though nothing is known about their interactions with opioid analgesics. In conclusion, although the preclinical literature poses a potentially interesting role for the 5-HT2a/2c receptors in nociception, their interaction with the MOR is unclear and needs further preclinical evaluation.

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  1. Department of Pharmacology and Toxicology, Virginia Commonwealth University, 1112 East Clay Street, McGuire Hall, Room 100, P.O. Box 980613, Richmond, VA, 23298-0613, USA

    Kumiko Lippold B.S & William Dewey Ph.D.

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  1. Kumiko Lippold B.S
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Correspondence to Kumiko Lippold B.S.

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Lippold, K., Dewey, W. The Role of 5-HT2a/2c Receptors in Nociception and Opioid Antinociception: a Review of the Preclinical Literature. Curr Treat Options Psych 4, 210–220 (2017). https://doi.org/10.1007/s40501-017-0111-3

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