Voltage‐gated sodium channel 1.7 expression decreases in dorsal root ganglia in a spinal nerve ligation neuropathic pain model

Abstract

The role of the voltage-gated sodium channel 1.7 (Nav1.7) is unclear in models of neuropathic pain induced by nerve injury. In the present study, we measured expression levels of Nav1.7 in two distinct neuropathic pain models: spinal nerve ligation (SNL) and chronic constriction injury (CCI). In the SNL model, both mRNA and protein levels of Nav1.7 were markedly lower in the L5 dorsal root ganglia (DRG) but were significantly higher in the L4 DRG. Nav1.7 protein levels were notably higher in both L4 and L5 DRGs under CCI conditions. We found that excessive damage of L5 nerves such as SNL reduced expression levels of Nav1.7 in the injured L5 DRG and activated the adjacent uninjured DRG, resulting in Nav1.7 level increases in the adjacent L4 DRG. We confirmed again that Nav1.7 was closely related to neuropathic pain induced by nerve injury. More importantly, our results suggest that tracing the molecular changes exclusively in the L5 DRG in SNL model may not completely explain the pain mechanism; it is necessary to study the adjacent uninjured L4 DRG. K E Y W O R D S chronic constriction injury, dorsal root ganglia, neuropathic pain, spinal nerve ligation, voltagegated sodium channel 1.7

Activating Sirt1 by resveratrol suppresses Nav1.7 expression in DRG through miR-182 and alleviates neuropathic pain in rats

“…Also Nav1.7 is illustrated to play important roles in the development of neuropathic pain. Nav1.7 protein levels were notably increased in L4-L5 DRGs under CCI conditions and is suggested to be one promising effector protein correlated with pathogenesis of neuropathic pain [13]. Considering that miR-182 is the downstream effector of Sirt1 and miR-182 downregulates Nav1.7 expression to relive neuropathic pain in a previous study [14], we hypothesized that Sirt1 might downregulated Nav1.7 expression via miR-182.…”

“…The downstream effector and pathway after resveratrol-initiated Sirt1 activation hasn't been well elucidated. Considering miR-182 is the downstream effector of Sirt1 and miR-182 is reported to decrease Nav1.7 expression, one promising effector protein of neuropathic pain [13], to relive symptoms related with neuropathic pain [14], we hypothesized that Sirt1 might downregulated Nav1.7 expression via miR-182.…”

Tetrodotoxin, a Potential Drug for Neuropathic and Cancer Pain Relief?

“…This VGSC is predominantly localized in the peripheral nervous system, and many studies have reported a strong correlation between Na V 1.7 function and many pain states in rodents and humans [ 20 ]. However, the role of Na V 1.7 in neuropathic pain remains uncertain, as contradictory results have been reported in rodents and humans, with some studies showing upregulation [ 27 , 34 , 40 , 41 , 45 ], and others downregulation [ 24 , 28 , 39 ] in primary sensory neurons. In addition, mice lacking Na V 1.7 normally developed neuropathic pain after peripheral nerve injury [ 48 ].…”

Revisiting PNS Plasticity: How Uninjured Sensory Afferents Promote Neuropathic Pain

“…Both Nav1.7 and Nav1.8 channels can contribute to nociceptor activity and have been implicated in pain syndromes in humans (McDermott et al, 2019). After SNL, uninjured neurons show an increase in mRNA and protein levels of Nav1.7 and Nav1.8 thought to contribute increases in spontaneous activity (Zhang et al, 2004;Li et al, 2019). While other studies have reported no change in Nav1.7 at the level of mRNA after SNL (Fukuoka et al, 2012), a decrease in Nav1.7 protein and mRNA expression has been reported in injured neurons (Li et al, 2019).…”

“…After SNL, uninjured neurons show an increase in mRNA and protein levels of Nav1.7 and Nav1.8 thought to contribute increases in spontaneous activity (Zhang et al, 2004;Li et al, 2019). While other studies have reported no change in Nav1.7 at the level of mRNA after SNL (Fukuoka et al, 2012), a decrease in Nav1.7 protein and mRNA expression has been reported in injured neurons (Li et al, 2019). After L6 SNL in monkey, injured and uninjured C-fibers showed increased spontaneous activity along with increased α-adrenergic sensitivity in uninjured nerve fibers (Ali et al, 1999).…”