On the Role of Peripheral Sensory and Gut Mu Opioid Receptors: Peripheral Analgesia and Tolerance

Susanna Furst*, Zoltan S. Zadori, Ferenc Zador, Kornel Kiraly, Mihaly Balogh, Szilvia B. Laszlo, Barbara Hutka, Amir Mohammadzadeh, Chiara Calabrese, Anna Rita Galambos, Pal Riba, Patrizia Romualdi, Sandor Benyhe, Julia Timar, Helmut Schmidhammer, Mariana Spetea, Mahmoud Al-Khrasani

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

13 Citations (Scopus)

Abstract

There is growing evidence on the role of peripheral mu-opioid receptors (MORs) in analgesia and analgesic tolerance. Opioid analgesics are the mainstay in the management of moderate to severe pain, and their efficacy in the alleviation of pain is well recognized. Unfortunately, chronic treatment with opioid analgesics induces central analgesic tolerance, thus limiting their clinical usefulness. Numerous molecular mechanisms, including receptor desensitization, G-protein decoupling, beta-arrestin recruitment, and alterations in the expression of peripheral MORs and microbiota have been postulated to contribute to the development of opioid analgesic tolerance. However, these studies are largely focused on central opioid analgesia and tolerance. Accumulated literature supports that peripheral MORs mediate analgesia, but controversial results on the development of peripheral opioid receptors-mediated analgesic tolerance are reported. In this review, we offer evidence on the consequence of the activation of peripheral MORs in analgesia and analgesic tolerance, as well as approaches that enhance analgesic efficacy and decrease the development of tolerance to opioids at the peripheral sites. We have also addressed the advantages and drawbacks of the activation of peripheral MORs on the sensory neurons and gut (leading to dysbiosis) on the development of central and peripheral analgesic tolerance.

Original languageEnglish
Article number2473
Number of pages22
JournalMolecules
Volume25
Issue number11
DOIs
Publication statusPublished - Jun-2020
Externally publishedYes

Keywords

  • peripheral mu-opioid receptors
  • analgesia
  • peripheral analgesic tolerance
  • dysbiosis
  • NEUROPATHIC PAIN
  • MORPHINE-TOLERANCE
  • SYSTEMIC MORPHINE
  • MOLECULAR-MECHANISMS
  • FUNCTIONAL EXPRESSION
  • INDUCED HYPERALGESIA
  • GLUTAMATE RECEPTORS
  • OPIATE RECEPTOR
  • UNITED-STATES
  • SPINAL-CORD

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