title: Inhibition of peripheral anion exchanger 3 decreases formalin-induced pain.
abstract: We determined the role of chloride-bicarbonate anion exchanger 3 in formalin-induced acute and chronic rat nociception. Formalin (1%) produced acute (first phase) and tonic (second phase) nociceptive behaviors (flinching and licking/lifting) followed by long-lasting evoked secondary mechanical allodynia and hyperalgesia in both paws. Local peripheral pre-treatment with the chloride-bicarbonate anion exchanger inhibitors 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid and 4-acetamido-4'-isothiocyanato-2,2'-stilbenedisulfonic acid prevented formalin-induced nociception mainly during phase 2. These drugs also prevented in a dose-dependent fashion long-lasting evoked secondary mechanical allodynia and hyperalgesia in both paws. Furthermore, post-treatment (on day 1 or 6) with 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid reversed established hypersensitivity. Anion exchanger 3 was expressed in dorsal root ganglion neurons and it co-localized with neuronal nuclei protein (NeuN), substance P and purinergic P2X3 receptors. Furthermore, Western blot analysis revealed a band of about 85 kDa indicative of anion exchanger 3 protein expression in dorsal root ganglia of naïve rats, which was enhanced at 1 and 6 days after 1% formalin injection. On the other hand, this rise failed to occur during 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid exposure. These results suggest that anion exchanger 3 is present in dorsal root ganglia and participates in the development and maintenance of short and long-lasting formalin-induced nociception.
authors.affiliation: Neurobiology of Pain Laboratory, Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados (Cinvestav), Sede Sur, México, D.F., Mexico.
authors.forename: Paulino
authors.initials: P
authors.lastname: Barragán-Iglesias
authors.affiliation: Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, México, D.F., Mexico.
authors.forename: Héctor I
authors.initials: HI
authors.lastname: Rocha-González
authors.affiliation: Neurobiology of Pain Laboratory, Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados (Cinvestav), Sede Sur, México, D.F., Mexico.
authors.forename: Jorge Baruch
authors.initials: JB
authors.lastname: Pineda-Farias
authors.affiliation: Neurobiology of Pain Laboratory, Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados (Cinvestav), Sede Sur, México, D.F., Mexico.
authors.forename: Janet
authors.initials: J
authors.lastname: Murbartián
authors.affiliation: Departamento de Sistemas Biológicos, División de Ciencias Biológicas y de la Salud, Universidad Autónoma Metropolitana-Xochimilco, México, D.F., Mexico.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Godínez-Chaparro
authors.affiliation: Department of Pharmacology, Riberao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Reinach
authors.affiliation: Department of Pharmacology, Riberao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil.
authors.forename: Thiago M
authors.initials: TM
authors.lastname: Cunha
authors.affiliation: Department of Pharmacology, Riberao Preto Medical School, University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil.
authors.forename: Fernando Q
authors.initials: FQ
authors.lastname: Cunha
authors.affiliation: Neurobiology of Pain Laboratory, Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados (Cinvestav), Sede Sur, México, D.F., Mexico. Electronic address: vgranados@prodigy.net.mx.
authors.forename: Vinicio
authors.initials: V
authors.lastname: Granados-Soto
mesh_terms: D000818:Animals; D027963:Chloride-Bicarbonate Antiporters / Q000378:metabolism*; D005260:Female; D005557:Formaldehyde / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D059225:Nociception / Q000187:drug effects; D010146:Pain / Q000139:chemically induced* / Q000378:metabolism* / Q000503:physiopathology; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013451:Sulfonic Acids / Q000494:pharmacology
chemical_list: D027963:Chloride-Bicarbonate Antiporters; D013451:Sulfonic Acids; D005557:Formaldehyde
keywords: Acute nociception; Chloride–bicarbonate anion exchanger 3; Secondary allodynia; Secondary hyperalgesia