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Pain Research and Treatment
Volume 2013, Article ID 217864, 8 pages
Review Article

Role of NHE1 in Nociception

1Centro de Investigación y Posgrado y División Académica de Ciencias de la Salud, Universidad Juárez Autónoma de Tabasco, 86040 Villahermosa, TAB, Mexico
2Hospital Regional de Alta Especialidad “Dr. Juan Graham Casasús”, 86126 Villahermosa, TAB, Mexico
3Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, 11340 México, DF, Mexico
4Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados (Cinvestav), Sede Sur, Calzada Tenorios 235, Colonia Granjas Coapa, 14330 México, DF, Mexico

Received 29 August 2012; Accepted 2 January 2013

Academic Editor: Pierangelo Geppetti

Copyright © 2013 Jorge Elías Torres-López et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Intracellular pH is a fundamental parameter to cell function that requires tight homeostasis. In the absence of any regulation, excessive acidification of the cytosol would have the tendency to produce cellular damage. Mammalian Na+/H+ exchangers (NHEs) are electroneutral Na+-dependent proteins that exchange extracellular Na+ for intracellular H+. To date, there are 9 identified NHE isoforms where NHE1 is the most ubiquitous member, known as the housekeeping exchanger. NHE1 seems to have a protective role in the ischemia-reperfusion injury and other inflammatory diseases. In nociception, NHE1 is found in neurons along nociceptive pathways, and its pharmacological inhibition increases nociceptive behavior in acute pain models at peripheral and central levels. Electrophysiological studies also show that NHE modulates electrical activity of primary nociceptive terminals. However, its role in neuropathic pain still remains controversial. In humans, NHE1 may be responsible for inflammatory bowel diseases since its expression is reduced in Crohn’s disease and ulcerative colitis. The purpose of this work is to provide a review of the evidence about participation of NHE1 in the nociceptive processing.