Behavior of ion channels controlled by electric potential difference and of Toll-type receptors in neuropathic pain pathophysiology

Abstract

BACKGROUND AND OBJECTIVES:Neuropathic pain is a severe and refractory medical condition, for which only partially effective treatments are currently available. Recent experimental data on the role of voltage-gated ion channels, particularly sodium and potassium channels, have been described. In this brief review, we aimed at addressing the role of sodium and potassium channels in the pathophysiology of neuropathic pain and recent evidences about their role as a new therapeutic target in painful conditions. CONTENTS: Pharmacological and biophysical studies have shown that voltagegated sodium channels, particularly Na v 1.3, Na v 1.7, Na v 1.8, and Na v 1.9 isoforms are important in the pathophysiology of neuropathic pain. Similarly, the involvement of voltage-gated potassium channels, especially K V 1 and K V 7 isoforms, has been clearly shown in the establishment of chronic painful conditions. Recent evidences that ion sodium and potassium channels dysfunction is involved in the development of chronic painful conditions corroborate the possibility of pharmacologically modulate them as new therapeutic strategies. CONCLUSION: Recent evidences suggest that selective sodium channel blockers and potassium channels activating of modulating drugs are important and promising targets in the search for new options to treat neuropathic pain. Keywords: Chronic pain, Ion channels, Neuropathic pain, Potassium channels, Sodium channels. RESUMO JUSTIFICATIVA E OBJETIVOS:A dor neuropática constitui-se em uma condição clínica grave e refratária, para a qual apenas tratamentos com eficácia parcial estão disponíveis. Estudos experimentais recentes sobre o papel relevante de canais iônicos controlados por diferença de potencial elétrico ou voltagem, especialmente canais de sódio e potássio, tem sido descritos. Nesta breve revisão, objetivou-se abordar o papel dos canais de sódio e potássio na fisiopatologia da dor neuropática e as recentes evidências a respeito do seu papel como novo alvo terapêutico em quadros dolorosos. CONTEÚDO: Estudos farmacológicos e biofísicos tem demonstrado que os canais de sódio dependentes de voltagem, particularmente as isoformas Na v 1.3, Na v 1.7, Na v 1.8 e Na v 1.9 são relevantes na fisiopatologia da dor neuropática. De forma similar, o envolvimento dos canais de potássio dependentes de voltagem, especialmente as isoformas K v 1 e K v 7, tem sido claramente demonstrado no estabelecimento de quadros dolorosos crônicos. As evidências recentes de que a disfunção de canais iônicos de sódio e potássio está envolvida no desenvolvi- Behavior of ion channels controlled by electric potential difference and of Toll-type receptors in neuropathic pain pathophysiology O comportamento dos canais iônicos controlados por diferença de potencial elétrico e dos receptores do tipo Toll na fisiopatologia da dor neuropática

A whole genome sequencing approach to anterior cruciate ligament rupture–a twin study in two unrelated families

“…Interestingly, 3D protein structure simulation analysis ( Fig 3 and S2 Fig ) illustrates the rigidity of the mutated structures for these potassium and ion-channel related genes, potential mutations have an impact binding interactions, stability, and conformation of these proteins. Also these potassium and ion-channel related genes, and their dysfunction have been implicated in the development of chronic pain conditions [ 29 , 30 ] and subsequently identified as potential therapeutic targets for painful conditions [ 31 ]. Even more, ion channels modulate membrane ion conductance across all cells and tissues, establishing electrical fields that affect cellular behaviours under normal conditions, during critical periods of development, and in response to tissue injury [ 32 ].…”