Targeting the TRPV1 pain pathway in osteoarthritis of the knee
Mobasheri, Ali; Rannou, François; Ivanavicius, Stefan; Conaghan, Philip G. (2024-10-25)
Taylor & Francis
25.10.2024
Mobasheri, A., Rannou, F., Ivanavicius, S., & Conaghan, P. G. (2024). Targeting the TRPV1 pain pathway in osteoarthritis of the knee. Expert Opinion on Therapeutic Targets, 28(10), 843–856. https://doi.org/10.1080/14728222.2024.2416961
https://creativecommons.org/licenses/by-nc-nd/4.0/
© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.
https://creativecommons.org/licenses/by-nc-nd/4.0/
© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.
https://creativecommons.org/licenses/by-nc-nd/4.0/
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:oulu-202410296502
https://urn.fi/URN:NBN:fi:oulu-202410296502
Tiivistelmä
Abstract
Introduction:
The growing prevalence and lack of effective pain therapies for knee osteoarthritis (KOA) results in a substantial unmet need for novel analgesic therapies. The transient receptor potential vanilloid 1 (TRPV1) receptor is expressed in subsets of nociceptive sensory neurons and has major roles in pain transmission and regulation. In the structures of the knee joint, nociceptors are present in abundance.
Areas covered:
TRPV1-expressing nociceptors in the knee represent a rational target to modulate activity at the origin of the pain pathway in KOA and may avoid systemic side effects seen with currently available analgesics. TRPV1 antagonists can induce analgesia, but hyperthermia and thermal hypesthesia side effects have limited their utility. Clinical development of TRPV1 agonists for pain management has progressed further than that of TRPV1 antagonists. Capsaicin and resiniferatoxin have provided proof-of-concept for the modulation of TRPV1 activity in KOA.
Expert opinion:
Intra-articular administration of TRPV1 agonists enables direct delivery to target nerve terminals in the knee, offering a potentially transformative approach for the management of pain associated with KOA. Here, we explore the advances in understanding innervation of the knee joint in KOA, the role of TRPV1-expressing neurons and progress in developing TRPV1 modulators for KOA.
Introduction:
The growing prevalence and lack of effective pain therapies for knee osteoarthritis (KOA) results in a substantial unmet need for novel analgesic therapies. The transient receptor potential vanilloid 1 (TRPV1) receptor is expressed in subsets of nociceptive sensory neurons and has major roles in pain transmission and regulation. In the structures of the knee joint, nociceptors are present in abundance.
Areas covered:
TRPV1-expressing nociceptors in the knee represent a rational target to modulate activity at the origin of the pain pathway in KOA and may avoid systemic side effects seen with currently available analgesics. TRPV1 antagonists can induce analgesia, but hyperthermia and thermal hypesthesia side effects have limited their utility. Clinical development of TRPV1 agonists for pain management has progressed further than that of TRPV1 antagonists. Capsaicin and resiniferatoxin have provided proof-of-concept for the modulation of TRPV1 activity in KOA.
Expert opinion:
Intra-articular administration of TRPV1 agonists enables direct delivery to target nerve terminals in the knee, offering a potentially transformative approach for the management of pain associated with KOA. Here, we explore the advances in understanding innervation of the knee joint in KOA, the role of TRPV1-expressing neurons and progress in developing TRPV1 modulators for KOA.
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