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P2X3 receptors induced inflammatory nociception modulated by TRPA1, 5-HT3 and 5-HT1A receptors.
Pharmacol Biochem Behav. 2013 Nov; 112:49-55.PB

Abstract

It has been described that endogenous ATP via activation of P2X3 and P2X2/3 receptors contributes to inflammatory nociception in different models, including the formalin injected in subcutaneous tissue of the rat's hind paw. In this study, we have evaluated whether TRPA1, 5-HT3 and 5-HT1A receptors, whose activation is essential to formalin-induced inflammatory nociception, are involved in the nociception induced by activation of P2X3 receptors on subcutaneous tissue of the rat's hind paw. We have also evaluated whether the activation of P2X3 receptors increases the susceptibility of primary afferent neurons to formalin action modulated by activation of TRPA1, 5-HT3 or 5-HT1A receptors. Nociceptive response intensity was measured by observing the rat's behavior and considering the number of times the animal reflexively raised its hind paw (flinches) in 60min. Local subcutaneous administration of the selective TRPA1, 5-HT3 or 5-HT1A receptor antagonists HC 030031, tropisetron and WAY 100,135, respectively, prevented the nociceptive responses induced by the administration in the same site of the non-selective P2X3 receptor agonist αβmeATP. Administration of the selective P2X3 and P2X2/3 receptor antagonist A-317491 or pretreatment with oligonucleotides antisense against P2X3 receptor prevented the formalin-induced behavioral nociceptive responses during the first and second phases. Also, the co-administration of a subthreshold dose of αβmeATP with a subthreshold dose of formalin induced nociceptive behavior, which was prevented by local administration of tropisetron, HC 030031 or WAY 100, 135. These findings have demonstrated that the activation of P2X3 receptors induces inflammatory nociception modulated by TRPA1, 5-HT3 and 5-HT1A receptors. Also, they suggest that inflammatory nociception is modulated by the release of endogenous ATP and P2X3 receptor activation, which in turn, increases primary afferent nociceptor susceptibility to the action of inflammatory mediators via interaction with TRPA1, 5-HT3 and 5-HT1A receptors in the peripheral tissue.

Authors+Show Affiliations

Department of Structural and Functional Biology, Institute of Biology, State University of Campinas - UNICAMP, 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

24120766

Citation

Krimon, Suzy, et al. "P2X3 Receptors Induced Inflammatory Nociception Modulated By TRPA1, 5-HT3 and 5-HT1A Receptors." Pharmacology, Biochemistry, and Behavior, vol. 112, 2013, pp. 49-55.
Krimon S, Araldi D, do Prado FC, et al. P2X3 receptors induced inflammatory nociception modulated by TRPA1, 5-HT3 and 5-HT1A receptors. Pharmacol Biochem Behav. 2013;112:49-55.
Krimon, S., Araldi, D., do Prado, F. C., Tambeli, C. H., Oliveira-Fusaro, M. C., & Parada, C. A. (2013). P2X3 receptors induced inflammatory nociception modulated by TRPA1, 5-HT3 and 5-HT1A receptors. Pharmacology, Biochemistry, and Behavior, 112, 49-55. https://doi.org/10.1016/j.pbb.2013.09.017
Krimon S, et al. P2X3 Receptors Induced Inflammatory Nociception Modulated By TRPA1, 5-HT3 and 5-HT1A Receptors. Pharmacol Biochem Behav. 2013;112:49-55. PubMed PMID: 24120766.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - P2X3 receptors induced inflammatory nociception modulated by TRPA1, 5-HT3 and 5-HT1A receptors. AU - Krimon,Suzy, AU - Araldi,Dionéia, AU - do Prado,Filipe César, AU - Tambeli,Cláudia Herrera, AU - Oliveira-Fusaro,Maria Cláudia G, AU - Parada,Carlos Amílcar, Y1 - 2013/10/09/ PY - 2013/05/04/received PY - 2013/09/06/revised PY - 2013/09/28/accepted PY - 2013/10/15/entrez PY - 2013/10/15/pubmed PY - 2014/7/17/medline KW - 5-HT3 receptors KW - Formalin KW - P2X3 receptors KW - TRPA1 receptors SP - 49 EP - 55 JF - Pharmacology, biochemistry, and behavior JO - Pharmacol Biochem Behav VL - 112 N2 - It has been described that endogenous ATP via activation of P2X3 and P2X2/3 receptors contributes to inflammatory nociception in different models, including the formalin injected in subcutaneous tissue of the rat's hind paw. In this study, we have evaluated whether TRPA1, 5-HT3 and 5-HT1A receptors, whose activation is essential to formalin-induced inflammatory nociception, are involved in the nociception induced by activation of P2X3 receptors on subcutaneous tissue of the rat's hind paw. We have also evaluated whether the activation of P2X3 receptors increases the susceptibility of primary afferent neurons to formalin action modulated by activation of TRPA1, 5-HT3 or 5-HT1A receptors. Nociceptive response intensity was measured by observing the rat's behavior and considering the number of times the animal reflexively raised its hind paw (flinches) in 60min. Local subcutaneous administration of the selective TRPA1, 5-HT3 or 5-HT1A receptor antagonists HC 030031, tropisetron and WAY 100,135, respectively, prevented the nociceptive responses induced by the administration in the same site of the non-selective P2X3 receptor agonist αβmeATP. Administration of the selective P2X3 and P2X2/3 receptor antagonist A-317491 or pretreatment with oligonucleotides antisense against P2X3 receptor prevented the formalin-induced behavioral nociceptive responses during the first and second phases. Also, the co-administration of a subthreshold dose of αβmeATP with a subthreshold dose of formalin induced nociceptive behavior, which was prevented by local administration of tropisetron, HC 030031 or WAY 100, 135. These findings have demonstrated that the activation of P2X3 receptors induces inflammatory nociception modulated by TRPA1, 5-HT3 and 5-HT1A receptors. Also, they suggest that inflammatory nociception is modulated by the release of endogenous ATP and P2X3 receptor activation, which in turn, increases primary afferent nociceptor susceptibility to the action of inflammatory mediators via interaction with TRPA1, 5-HT3 and 5-HT1A receptors in the peripheral tissue. SN - 1873-5177 UR - https://www.unboundmedicine.com/medline/citation/24120766/P2X3_receptors_induced_inflammatory_nociception_modulated_by_TRPA1_5_HT3_and_5_HT1A_receptors_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0091-3057(13)00233-5 DB - PRIME DP - Unbound Medicine ER -