Effect of econazole and benzydamine on sensory neurons in culture.

Mathivanan, S; de la Torre-Martinez, R; Wolf, C; Mangano, G; Polenzani, L; Milanese, C; Ferrer-Montiel, A

Mathivanan, S; de la Torre-Martinez, R; Wolf, C; Mangano, G; Polenzani, L; Milanese, C; Ferrer-Montiel, A.

Afiliación

Mathivanan S; Institute of Molecular and Cell Biology, Miguel Hernandez University, Alicante, Spain. aferrer@umh.es.
de la Torre-Martinez R; Institute of Molecular and Cell Biology, Miguel Hernandez University, Alicante, Spain.
Wolf C; Institute of Molecular and Cell Biology, Miguel Hernandez University, Alicante, Spain.
Mangano G; Angelini Research Center, Angelini S.p.A., S. Palomba-Pomezia (Rome), Italy.
Polenzani L; Angelini Research Center, Angelini S.p.A., S. Palomba-Pomezia (Rome), Italy.
Milanese C; Angelini Research Center, Angelini S.p.A., S. Palomba-Pomezia (Rome), Italy.
Ferrer-Montiel A; Institute of Molecular and Cell Biology, Miguel Hernandez University, Alicante, Spain.

J Physiol Pharmacol ; 67(6): 851-858, 2016 Dec.

Article en En | MEDLINE | ID: mdl-28195065

RESUMEN

Econazole is an anti-mycotic agent widely used for the treatment of cutaneous fungal infections, and for the therapy of vaginal candidiasis. Topical application of this azole is generally safe, although some patients have complained of mild burning sensation/cutaneous irritation and itching, especially when administered intravaginally. The underlying mechanisms responsible of these adverse effects are poorly understood, though they suggest excitation of cutaneous nociceptor terminals. We report that exposure of primary cultures of rat nociceptors to econazole augments neuronal excitability. This effect appears mediated by increments in the intracellular Ca2+ by stimulating Ca2+ entry and release from the endoplasmic reticulum. Ca2+ entry was not due to activation of thermo transient receptor potential (TRP) channels, suggesting a different ion channel targeted by the azole. Noteworthy, econazole-evoked responses were potentiated by a pro-inflammatory agent, which resulted in an increase in neuronal excitability. Econazole-elicited action potential firing was significantly abolished by the inflammatory cytokine inhibiting drug benzydamine via blockade of voltage-gated Na+ (Nav) channels. Collectively, our results indicate that the burning sensation of econazole is due at least in part to modulation of nociceptor excitability, and such sensation is increased in the presence of pro-inflammatory stimuli and blocked by benzydamine. These findings imply that a combination of the azole with benzydamine has the potential to reduce significantly the unpleasant symptoms related to infection and to the adverse effects of topical econazole formulations.

Asunto(s)

Bencidamina/farmacología; Econazol/farmacología; Células Receptoras Sensoriales/efectos de los fármacos; Animales; Antifúngicos/farmacología; Calcio/metabolismo; Células Cultivadas; Citocinas/metabolismo; Retículo Endoplásmico/efectos de los fármacos; Retículo Endoplásmico/metabolismo; Inflamación/tratamiento farmacológico; Inflamación/metabolismo; Nociceptores/efectos de los fármacos; Nociceptores/metabolismo; Ratas; Ratas Wistar; Células Receptoras Sensoriales/metabolismo; Canales de Potencial de Receptor Transitorio/metabolismo

Buscar en Google

Añadir a Mi BVS

Imprimir

XML

PubMed Links

Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Receptoras Sensoriales / Bencidamina / Econazol Límite: Animals Idioma: En Revista: J Physiol Pharmacol Asunto de la revista: FARMACOLOGIA / FISIOLOGIA Año: 2016 Tipo del documento: Article País de afiliación: España Pais de publicación: Polonia

Buscar en Google

Añadir a Mi BVS

Imprimir

XML

PubMed Links