Bestrophin-1 Participates in Neuropathic Pain Induced by Spinal Nerve Transection but not Spinal Nerve Ligation

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 mg) reverted SNT-or SNL-induced tactile allodynia in a concentration-dependent manner. Intra-thecal injection of CaCCinh-A01 (10 mg) 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 bestro-phin-1. Bestrophin-1 was mainly expressed in small-and medium-size neurons in naieurove rats, while SNT increased bestrophin-1 immunoreactivity in CGRP+, but not in IB4+ neuronal cells in DRG. Intra-thecal injection of bestrophin-1 plasmid (pCMVBest) induced tactile allodynia and increased bestro-phin-1 expression in DRG and spinal cord in naieurove 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 bestro-phin-1 expression. Our data suggest bestrophin-1 is differentially regulated depending on the neuro-pathic pain model.(c) 2022 by United States Association for the Study of Pain, Inc.

Automated summary

Previous studies have shown that L5/L6 spinal nerve ligation enhances the expression of anoctamin-1 in injured and uninjured dorsal root ganglia (DRG), while L5 spinal nerve transection does not. The role of bestrophin-1 in these conditions is still unknown.