title: Role of the spinal Na+/H+ exchanger in formalin-induced nociception.
abstract: This study assessed the role of the Na(+)/H(+) exchanger (NHE) in the formalin-induced nociception as well as the expression of the NHE isoform 1 (NHE1) in the rat spinal cord by using immunohistochemistry. Rats received a 50μl injection of diluted formalin (0.5%). Nociceptive behavior was quantified as the number of flinches of the injected paw. Intrathecal administration of the partially selective NHE1 inhibitors DMA, EIPA (0.3-30μM/rat) and the selective NHE1 inhibitor zoniporide (0.03-3μM/rat) significantly increased formalin-induced flinching behavior in a dose-dependent manner during both phases of the test. Immunohistochemical analysis of the rat lumbar spinal cord showed that NHE1 was mainly expressed in the lamina I of the dorsal horn of the spinal cord. Double immunofluorescence staining showed co-localization of NHE1 with the peptide-rich sensory nerve fiber markers, substance P and calcitonin gene-related peptide, but not with markers of neuronal cell bodies (NeuN), microglia (OX-42) or astroglia (GFAP). Collectively, these pharmacological and anatomical results suggest that spinal NHE1 plays a role in formalin-induced nociception acting as a protective protein extruding H(+).
authors.affiliation: Departamento de Farmacobiología, Cinvestav, Sede Sur, Calzada de los Tenorios 235, Colonia Granjas Coapa, 14330 México, D.F., Mexico.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Castañeda-Corral
authors.forename: Héctor I
authors.initials: HI
authors.lastname: Rocha-González
authors.forename: Beatriz
authors.initials: B
authors.lastname: Godínez-Chaparro
authors.forename: Juan Miguel
authors.initials: JM
authors.lastname: Jiménez-Andrade
authors.forename: Vinicio
authors.initials: V
authors.lastname: Granados-Soto
mesh_terms: D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005557:Formaldehyde / Q000633:toxicity*; D006146:Guanidines / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010146:Pain / Q000139:chemically induced / Q000378:metabolism*; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*
chemical_list: D006146:Guanidines; D011720:Pyrazoles; D017923:Sodium-Hydrogen Exchangers; D005557:Formaldehyde; C039465:5-dimethylamiloride; D000584:Amiloride; C424422:zoniporide; C039614:ethylisopropylamiloride