Role of Anoctamin-1 and Bestrophin-1 in Spinal Nerve Ligation-Induced Neuropathic Pain in Rats

• Published in: Molecular pain 2015-07, Vol.11, p.41-41
• Main Authors: Pineda-Farias, Jorge Baruch, Barragan-Iglesias, Paulino, Loeza-Alcocer, Emanuel, Torres-Lopez, Jorge E, Rocha-Gonzalez, Héctor Isaac, Perez-Severiano, Francisca, Delgado-Lezama, Rodolfo, Granados-Soto, Vinicio
• Format: Article
• Language: English
• Subjects: Action potential; Analgesia; Animals; Anoctamin-1; Bestrophins; Calcium channels; Calcium chloride; Chloride channels (calcium-gated); Chloride Channels - antagonists & inhibitors; Chloride Channels - genetics; Chloride Channels - metabolism; Depolarization; Dorsal root ganglia; Female; Fibers; Gene expression; Hyperalgesia; Hyperalgesia - complications; Hyperalgesia - pathology; Hyperalgesia - physiopathology; Inflammation; Injections, Spinal; Ligation; Membrane potential; Motor Activity; mRNA; Neural Conduction; Neuralgia; Neuralgia - complications; Neuralgia - metabolism; Neuralgia - pathology; Neuralgia - physiopathology; Pain; Pain perception; Protein expression; Proteins; Rats, Wistar; RNA, Messenger - genetics; RNA, Messenger - metabolism; Sensory neurons; Spinal cord; Spinal Cord - drug effects; Spinal Cord - metabolism; Spinal Cord - pathology; Spinal Cord - physiopathology; Spinal nerves; Spinal Nerves - injuries; Spinal Nerves - pathology; Spinal Nerves - physiopathology; Tactile stimuli
• ISSN: 1744-8069; 1744-8069
• DOI: 10.1186/s12990-015-0042-1

Background Calcium-activated chloride channels (CaCCs) activation induces membrane depolarization by increasing chloride efflux in primary sensory neurons that can facilitate action potential generation. Previous studies suggest that CaCCs family members bestrophin-1 and anoctamin-1 are involved in inflammatory pain. However, their role in neuropathic pain is unclear. In this investigation we assessed the involvement of these CaCCs family members in rats subjected to the L5/L6 spinal nerve ligation. In addition, anoctamin-1 and bestrophin-1 mRNA and protein expression in dorsal root ganglion (DRG) and spinal cord was also determined in the presence and absence of selective inhibitors. Results L5/L6 spinal nerve ligation induced mechanical tactile allodynia. Intrathecal administration of non-selective CaCCs inhibitors (NPPB, 9-AC and NFA) dose-dependently reduced tactile allodynia. Intrathecal administration of selective CaCCs inhibitors (T16Ainh-A01 and CaCCinh-A01) also dose-dependently diminished tactile allodynia and thermal hyperalgesia. Anoctamin-1 and bestrophin-1 mRNA and protein were expressed in the dorsal spinal cord and DRG of naïve, sham and neuropathic rats. L5/L6 spinal nerve ligation rose mRNA and protein expression of anoctamin-1, but not bestrophin-1, in the dorsal spinal cord and DRG from day 1 to day 14 after nerve ligation. In addition, repeated administration of CaCCs inhibitors (T16Ainh-A01, CaCCinh-A01 or NFA) or anti-anoctamin-1 antibody prevented spinal nerve ligation-induced rises in anoctamin-1 mRNA and protein expression. Following spinal nerve ligation, the compound action potential generation of putative C fibers increased while selective CaCCs inhibitors (T16Ainh-A01 and CaCCinh-A01) attenuated such increase. Conclusions There is functional anoctamin-1 and bestrophin-1 expression in rats at sites related to nociceptive processing. Blockade of these CaCCs suppresses compound action potential generation in putative C fibers and lessens established tactile allodynia. As CaCCs activity contributes to neuropathic pain maintenance, selective inhibition of their activity may function as a tool to generate analgesia in nerve injury pain states.