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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.