Evidence for the participation of Ca(2+)-activated chloride channels in formalin-induced acute and chronic nociception.

Abstract

In this study we determined the role of Ca(2+)-activated chloride channels (CaCC) in acute and chronic nociceptive responses elicited by 1% formalin. Formalin injection produced a typical pattern of flinching behavior for about 1h. Moreover, it produced secondary allodynia and hyperalgesia in the ipsilateral and contralateral paws for at least 6 days. Local peripheral and intrathecal pre-treatment (-10 min) with the non-selective and selective CaCC blockers niflumic acid and CaCCinh-A01, respectively, prevented formalin-induced flinching behavior mainly during phase 2 of the formalin test. Furthermore, niflumic acid and CaCCinh-A01 also prevented in a dose-dependent manner the long-lasting evoked secondary mechanical allodynia and hyperalgesia in the ipsilateral and contralateral paws. Moreover, local peripheral and intrathecal post-treatment (on day 6) with both CaCC blockers decreased the established formalin-induced secondary mechanical allodynia and hyperalgesia behavior in both paws. CaCC anoctamin-1 and bestrophin-1 were detected in the dorsal root ganglia. Formalin injection increased anoctamin-1, but not bestrophin-1 protein levels at 6 days. Intrathecal injection of the CaCC inhibitor CaCCinh-A01 prevented formalin-induced anoctamin-1 increase. Data suggest that peripheral and spinal CaCC, and particularly anoctamin-1, participates in the acute nociception induced by formalin as well as in the development and maintenance of secondary mechanical allodynia and hyperalgesia. Thus, CaCC activity contributes to neuronal excitability in the process of nociception induced by formalin.

• Authors: Guadalupe García, Vladimir A Martínez-Rojas, Héctor I Rocha-González, Vinicio Granados-Soto, Janet Murbartián
• Journal: Brain research (Brain Res) Vol. 1579 Pg. 35-44 (Sep 04 2014) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 25036442 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• ANO1 protein, rat
• Anoctamin-1
• Chloride Channels
• Formaldehyde
• Niflumic Acid

Topics

• Animals
• Anoctamin-1
• Chloride Channels (metabolism)
• Female
• Formaldehyde (toxicity)
• Ganglia, Spinal (drug effects, metabolism, physiopathology)
• Hyperalgesia (chemically induced, metabolism, physiopathology)
• Niflumic Acid (pharmacology)
• Nociception (drug effects, physiology)
• Pain Measurement
• Rats
• Rats, Wistar