TY - JOUR
T1 - Inhibition of peripheral anion exchanger 3 decreases formalin-induced pain
AU - Barragán-Iglesias, Paulino
AU - Rocha-González, Héctor I.
AU - Pineda-Farias, Jorge Baruch
AU - Murbartián, Janet
AU - Godínez-Chaparro, Beatriz
AU - Reinach, Peter S.
AU - Cunha, Thiago M.
AU - Cunha, Fernando Q.
AU - Granados-Soto, Vinicio
N1 - Funding Information:
Authors greatly appreciate the technical assistance of Guadalupe C. Vidal Cantú. This work is part of the M.Sc. dissertation of Paulino Barragán-Iglesias. Paulino Barragán-Iglesias and Jorge Baruch Pineda-Farias are Conacyt fellows. During his stay at the Department of Pharmacology, School of Medicine of Ribeirão Preto, University of Sao Paulo, Brazil, Paulino Barragán-Iglesias received the Beca mixta from Conacyt. Vinicio Granados-Soto and Peter S. Reinach are visiting professors at the Department of Pharmacology, School of Medicine of Ribeirão Preto, University of Sao Paulo, Brazil. Support by CNPq ( 400186/2011-0 ) is kindly acknowledged. This work was supported by the Grant 2011/19670-0 from São Paulo Research Foundation (FAPESP) . Partially supported by Conacyt CB-2012/179294 (VG-S), 154880 (HIR-G) and ICyTDF 332-2011 (JM) grants.
PY - 2014/9/5
Y1 - 2014/9/5
N2 - 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.
AB - 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.
KW - Acute nociception
KW - Chloride-bicarbonate anion exchanger 3
KW - Secondary allodynia
KW - Secondary hyperalgesia
UR - http://www.scopus.com/inward/record.url?scp=84902067157&partnerID=8YFLogxK
U2 - 10.1016/j.ejphar.2014.05.029
DO - 10.1016/j.ejphar.2014.05.029
M3 - Artículo
C2 - 24877687
SN - 0014-2999
VL - 738
SP - 91
EP - 100
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
ER -