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Functional aspects and mechanisms of TRPV1 involvement in neurogenic inflammation that leads to thermal hyperalgesia

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Abstract

Neurogenic inflammation is produced by overstimulation of peripheral nociceptor terminals by injury or inflammation of tissues. Excessive activity of sensory neurons produces vasodilation, plasma extravasation and hypersensitivity. Mechanistically, neurogenic inflammation is due to the release of substances from primary sensory nerve terminals that act directly or indirectly at the peripheral terminals, either activating or sensitizing nociceptors, endothelial cells and immunocytes. Notably, small-diameter sensory neurons that are sensitive to capsaicin play a key role in the generation of neurogenic inflammation. The cloning of the vanilloid receptor 1 (TRPV1) has been a breakthrough that has propelled our understanding of the molecular mechanisms involved in neurogenic inflammation. TRPV1 pivotally contributes to the integration of various stimuli and modulates nociceptor excitability, thus making it a true gateway for pain transduction. In addition, TRPV1 is the endpoint target of intracellular signalling pathways triggered by inflammatory mediators. Phosphorylation-induced potentiation of TRPV1 channel activity, along with an incremented TRPV1 surface expression are major events underlying the nociceptor activation and sensitization that leads to thermal hyperalgesia. The important contribution of TRPV1 receptor to the onset and maintenance of neurogenic inflammation has validated it as a therapeutic target for inflammatory pain management. As a result, the development of specific TRPV1 antagonists is a central focus of current drug discovery programs.

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Acknowledgements

We thank all members of our group and colleagues of collaboration groups for their fundamental contribution to the results herein presented. We are indebted to the financial support from the MCYT, FIS, GVA and Fundació La Caixa.

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  1. Centro de Investigación Príncipe Felipe, FVIB, 46012, Valencia, Spain

    Rosa Planells-Cases

  2. Instituto Biología Molecular y Celular, Universidad Miguel Hernández, Av. De la Universidad s/n, 03202, Elche, Alicante, Spain

    Nuria Garcìa-Sanz, Cruz Morenilla-Palao & Antonio Ferrer-Montiel

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  1. Rosa Planells-Cases
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  2. Nuria Garcìa-Sanz
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  3. Cruz Morenilla-Palao
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Correspondence to Antonio Ferrer-Montiel.

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Planells-Cases, R., Garcìa-Sanz, N., Morenilla-Palao, C. et al. Functional aspects and mechanisms of TRPV1 involvement in neurogenic inflammation that leads to thermal hyperalgesia. Pflugers Arch - Eur J Physiol 451, 151–159 (2005). https://doi.org/10.1007/s00424-005-1423-5

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