The Effects of TNF‐α on TTX Resistant Na
            V
            Current in Muscle Dorsal Root Ganglion Neurons after Femoral Artery Occlusion

The responsiveness of sensory neurons to muscle metabolites is altered under the conditions of insufficient limb blood supply in some diseases, such as peripheral artery disease. The purpose of this study was to examine ATP-induced current with activation of purinergic P2X subtypes P2X3 and P2X2/3 in dorsal root ganglion (DRG) neurons of control limbs and limbs with 24 h of femoral artery occlusion using whole cell patch-clamp methods. Also, dual-labeling immunohistochemistry was employed to determine existence of P2X3 expression in DRG neurons of thin-fiber afferents. DRG neurons from 4- to 6-wk-old rats were labeled by injecting the fluorescence tracer DiI into the hindlimb muscles 4–5 days before the recording experiments. Transient (P2X3), mixed (P2X3 and P2X2/3), and sustained (P2X2/3) current responses to α,β-methylene ATP (a P2X receptor agonist) are observed in small and medium DRG neurons, and size distribution of DRG neurons is similar in control and occluded limbs. However, the peak current amplitude of DRG neuron induced by stimulation of P2X3 and/or P2X2/3 is larger in occluded limbs than that in control limbs. Moreover, the percentage of DRG neurons with P2X3 transient currents is greater after arterial occlusion compared with control. In addition, a rapid desensitization was observed in DRG neurons with transient currents, but not with sustained currents in control and occluded groups. Furthermore, results from immunofluorescence experiments show that femoral artery occlusion primarily augments P2X3 expression within DRG neurons projecting C-fiber afferents. Overall, these findings suggest that 1) greater ATP-induced currents with activation of P2X3 and P2X2/3 are developed when hindlimb arterial blood supply is deficient under ischemic conditions and 2) increased P2X3 expression is largely observed in C-fibers of DRG neurons after hindlimb vascular insufficiency.

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TNF-α-mediated JNK activation in the dorsal root ganglion neurons contributes to Bortezomib-induced peripheral neuropathy

Brain Behavior and Immunity ◽

10.1016/j.bbi.2014.01.020 ◽

2014 ◽

Vol 38 ◽

pp. 185-191 ◽

Cited By ~ 21

Author(s):

Jie Zhang ◽

Yi-Min Su ◽

Dai Li ◽

Yu Cui ◽

Zhen-Zhen Huang ◽

...

Keyword(s):

Peripheral Neuropathy ◽

Dorsal Root Ganglion ◽

Dorsal Root ◽

Dorsal Root Ganglion Neurons ◽

Tnf Α ◽

Ganglion Neurons ◽

Jnk Activation

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Acute P38-Mediated Enhancement of P2X3 Receptor Currents by TNF-α in Rat Dorsal Root Ganglion Neurons

Journal of Inflammation Research ◽

10.2147/jir.s315774 ◽

2021 ◽

Vol Volume 14 ◽

pp. 2841-2850

Author(s):

Ying Jin ◽

Shuang Wei ◽

Ting-Ting Liu ◽

Chun-Yu Qiu ◽

Wang-Ping Hu

Keyword(s):

Dorsal Root Ganglion ◽

Dorsal Root ◽

Dorsal Root Ganglion Neurons ◽

P2x3 Receptor ◽

Tnf Α ◽

Ganglion Neurons

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TNF-α mediated upregulation of NaV1.7 currents in rat dorsal root ganglion neurons is independent of CRMP2 SUMOylation

Molecular Brain ◽

10.1186/s13041-019-0538-0 ◽

2019 ◽

Vol 12 (1) ◽

Cited By ~ 5

Author(s):

Flávio Henrique Pequeno de Macedo ◽

Rosária Dias Aires ◽

Esdras Guedes Fonseca ◽

Renata Cristina Mendes Ferreira ◽

Daniel Portela Dias Machado ◽

...

Keyword(s):

Dorsal Root Ganglion ◽

Diabetic Neuropathy ◽

Dorsal Root ◽

Sodium Current ◽

Dorsal Root Ganglion Neurons ◽

Drg Neurons ◽

Necrosis Factor Alpha ◽

Tnf Α ◽

Ganglion Neurons ◽

Total Sodium

AbstractClinical and preclinical studies have shown that patients with Diabetic Neuropathy Pain (DNP) present with increased tumor necrosis factor alpha (TNF-α) serum concentration, whereas studies with diabetic animals have shown that TNF-α induces an increase in NaV1.7 sodium channel expression. This is expected to result in sensitization of nociceptor neuron terminals, and therefore the development of DNP. For further study of this mechanism, dissociated dorsal root ganglion (DRG) neurons were exposed to TNF-α for 6 h, at a concentration equivalent to that measured in STZ-induced diabetic rats that developed hyperalgesia. Tetrodotoxin sensitive (TTXs), resistant (TTXr) and total sodium current was studied in these DRG neurons. Total sodium current was also studied in DRG neurons expressing the collapsin response mediator protein 2 (CRMP2) SUMO-incompetent mutant protein (CRMP2-K374A), which causes a significant reduction in NaV1.7 membrane cell expression levels. Our results show that TNF-α exposure increased the density of the total, TTXs and TTXr sodium current in DRG neurons. Furthermore, TNF-α shifted the steady state activation and inactivation curves of the total and TTXs sodium current. DRG neurons expressing the CRMP2-K374A mutant also exhibited total sodium current increases after exposure to TNF-α, indicating that these effects were independent of SUMOylation of CRMP2. In conclusion, TNF-α sensitizes DRG neurons via augmentation of whole cell sodium current. This may underlie the pronociceptive effects of TNF-α and suggests a molecular mechanism responsible for pain hypersensitivity in diabetic neuropathy patients.

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Femoral artery occlusion increases expression of ASIC3 in dorsal root ganglion neurons

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00612.2010 ◽

2010 ◽

Vol 299 (5) ◽

pp. H1357-H1364 ◽

Cited By ~ 40

Author(s):

Jiahao Liu ◽

Zhaohui Gao ◽

Jianhua Li

Keyword(s):

Lactic Acid ◽

Dorsal Root Ganglion ◽

Femoral Artery ◽

Dorsal Root ◽

Arterial Occlusion ◽

Sensory Nerves ◽

Dorsal Root Ganglion Neurons ◽

Artery Ligation ◽

Arterial Blood ◽

Ganglion Neurons

Acid-sensing ion channels (ASICs) in sensory nerves are responsive to increases in the levels of protons in the extracellular medium. Prior studies suggest that the muscle metabolite, lactic acid, plays a role in reflex sympathetic and cardiovascular responses via stimulation of thin muscle afferent nerves. Also, femoral artery occlusion augments the reflex sympathetic nerve response in rats. ASIC3 is a main subtype to appear in sensory nerves in mediating the response induced by increases in protons in the interstitial space of contracting muscles. Thus, in this article, we hypothesized that femoral occlusion increases the expression of ASIC3 in primary afferent neurons innervating muscles, and this contributes to the exaggerated reflex sympathetic responses. Femoral occlusion/vascular insufficiency of the hindlimb muscles was induced by the femoral artery ligation in rats. First, Western blot analysis shows that 24–72 h of femoral artery ligation significantly increased the expression of ASIC3 protein in dorsal root ganglion (optical density, 1.0 ± 0.07 in control vs. 1.65 ± 0.1 after 24 h of occlusion, P < 0.05; n = 6 in each group). There were no significant differences for increases in ASIC3 24 and 72 h postocclusion. Second, experiments using fluorescent immunohistochemistry and retrograde-labeling technique show that a greater percentage of ASIC3 staining neurons are localized in muscle-innervating dorsal root ganglion neurons after the arterial occlusion (78 ± 3% in 24 h post occlusion vs. 59 ± 5% in control, P < 0.05; n = 6 in each group). Third, the reflex responses in renal sympathetic nerve and arterial blood pressure induced by the stimulation of ASIC were examined after an injection of lactic acid into the arterial blood supply of hindlimb muscles of control rats and ligated rats. The results demonstrate that the sympathetic and pressor responses to lactic acid were significantly augmented after femoral occlusion compared with those in the control group. The data of this study suggest that enhanced ASIC3 expression in muscle afferent nerves contributes to the exaggerated reflex sympathetic and pressor responses to lactic acid as seen in arterial occlusion.

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