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

Autor: Susanna Fürst, Zoltán S. Zádori, Ferenc Zádor, Kornél Király, Mihály Balogh, Szilvia B. László, Barbara Hutka, Amir Mohammadzadeh, Chiara Calabrese, Anna Rita Galambos, Pál Riba, Patrizia Romualdi, Sándor Benyhe, Júlia Timár, Helmut Schmidhammer, Mariana Spetea, Mahmoud Al-Khrasani
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Molecules, Vol 25, Iss 11, p 2473 (2020)
Druh dokumentu: article
ISSN: 25112473
1420-3049
DOI: 10.3390/molecules25112473
Popis: There is growing evidence on the role of peripheral µ-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, β-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.
Databáze: Directory of Open Access Journals
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