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TRPA1, substance P, histamine and 5-hydroxytryptamine interact in an interdependent way to induce nociception.
Inflamm Res. 2017 Apr; 66(4):311-322.IR

Abstract

BACKGROUND

Although TRPA1, SP, histamine and 5-hydroxytryptamine (5-HT) have recognized contribution to nociceptive mechanisms, little is known about how they interact with each other to mediate inflammatory pain in vivo. In this study we evaluated whether TRPA1, SP, histamine and 5-HT interact, in an interdependent way, to induce nociception in vivo.

METHODS AND RESULTS

The subcutaneous injection of the TRPA1 agonist allyl isothiocyanate (AITC) into the rat's hind paw induced a dose-dependent and short lasting behavioral nociceptive response that was blocked by the co-administration of the TRPA1 antagonist, HC030031, or by the pretreatment with antisense ODN against TRPA1. AITC-induced nociception was significantly decreased by the co-administration of selective antagonists for the NK1 receptor for substance P, the H1 receptor for histamine and the 5-HT1A or 3 receptors for 5-HT. Histamine- or 5-HT-induced nociception was decreased by the pretreatment with antisense ODN against TRPA1. These findings suggest that AITC-induced nociception depends on substance P, histamine and 5-HT, while histamine- or 5-HT-induced nociception depends on TRPA1. Most important, AITC interact in a synergistic way with histamine, 5-HT or substance P, since their combination at non-nociceptive doses induced a nociceptive response much higher than that expected by the sum of the effect of each one alone. This synergistic effect is dependent on the H1, 5-HT1A or 3 receptors.

CONCLUSION

Together, these findings suggest a self-sustainable cycle around TRPA1, no matter where the cycle is initiated each step is achieved and even subeffective activation of more than one step results in a synergistic activation of the overall cycle.

Authors+Show Affiliations

Division of Biological Sciences, Department of Physiology, Federal University of Parana, Curitiba, Parana, Brazil. fischer@ufpr.br.Division of Biological Sciences, Department of Physiology, Federal University of Parana, Curitiba, Parana, Brazil.Division of Biological Sciences, Department of Physiology, Federal University of Parana, Curitiba, Parana, Brazil.Division of Biological Sciences, Department of Physiology, Federal University of Parana, Curitiba, Parana, Brazil.Division of Biological Sciences, Department of Physiology, Federal University of Parana, Curitiba, Parana, Brazil.Division of Biological Sciences, Department of Physiology, Federal University of Parana, Curitiba, Parana, Brazil.Department Functional and Structural Biology, Institute of Biology, State University of Campinas-UNICAMP, Campinas, São Paulo, Brazil.Department Functional and Structural Biology, Institute of Biology, State University of Campinas-UNICAMP, Campinas, São Paulo, Brazil.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27904941

Citation

Fischer, Luana, et al. "TRPA1, Substance P, Histamine and 5-hydroxytryptamine Interact in an Interdependent Way to Induce Nociception." Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.], vol. 66, no. 4, 2017, pp. 311-322.
Fischer L, Lavoranti MI, de Oliveira Borges M, et al. TRPA1, substance P, histamine and 5-hydroxytryptamine interact in an interdependent way to induce nociception. Inflamm Res. 2017;66(4):311-322.
Fischer, L., Lavoranti, M. I., de Oliveira Borges, M., Miksza, A. F., Sardi, N. F., Martynhak, B. J., Tambeli, C. H., & Parada, C. A. (2017). TRPA1, substance P, histamine and 5-hydroxytryptamine interact in an interdependent way to induce nociception. Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.], 66(4), 311-322. https://doi.org/10.1007/s00011-016-1015-1
Fischer L, et al. TRPA1, Substance P, Histamine and 5-hydroxytryptamine Interact in an Interdependent Way to Induce Nociception. Inflamm Res. 2017;66(4):311-322. PubMed PMID: 27904941.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - TRPA1, substance P, histamine and 5-hydroxytryptamine interact in an interdependent way to induce nociception. AU - Fischer,Luana, AU - Lavoranti,Maria Isabel, AU - de Oliveira Borges,Mariana, AU - Miksza,Alana Farias, AU - Sardi,Natalia Fantin, AU - Martynhak,Bruno Jacson, AU - Tambeli,Claudia H, AU - Parada,Carlos Amílcar, Y1 - 2016/11/30/ PY - 2016/07/27/received PY - 2016/11/25/accepted PY - 2016/11/23/revised PY - 2016/12/3/pubmed PY - 2017/7/28/medline PY - 2016/12/2/entrez KW - 5-Hydroxytryptamine (5-HT) KW - Histamine KW - Nociception KW - Substance P KW - TRPA1 SP - 311 EP - 322 JF - Inflammation research : official journal of the European Histamine Research Society ... [et al.] JO - Inflamm Res VL - 66 IS - 4 N2 - BACKGROUND: Although TRPA1, SP, histamine and 5-hydroxytryptamine (5-HT) have recognized contribution to nociceptive mechanisms, little is known about how they interact with each other to mediate inflammatory pain in vivo. In this study we evaluated whether TRPA1, SP, histamine and 5-HT interact, in an interdependent way, to induce nociception in vivo. METHODS AND RESULTS: The subcutaneous injection of the TRPA1 agonist allyl isothiocyanate (AITC) into the rat's hind paw induced a dose-dependent and short lasting behavioral nociceptive response that was blocked by the co-administration of the TRPA1 antagonist, HC030031, or by the pretreatment with antisense ODN against TRPA1. AITC-induced nociception was significantly decreased by the co-administration of selective antagonists for the NK1 receptor for substance P, the H1 receptor for histamine and the 5-HT1A or 3 receptors for 5-HT. Histamine- or 5-HT-induced nociception was decreased by the pretreatment with antisense ODN against TRPA1. These findings suggest that AITC-induced nociception depends on substance P, histamine and 5-HT, while histamine- or 5-HT-induced nociception depends on TRPA1. Most important, AITC interact in a synergistic way with histamine, 5-HT or substance P, since their combination at non-nociceptive doses induced a nociceptive response much higher than that expected by the sum of the effect of each one alone. This synergistic effect is dependent on the H1, 5-HT1A or 3 receptors. CONCLUSION: Together, these findings suggest a self-sustainable cycle around TRPA1, no matter where the cycle is initiated each step is achieved and even subeffective activation of more than one step results in a synergistic activation of the overall cycle. SN - 1420-908X UR - https://www.unboundmedicine.com/medline/citation/27904941/TRPA1_substance_P_histamine_and_5_hydroxytryptamine_interact_in_an_interdependent_way_to_induce_nociception_ L2 - https://dx.doi.org/10.1007/s00011-016-1015-1 DB - PRIME DP - Unbound Medicine ER -