Role of anoctamin-1 and bestrophin-1 in spinal nerve ligation-induced neuropathic pain in rats

Molecular Pain

Vinicio Granados-Soto³  Rodolfo Delgado-Lezama²  Francisca Pérez-Severiano⁴  Héctor Isaac Rocha-González⁵  Jorge E Torres-López¹  Emanuel Loeza-Alcocer²  Paulino Barragán-Iglesias³  Jorge Baruch Pineda-Farias³ 

[1] Hospital Regional de Alta Especialidad “Dr. Juan Graham Casasús”, Villahermosa, Tabasco, México;Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados (Cinvestav), Zacatenco, México, D.F., México;Neurobiology of Pain Laboratory, Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados (Cinvestav), Sede Sur, Calzada de los Tenorios 235, Colonia Granjas Coapa, México, D.F., 14330, México;Departamento de Neuroquímica, Instituto Nacional de Neurología y Neurocirugía “Manuel Velasco Suárez”, México, D.F., México;Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, México, D.F., México

关键词: Spinal nerve ligation;    Neuropathic pain;    Calcium-activated chloride channels;    Bestrophin-1;    Anoctamin-1;    Allodynia;   

Others  :  1217320
DOI  :  10.1186/s12990-015-0042-1

 received in 2015-02-10, accepted in 2015-06-11,  发布年份 2015

【 摘 要 】

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 (T16A _inh -A01 and CaCC _inh -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 (T16A _inh -A01, CaCC _inh -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 (T16A _inh -A01 and CaCC _inh -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.

【 授权许可】

   
2015 Pineda-Farias et al.

【 图 表 】

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【 参考文献 】

• [1]Treede RD, Jensen TS, Campbell JN, Cruccu G, Dostrovsky JO, Griffin JW, et al.: Neuropathic pain: redefinition and a grading system for clinical and research purposes. Neurology 2008, 70:1630-1635.
• [2]Latremoliere A, Woolf CJ: Central sensitization: a generator of pain hypersensitivity by central neural plasticity. J Pain 2009, 10:895-926.
• [3]Basbaum AI, Bautista DM, Scherrer G, Julius D: Cellular and molecular mechanisms of pain. Cell 2009, 139:267-284.
• [4]Gangadharan V, Kuner R: Pain hypersensitivity mechanisms at a glance. Dis Model Mech 2013, 6:889-895.
• [5]Price TJ, Cervero F, Gold MS, Hammond DL, Prescott SA: Chloride regulation in the pain pathway. Brain Res Rev 2009, 60:149-170.
• [6]Waxman SG, Zamponi GW: Regulating excitability of peripheral afferents: emerging ion channel targets. Nat Neurosci 2014, 17:153-163.
• [7]Caputo A, Caci E, Ferrera L, Pedemonte N, Barsanti C, Sondo E, et al.: TMEM16A, a membrane protein associated with calcium-dependent chloride channel activity. Science 2008, 322:590-594.
• [8]Schroeder BC, Cheng T, Jan YN, Jan LY: Expression cloning of TMEM16A as a calcium-activated chloride channel subunit. Cell 2008, 134:1019-1029.
• [9]Yang YD, Cho H, Koo JY, Tak MH, Cho Y, Shim WS, et al.: TMEM16A confers receptor-activated calcium-dependent chloride conductance. Nature 2008, 455:1210-1215.
• [10]Petrukhin K, Koisti MJ, Bakall B, Li W, Xie G, Marknell T, et al.: Identification of the gene responsible for best macular dystrophy. Nat Genet 1998, 19:241-247.
• [11]Sun H, Tsunenari T, Yau KW, Nathans J: The vitelliform macular dystrophy protein defines a new family of chloride channels. Proc Natl Acad Sci USA 2002, 99:4008-4013.
• [12]Park H, Oh SJ, Han KS, Woo DH, Mannaioni G, Traynelis SF, et al.: Bestrophin-1 encodes for the Ca 2+ -activated anion channel in hippocampal astrocytes. J Neurosci 2009, 29:13063-13073.
• [13]Hartzell C, Putzier I, Arreola J: Calcium-activated chloride channels. Annu Rev Physiol 2005, 67:719-758.
• [14]Leblanc N, Ledoux J, Saleh S, Sanguinetti A, Angermann J, O’Driscoll K, et al.: Regulation of calcium-activated chloride channels in smooth muscle cells: a complex picture is emerging. Can J Physiol Pharmacol 2005, 83:541-556.
• [15]Frings S, Reuter D, Kleene SJ: Neuronal Ca 2+ -activated Cl − channels-homing in on an elusive channel species. Prog Neurobiol 2000, 60:247-289.
• [16]Eggermont J: Calcium-activated chloride channels: (un)known, (un)loved? Proc Am Thorac Soc 2004, 1:22-27.
• [17]Kidd JF, Thorn P: Intracellular Ca 2+ and Cl − channel activation in secretory cells. Annu Rev Physiol 2000, 62:493-513.
• [18]Melvin JE, Yule D, Shuttleworth T, Begenisich T: Regulation of fluid and electrolyte secretion in salivary gland acinar cells. Annu Rev Physiol 2005, 67:445-469.
• [19]Liu B, Linley JE, Du X, Zhang X, Ooi L, Zhang H, et al.: The acute nociceptive signals induced by bradykinin in rat sensory neurons are mediated by inhibition of M-type K + channels and activation of Ca 2+ -activated Cl − channels. J Clin Invest 2010, 120:1240-1252.
• [20]Cho H, Yang YD, Lee J, Lee B, Kim T, Jang Y, et al.: The calcium-activated chloride channel anoctamin 1 acts as a heat sensor in nociceptive neurons. Nat Neurosci 2012, 15:1015-1021.
• [21]Lee B, Cho H, Jung J, Yang YD, Yang DJ, Oh U: Anoctamin 1 contributes to inflammatory and nerve-injury induced hypersensitivity. Mol Pain 2014, 10:5. BioMed Central Full Text
• [22]Al-Jumaily M, Kozlenkov A, Mechaly I, Fichard A, Matha V, Scamps F, et al.: Expression of three distinct families of calcium-activated chloride channel genes in the mouse dorsal root ganglion. Neurosci Bull 2007, 23:293-299.
• [23]Boudes M, Sar C, Menigoz A, Hilaire C, Pequignot MO, Kozlenkov A, et al.: Best1 is a gene regulated by nerve injury and required for Ca 2+ -activated Cl − current expression in axotomized sensory neurons. J Neurosci 2009, 29:10063-10071.
• [24]Garcia G, Martinez-Rojas VA, Rocha-Gonzalez HI, Granados-Soto V, Murbartian J: Evidence for the participation of Ca 2+ -activated chloride channels in formalin-induced acute and chronic nociception. Brain Res 2014, 1579:35-44.
• [25]Mayer ML: A calcium-activated chloride current generates the after-depolarization of rat sensory neurones in culture. J Physiol 1985, 364:217-239.
• [26]Scott RH, Sutton KG, Griffin A, Stapleton SR, Currie KP: Aspects of calcium-activated chloride currents: a neuronal perspective. Pharmacol Ther 1995, 66:535-565.
• [27]Granados-Soto V, Arguelles CF, Alvarez-Leefmans FJ: Peripheral and central antinociceptive action of Na + –K + –2Cl − cotransporter blockers on formalin-induced nociception in rats. Pain 2005, 114:231-238.
• [28]Andre S, Boukhaddaoui H, Campo B, Al-Jumaily M, Mayeux V, Greuet D, et al.: Axotomy-induced expression of calcium-activated chloride current in subpopulations of mouse dorsal root ganglion neurons. J Neurophysiol 2003, 90:3764-3773.
• [29]Caram-Salas NL, Reyes-Garcia G, Bartoszyk GD, Araiza-Saldana CI, Ambriz-Tututi M, Rocha-Gonzalez HI, et al.: Subcutaneous, intrathecal and periaqueductal grey administration of asimadoline and ICI-204448 reduces tactile allodynia in the rat. Eur J Pharmacol 2007, 573:75-83.
• [30]Zimmermann M: Ethical guidelines for investigations of experimental pain in conscious animals. Pain 1983, 16:109-110.
• [31]Kim SH, Chung JM: An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat. Pain 1992, 50:355-363.
• [32]Chaplan SR, Bach FW, Pogrel JW, Chung JM, Yaksh TL: Quantitative assessment of tactile allodynia in the rat paw. J Neurosci Methods 1994, 53:55-63.
• [33]Dixon WJ: Efficient analysis of experimental observations. Annu Rev Pharmacol Toxicol 1980, 20:441-462.
• [34]Dirig DM, Salami A, Rathbun ML, Ozaki GT, Yaksh TL: Characterization of variables defining hindpaw withdrawal latency evoked by radiant thermal stimuli. J Neurosci Methods 1997, 76:183-191.
• [35]Pineda-Farias JB, Perez-Severiano F, Gonzalez-Esquivel DF, Barragan-Iglesias P, Bravo-Hernandez M, Cervantes-Duran C, et al.: The L-kynurenine-probenecid combination reduces neuropathic pain in rats. Eur J Pain 2013, 17:1365-1373.
• [36]Yaksh TL, Rudy TA: Chronic catheterization of the spinal subarachnoid space. Physiol Behav 1976, 17:1031-1036.
• [37]Choi-Lundberg DL, Bohn MC: Ontogeny and distribution of glial cell line-derived neurotrophic factor (GDNF) mRNA in rat. Brain Res Dev Brain Res 1995, 85:80-88.
• [38]Lowry OH, Rosebrough NJ, Farr AL, Randall RJ: Protein measurement with the Folin phenol reagent. J Biol Chem 1951, 193:265-275.
• [39]Lee JH, Park CK, Chen G, Han Q, Xie RG, Liu T, et al.: A monoclonal antibody that targets a NaV1.7 channel voltage sensor for pain and itch relief. Cell 2014, 157:1393-1404.
• [40]Shen W, Hu XM, Liu YN, Han Y, Chen LP, Wang CC, et al.: CXCL12 in astrocytes contributes to bone cancer pain through CXCR4-mediated neuronal sensitization and glial activation in rat spinal cord. J Neuroinflammation 2014, 11:75. BioMed Central Full Text
• [41]Nasirinezhad F, Gajavelli S, Priddy B, Jergova S, Zadina J, Sagen J: Viral vectors encoding endomorphins and serine histogranin attenuate neuropathic pain symptoms after spinal cord injury in rats. Mol Pain 2015, 11:2. BioMed Central Full Text
• [42]Tallarida RJ: Drug synergism and dose-effect data analysis. Chapman Hall/CRC Press, Boca Raton; 2000.
• [43]Sapunar D, Ljubkovic M, Lirk P, McCallum JB, Hogan QH: Distinct membrane effects of spinal nerve ligation on injured and adjacent dorsal root ganglion neurons in rats. Anesthesiology 2005, 103:360-376.
• [44]White MM, Aylwin M: Niflumic and flufenamic acids are potent reversible blockers of Ca 2+ -activated Cl − channels in Xenopus oocytes. Mol Pharmacol 1990, 37:720-724.
• [45]Wu G, Hamill OP: NPPB block of Ca 2+ -activated Cl − currents in Xenopus oocytes. Pflugers Arch 1992, 420:227-229.
• [46]Qu Z, Hartzell HC: Functional geometry of the permeation pathway of Ca 2+ -activated Cl − channels inferred from analysis of voltage-dependent block. J Biol Chem 2001, 276:18423-18429.
• [47]Oh SJ, Park JH, Han S, Lee JK, Roh EJ, Lee CJ: Development of selective blockers for Ca 2+ -activated Cl channel using Xenopus laevis oocytes with an improved drug screening strategy. Mol Brain 2008, 1:14. BioMed Central Full Text
• [48]Xu WX, Kim SJ, So I, Kang TM, Rhee JC, Kim KW: Volume-sensitive chloride current activated by hyposmotic swelling in antral gastric myocytes of the guinea-pig. Pflugers Arch 1997, 435:9-19.
• [49]Wang HS, Dixon JE, McKinnon D: Unexpected and differential effects of Cl − channel blockers on the Kv4.3 and Kv4.2 K + channels. Implications for the study of the I(to2) current. Circ Res 1997, 81:711-718.
• [50]Namkung W, Thiagarajah JR, Phuan PW, Verkman AS: Inhibition of Ca 2+ -activated Cl − channels by gallotannins as a possible molecular basis for health benefits of red wine and green tea. FASEB J 2010, 24:4178-4186.
• [51]Liu Y, Zhang H, Huang D, Qi J, Xu J, Gao H: Characterization of the effects of Cl − channel modulators on TMEM16A and bestrophin-1 Ca 2+ activated Cl − channels. Pflugers Arch 2010, 467:1417-1430.
• [52]De La Fuente R, Namkung W, Mills A, Verkman AS: Small-molecule screen identifies inhibitors of a human intestinal calcium-activated chloride channel. Mol Pharmacol 2008, 73:758-768.
• [53]Currie KP, Wootton JF, Scott RH: Activation of Ca 2+ -dependent Cl − currents in cultured rat sensory neurones by flash photolysis of DM-nitrophen. J Physiol 1995, 482(Pt 2):291-307.