Highlights
- •Spinal L5 nerve transection up-regulates bestrophin-1 and GAP43 expression in DRG.
- •Spinal nerve ligation (L5/L6) enhanced GAP43 but not bestrophin-1 expression in DRG.
- •SNT increased bestrophin-1 immunoreactivity in CGRP but not in IB4 DRG.
- •Bestrophin-1 recombinant channel injected in naïve rats induced tactile allodynia.
Abstract
Previous studies have reported that L5/L6 spinal nerve ligation (SNL), but not L5
spinal nerve transection (SNT), enhances anoctamin-1 in injured and uninjured dorsal
root ganglia (DRG) of rats suggesting some differences in function of the type of
nerve injury. The role of bestrophin-1 in these conditions is unknown. The aim of
this study was to investigate the role of bestrophin-1 in rats subjected to L5 SNT
and L5/L6 SNL. SNT up-regulated bestrophin-1 protein expression in injured L5 and
uninjured L4 DRG at day 7, whereas it enhanced GAP43 mainly in injured, but also in
uninjured DRG. In contrast, SNL enhanced GAP43 at day 1 and 7, while bestrophin-1
expression increased only at day 1 after nerve injury. Accordingly, intrathecal injection
of the bestrophin-1 blocker CaCCinh-A01 (1-10 µg) reverted SNT- or SNL-induced tactile allodynia in a concentration-dependent
manner. Intrathecal injection of CaCCinh-A01 (10 µg) prevented SNT-induced upregulation of bestrophin-1 and GAP43 at day 7. In
contrast, CaCCinh-A01 did not affect SNL-induced up-regulation of GAP43 nor bestrophin-1. Bestrophin-1
was mainly expressed in small- and medium-size neurons in naïve rats, while SNT increased
bestrophin-1 immunoreactivity in CGRP+, but not in IB4+ neuronal cells in DRG. Intrathecal
injection of bestrophin-1 plasmid (pCMVBest) induced tactile allodynia and increased
bestrophin-1 expression in DRG and spinal cord in naïve rats. CaCCinh-A01 reversed bestrophin-1 overexpression-induced tactile allodynia and restored bestrophin-1
expression. Our data suggest that bestrophin-1 plays a relevant role in neuropathic
pain induced by SNT, but not by SNL.
Perspective
SNT, but not SNL, up-regulates bestrophin-1 and GAP43 protein expression in injured
L5 and uninjured L4 DRG. SNT increases bestrophin-1 immunoreactivity in CGRP+ neurons
in DRG. Bestrophin-1 overexpression induces allodynia. CaCCinh-A01 reduces allodynia
and restores bestrophin-1 expression. Our data suggest bestrophin-1 is differentially
regulated depending on the neuropathic pain model.
Key words
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Article info
Publication history
Published online: December 12, 2022
Accepted:
December 7,
2022
Received in revised form:
November 21,
2022
Received:
May 16,
2022
Publication stage
In Press Journal Pre-ProofFootnotes
Partially supported by Conacyt (Grant A1-S-40015 to VG-S) and SEP-Cinvestav (Grants 129 to VG-S and 269 to JM).
The authors have no conflicts of interest to declare.
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© 2022 by United States Association for the Study of Pain, Inc.
