Tags

Type your tag names separated by a space and hit enter

Thrombin receptor: An endogenous inhibitor of inflammatory pain, activating opioid pathways.
Pain. 2009 Nov; 146(1-2):121-9.PAIN

Abstract

Serine proteases such as thrombin, trypsin and mast cell tryptase can act on different cell types through protease-activated receptors (PARs). These receptors have been shown to be implicated in several phenomena such as inflammation, platelet activation, immune response and atherosclerosis. Several studies recently reported PARs expression on neurons and some of them demonstrated that these receptors could interfere with nociception. The contribution of PAR(1) to inflammatory pain and the mechanism involved in this phenomenon were investigated. Intraplantar injection of PAR(1) agonist increased withdrawal latency and reduced response frequency to von Frey filaments, thus inhibiting nociceptive response to both mechanical and thermal stimuli in mice. PAR(1) agonist also reduced carrageenan-induced inflammatory hyperalgesia. The anti-nociceptive effects of PAR(1) agonist were mediated by endogenous opioids, as this effect was inhibited by local injection of naloxone methiodide, and because intraplantar injection of PAR(1) agonist increased mRNA expression of the endogenous opioid precursor proenkephalin. However, PAR(1) agonist was not able to inhibit calcium signals in isolated sensory neurons exposed to pro-nociceptive agents. Finally, despite similar inflammatory parameters, PAR(1)-deficient mice showed a strong potentiation of inflammatory hyperalgesia induced by the intraplantar injection of either formalin or carrageenan, or in the chronic model of collagen-induced arthritis, compared to wild-type mice. This study highlights a previously unknown endogenous mechanism of analgesia, showing a central role for the thrombin receptor PAR(1) in the regulation of inflammatory pain and as an activator of opioid pathways.

Authors+Show Affiliations

INSERM, U563, Centre de Physiopathologie de Toulouse Purpan, F-31000 Toulouse, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19674841

Citation

Martin, Laurence, et al. "Thrombin Receptor: an Endogenous Inhibitor of Inflammatory Pain, Activating Opioid Pathways." Pain, vol. 146, no. 1-2, 2009, pp. 121-9.
Martin L, Augé C, Boué J, et al. Thrombin receptor: An endogenous inhibitor of inflammatory pain, activating opioid pathways. Pain. 2009;146(1-2):121-9.
Martin, L., Augé, C., Boué, J., Buresi, M. C., Chapman, K., Asfaha, S., Andrade-Gordon, P., Steinhoff, M., Cenac, N., Dietrich, G., & Vergnolle, N. (2009). Thrombin receptor: An endogenous inhibitor of inflammatory pain, activating opioid pathways. Pain, 146(1-2), 121-9. https://doi.org/10.1016/j.pain.2009.07.016
Martin L, et al. Thrombin Receptor: an Endogenous Inhibitor of Inflammatory Pain, Activating Opioid Pathways. Pain. 2009;146(1-2):121-9. PubMed PMID: 19674841.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Thrombin receptor: An endogenous inhibitor of inflammatory pain, activating opioid pathways. AU - Martin,Laurence, AU - Augé,Céline, AU - Boué,Jérôme, AU - Buresi,Michelle C, AU - Chapman,Kevin, AU - Asfaha,Samuel, AU - Andrade-Gordon,Patricia, AU - Steinhoff,Martin, AU - Cenac,Nicolas, AU - Dietrich,Gilles, AU - Vergnolle,Nathalie, Y1 - 2009/08/11/ PY - 2008/12/10/received PY - 2009/07/08/revised PY - 2009/07/13/accepted PY - 2009/8/14/entrez PY - 2009/8/14/pubmed PY - 2009/12/31/medline SP - 121 EP - 9 JF - Pain JO - Pain VL - 146 IS - 1-2 N2 - Serine proteases such as thrombin, trypsin and mast cell tryptase can act on different cell types through protease-activated receptors (PARs). These receptors have been shown to be implicated in several phenomena such as inflammation, platelet activation, immune response and atherosclerosis. Several studies recently reported PARs expression on neurons and some of them demonstrated that these receptors could interfere with nociception. The contribution of PAR(1) to inflammatory pain and the mechanism involved in this phenomenon were investigated. Intraplantar injection of PAR(1) agonist increased withdrawal latency and reduced response frequency to von Frey filaments, thus inhibiting nociceptive response to both mechanical and thermal stimuli in mice. PAR(1) agonist also reduced carrageenan-induced inflammatory hyperalgesia. The anti-nociceptive effects of PAR(1) agonist were mediated by endogenous opioids, as this effect was inhibited by local injection of naloxone methiodide, and because intraplantar injection of PAR(1) agonist increased mRNA expression of the endogenous opioid precursor proenkephalin. However, PAR(1) agonist was not able to inhibit calcium signals in isolated sensory neurons exposed to pro-nociceptive agents. Finally, despite similar inflammatory parameters, PAR(1)-deficient mice showed a strong potentiation of inflammatory hyperalgesia induced by the intraplantar injection of either formalin or carrageenan, or in the chronic model of collagen-induced arthritis, compared to wild-type mice. This study highlights a previously unknown endogenous mechanism of analgesia, showing a central role for the thrombin receptor PAR(1) in the regulation of inflammatory pain and as an activator of opioid pathways. SN - 1872-6623 UR - https://www.unboundmedicine.com/medline/citation/19674841/Thrombin_receptor:_An_endogenous_inhibitor_of_inflammatory_pain_activating_opioid_pathways_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3959(09)00401-1 DB - PRIME DP - Unbound Medicine ER -