Hyperexcitability and sensitization of sodium channels of dorsal root ganglion neurons in a rat model of lumber disc herniation

Yan, Jun; Zou, Kang; Liu, Xiaofeng; Hu, Shu‐Fen; Wang, Qianliang; Miao, Xiuhua; Zhou, Youlang; Xu, Guang–Yin

doi:10.1007/s00586-015-4171-z

Cited by 19 publications

(22 citation statements)

References 31 publications

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“…Nav1.7 and Nav1.8 expression are also significantly increased in the lumber disc herniation model [52]. Nav1.3 is upregulated in the DRG after nerve injury, in line with the data showing that knockdown of Nav1.3 reduces pain in the neuropathic pain model [53, 54].…”

Section: Mechanism Of Neuropathic Painsupporting

confidence: 58%

Food-Derived Natural Compounds for Pain Relief in Neuropathic Pain

Lim

Kim

2016

BioMed Research International

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Neuropathic pain, defined as pain caused by a lesion or disease of the somatosensory nervous system, is characterized by dysesthesia, hyperalgesia, and allodynia. The number of patients with this type of pain has increased rapidly in recent years. Yet, available neuropathic pain medicines have undesired side effects, such as tolerance and physical dependence, and do not fully alleviate the pain. The mechanisms of neuropathic pain are still not fully understood. Injury causes inflammation and immune responses and changed expression and activity of receptors and ion channels in peripheral nerve terminals. Additionally, neuroinflammation is a known factor in the development and maintenance of neuropathic pain. During neuropathic pain development, the C-C motif chemokine receptor 2 (CCR2) acts as an important signaling mediator. Traditional plant treatments have been used throughout the world for treating diseases. We and others have identified food-derived compounds that alleviate neuropathic pain. Here, we review the natural compounds for neuropathic pain relief, their mechanisms of action, and the potential benefits of natural compounds with antagonistic effects on GPCRs, especially those containing CCR2, for neuropathic pain treatment.

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Section: Mechanism Of Neuropathic Painsupporting

confidence: 58%

Food-Derived Natural Compounds for Pain Relief in Neuropathic Pain

Lim

Kim

2016

BioMed Research International

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“…DRG neurons predominantly express Na V 1.7, Na V 1.8 and Na V 1.910. We have previously showed that VGSCs in DRG neurons were sensitized in this setting11. However, the detailed mechanism underlying the sensitization of VGSCs remains unknown.…”

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confidence: 96%

Inhibition of cystathionine β-synthetase suppresses sodium channel activities of dorsal root ganglion neurons of rats with lumbar disc herniation

Yan

Zou

et al. 2016

Sci Rep

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The pathogenesis of pain in lumbar disc herniation (LDH) remains poorly understood. We have recently demonstrated that voltage-gated sodium channels (VGSCs) in dorsal root ganglion (DRG) neurons were sensitized in a rat model of LDH. However, the detailed molecular mechanism for sensitization of VGSCs remains largely unknown. This study was designed to examine roles of the endogenous hydrogen sulfide synthesizing enzyme cystathionine β-synthetase (CBS) in sensitization of VGSCs in a previously validated rat model of LDH. Here we showed that inhibition of CBS activity by O-(Carboxymethyl) hydroxylamine hemihydrochloride (AOAA) significantly attenuated pain hypersensitivity in LDH rats. Administration of AOAA also reduced neuronal hyperexcitability, suppressed the sodium current density, and right-shifted the V1/2 of the inactivation curve, of hindpaw innervating DRG neurons, which is retrogradely labeled by DiI. In vitro incubation of AOAA did not alter the excitability of acutely isolated DRG neurons. Furthermore, CBS was colocalized with NaV1.7 and NaV1.8 in hindpaw-innervating DRG neurons. Treatment of AOAA markedly suppressed expression of NaV1.7 and NaV1.8 in DRGs of LDH rats. These data suggest that targeting the CBS-H2S signaling at the DRG level might represent a novel therapeutic strategy for chronic pain relief in patients with LDH.

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“…The possible mechanisms included but not excluded the phosphorylation of sodium channels and enhanced trafficking of sodium channels from the cytoplasm to the cell surface membrane. 20 In the present study, although CORT did not alter t in , it significantly reduced Ta of sodium currents. This result suggests that CORT-induced enhancement of sodium current density may not because of aggregation of sodium channel on cell membrane, but at least in part because of changes in channel kinetics.…”

Section: Discussionmentioning

confidence: 59%

“…19 Very recent studies indicated PKC activation leads to an increase in the membrane expression of VGSCs and facilitates sodium currents in cortical neurons, 20,21 indicating that PKC may be involved in mediating VGSCs functions. However, whether and how CORT plays an acute effect on VGSCs of DRG neurons innervating the stomach is not clear.…”

Section: Introductionmentioning

confidence: 99%

Protein Kinase C Mediates the Corticosterone-induced Sensitization of Dorsal Root Ganglion Neurons Innervating the Rat Stomach

Lü

Wang

et al. 2017

J Neurogastroenterol Motil

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Background/AimsGastric hypersensitivity contributes to abdominal pain in patients with functional dyspepsia. Recent studies showed that hormones induced by stress are correlated with visceral hypersensitivity. However, the precise mechanisms underlying gastric hypersensitivity remain largely unknown. The aim of the present study was designed to investigate the roles of corticosterone (CORT) on excitability of dorsal root ganglion (DRG) neurons innervating the stomach. MethodsDRG neurons innervating the stomach were labeled by DiI injection into the stomach wall. Patch clamp recordings were employed to examine neural excitability and voltage-gated sodium channel currents. Electromyograph technique was used to determine the responses of neck muscles to gastric distension. ResultsIncubation of acutely isolated DRG neurons with CORT significantly depolarized action potential threshold and enhanced the number of action potentials induced by current stimulation of the neuron. Under voltage-clamp mode, incubation of CORT enhanced voltagegated sodium current density of the recorded neurons. Pre-incubation of GF109203X, an inhibitor of protein kinase C, blocked the CORT-induced hyperexcitability and potentiation of sodium currents. However, pre-incubation of H-89, an inhibitor of protein kinase A, did not alter the sodium current density. More importantly, intraperitoneal injection of CORT produced gastric hypersensitivity of healthy rats, which was blocked by pre-administration of GF109203X but not H-89. ConclusionsOur data strongly suggest that CORT rapidly enhanced neuronal excitability and sodium channel functions, which is most likely mediated by protein kinase C but not protein kinase A signaling pathway in DRG neurons innervating the stomach, thus underlying the gastric hypersensitivity induced by CORT injection.

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Hyperexcitability and sensitization of sodium channels of dorsal root ganglion neurons in a rat model of lumber disc herniation

Abstract: These data suggest that NP application produces pain-related behavior and potentiates sodium current density of DRG neurons, which is most likely mediated by enhanced expression of NaV1.7 and NaV1.8.

Cited by 19 publications

References 31 publications

Food-Derived Natural Compounds for Pain Relief in Neuropathic Pain

Food-Derived Natural Compounds for Pain Relief in Neuropathic Pain

Inhibition of cystathionine β-synthetase suppresses sodium channel activities of dorsal root ganglion neurons of rats with lumbar disc herniation

Protein Kinase C Mediates the Corticosterone-induced Sensitization of Dorsal Root Ganglion Neurons Innervating the Rat Stomach

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