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

Pineda-Farias JB, Barragán-Iglesias P, Loeza-Alcocer E, Torres-López JE, Rocha-González HI, Pérez-Severiano F, Delgado-Lezama R, Granados-Soto V - Mol Pain (2015)

Bottom Line: Intrathecal administration of non-selective CaCCs inhibitors (NPPB, 9-AC and NFA) dose-dependently reduced tactile allodynia.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.

View Article: PubMed Central - PubMed

Affiliation: 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, 14330, México, D.F., México. jorgepinedafarias@yahoo.com.mx.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

Illustration of the preparation and the compound action potential (CAP). aLeft panel the L5 ganglion attached to dorsal root (DR) and spinal nerve was removed of naïve, sham and neuropathic rats. Right panel the tissue was collocated into a recording chamber. The spinal nerve was stimulated at 50xT to evoke maximal C fiber CAP recorded in the dorsal root. bUpper panel examples of maximal C fiber CAP recorded extracellularly from naïve (black trace), sham and neuropathic (red trace) rats. The bar chart in the lower panel shows the comparison of CAP. Note that the size of the CAP in neuropathic was higher than in naïve rats.
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Fig8: Illustration of the preparation and the compound action potential (CAP). aLeft panel the L5 ganglion attached to dorsal root (DR) and spinal nerve was removed of naïve, sham and neuropathic rats. Right panel the tissue was collocated into a recording chamber. The spinal nerve was stimulated at 50xT to evoke maximal C fiber CAP recorded in the dorsal root. bUpper panel examples of maximal C fiber CAP recorded extracellularly from naïve (black trace), sham and neuropathic (red trace) rats. The bar chart in the lower panel shows the comparison of CAP. Note that the size of the CAP in neuropathic was higher than in naïve rats.

Mentions: In previous studies of mammalian DRG neurons using sharp or patch microelectrodes, action potential duration tended to increase after axotomy [43]. Here, we recorded the C component of the CAP in the dorsal root attached to its ganglion after peripheral stimulation at the spinal nerves (Figure 8a). Area under the curve of the C component of the CAP recorded in neuropathic rats increased in comparison to naïve or sham-operated rats (Figure 8b). Moreover, its conduction velocity was slowed (data not shown).Figure 7


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

Pineda-Farias JB, Barragán-Iglesias P, Loeza-Alcocer E, Torres-López JE, Rocha-González HI, Pérez-Severiano F, Delgado-Lezama R, Granados-Soto V - Mol Pain (2015)

Illustration of the preparation and the compound action potential (CAP). aLeft panel the L5 ganglion attached to dorsal root (DR) and spinal nerve was removed of naïve, sham and neuropathic rats. Right panel the tissue was collocated into a recording chamber. The spinal nerve was stimulated at 50xT to evoke maximal C fiber CAP recorded in the dorsal root. bUpper panel examples of maximal C fiber CAP recorded extracellularly from naïve (black trace), sham and neuropathic (red trace) rats. The bar chart in the lower panel shows the comparison of CAP. Note that the size of the CAP in neuropathic was higher than in naïve rats.
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4487556&req=5

Fig8: Illustration of the preparation and the compound action potential (CAP). aLeft panel the L5 ganglion attached to dorsal root (DR) and spinal nerve was removed of naïve, sham and neuropathic rats. Right panel the tissue was collocated into a recording chamber. The spinal nerve was stimulated at 50xT to evoke maximal C fiber CAP recorded in the dorsal root. bUpper panel examples of maximal C fiber CAP recorded extracellularly from naïve (black trace), sham and neuropathic (red trace) rats. The bar chart in the lower panel shows the comparison of CAP. Note that the size of the CAP in neuropathic was higher than in naïve rats.
Mentions: In previous studies of mammalian DRG neurons using sharp or patch microelectrodes, action potential duration tended to increase after axotomy [43]. Here, we recorded the C component of the CAP in the dorsal root attached to its ganglion after peripheral stimulation at the spinal nerves (Figure 8a). Area under the curve of the C component of the CAP recorded in neuropathic rats increased in comparison to naïve or sham-operated rats (Figure 8b). Moreover, its conduction velocity was slowed (data not shown).Figure 7

Bottom Line: Intrathecal administration of non-selective CaCCs inhibitors (NPPB, 9-AC and NFA) dose-dependently reduced tactile allodynia.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.

View Article: PubMed Central - PubMed

Affiliation: 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, 14330, México, D.F., México. jorgepinedafarias@yahoo.com.mx.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus