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Role of TRPV1 in nociception and edema induced by monosodium urate crystals in rats.
Pain. 2011 Aug; 152(8):1777-1788.PAIN

Abstract

Gout is characterized by the deposition of monosodium urate (MSU) crystals. Despite being one of the most painful forms of arthritis, gout and the mechanisms responsible for its acute attacks are poorly understood. In the present study, we found that MSU caused dose-related nociception (ED(50) [ie, the necessary dose of MSU to elicit 50% of the response relative to the control value]=0.04 [95% confidence interval 0.01-0.11]mg/paw) and edema (ED(50)=0.08 [95% confidence interval 0.04-0.16]mg/paw) when injected into the hind paw of rats. Treatment with the selective TRPV1 receptor (also known as capsaicin receptor and vanilloid receptor-1) antagonists SB366791 or AMG9810 largely prevented nociceptive and edematogenic responses to MSU. Moreover, the desensitization of capsaicin-sensitive afferent fibers as well as pretreatment with the tachykinin NK(1) receptor antagonist RP 67580 also significantly prevented MSU-induced nociception and edema. Once MSU was found to induce mast cell stimulation, we investigated the participation of these cells on MSU effects. Prior degranulation of mast cells by repeated treatment with the compound 48/80 decreased MSU-induced nociception and edema or histamine and serotonin levels in the injected tissue. Moreover, pretreatment with the mast cell membrane stabilizer cromolyn effectively prevented nociceptive and edematogenic responses to MSU. MSU induced a release of histamine, serotonin, and tryptase in the injected tissue, confirming mast cell degranulation. Furthermore, the antagonism of histaminergic H1 and serotoninergic receptors decreased the edema, but not the nociception of MSU. Finally, the prevention of the tryptase activity was capable of largely reducing both MSU-induced nociception and edema. Collectively, the present findings demonstrate that MSU produces nociceptive and edematogenic responses mediated by TRPV1 receptor activation and mast cell degranulation.

Authors+Show Affiliations

Programa de Pós-graduação em Farmacologia, Centro de Ciências da Saúde, Universidade Federal de Santa Maria, RS, Brazil Departmento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, RS, Brazil Programa de Pós-graduação em Ciências Biológicas, Bioquímica Toxicológica, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, RS, Brazil Programa de Pós-graduação em Farmacologia Bioquímica e Molecular, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.No 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

21550723

Citation

Hoffmeister, Carin, et al. "Role of TRPV1 in Nociception and Edema Induced By Monosodium Urate Crystals in Rats." Pain, vol. 152, no. 8, 2011, pp. 1777-1788.
Hoffmeister C, Trevisan G, Rossato MF, et al. Role of TRPV1 in nociception and edema induced by monosodium urate crystals in rats. Pain. 2011;152(8):1777-1788.
Hoffmeister, C., Trevisan, G., Rossato, M. F., de Oliveira, S. M., Gomez, M. V., & Ferreira, J. (2011). Role of TRPV1 in nociception and edema induced by monosodium urate crystals in rats. Pain, 152(8), 1777-1788. https://doi.org/10.1016/j.pain.2011.03.025
Hoffmeister C, et al. Role of TRPV1 in Nociception and Edema Induced By Monosodium Urate Crystals in Rats. Pain. 2011;152(8):1777-1788. PubMed PMID: 21550723.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of TRPV1 in nociception and edema induced by monosodium urate crystals in rats. AU - Hoffmeister,Carin, AU - Trevisan,Gabriela, AU - Rossato,Mateus Fortes, AU - de Oliveira,Sara Marchesan, AU - Gomez,Marcus Vinícius, AU - Ferreira,Juliano, Y1 - 2011/05/07/ PY - 2009/12/15/received PY - 2011/02/25/revised PY - 2011/03/21/accepted PY - 2011/5/10/entrez PY - 2011/5/10/pubmed PY - 2011/12/13/medline SP - 1777 EP - 1788 JF - Pain JO - Pain VL - 152 IS - 8 N2 - Gout is characterized by the deposition of monosodium urate (MSU) crystals. Despite being one of the most painful forms of arthritis, gout and the mechanisms responsible for its acute attacks are poorly understood. In the present study, we found that MSU caused dose-related nociception (ED(50) [ie, the necessary dose of MSU to elicit 50% of the response relative to the control value]=0.04 [95% confidence interval 0.01-0.11]mg/paw) and edema (ED(50)=0.08 [95% confidence interval 0.04-0.16]mg/paw) when injected into the hind paw of rats. Treatment with the selective TRPV1 receptor (also known as capsaicin receptor and vanilloid receptor-1) antagonists SB366791 or AMG9810 largely prevented nociceptive and edematogenic responses to MSU. Moreover, the desensitization of capsaicin-sensitive afferent fibers as well as pretreatment with the tachykinin NK(1) receptor antagonist RP 67580 also significantly prevented MSU-induced nociception and edema. Once MSU was found to induce mast cell stimulation, we investigated the participation of these cells on MSU effects. Prior degranulation of mast cells by repeated treatment with the compound 48/80 decreased MSU-induced nociception and edema or histamine and serotonin levels in the injected tissue. Moreover, pretreatment with the mast cell membrane stabilizer cromolyn effectively prevented nociceptive and edematogenic responses to MSU. MSU induced a release of histamine, serotonin, and tryptase in the injected tissue, confirming mast cell degranulation. Furthermore, the antagonism of histaminergic H1 and serotoninergic receptors decreased the edema, but not the nociception of MSU. Finally, the prevention of the tryptase activity was capable of largely reducing both MSU-induced nociception and edema. Collectively, the present findings demonstrate that MSU produces nociceptive and edematogenic responses mediated by TRPV1 receptor activation and mast cell degranulation. SN - 1872-6623 UR - https://www.unboundmedicine.com/medline/citation/21550723/Role_of_TRPV1_in_nociception_and_edema_induced_by_monosodium_urate_crystals_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/00006396-201108000-00017 DB - PRIME DP - Unbound Medicine ER -