scholarly journals Development of Heat Hyperalgesia and Changes of TRPV1 and NGF Expression in Rat Dorsal Root Ganglion Following Joint Immobilization

2013 ◽  
pp. 215-219 ◽  
Author(s):  
T. NISHIGAMI ◽  
Y. OSAKO ◽  
M. IKEUCHI ◽  
K. YURI ◽  
T. USHIDA
Keyword(s):  
Dorsal Root Ganglion ◽  
Dorsal Root ◽  
Transient Receptor Potential ◽  
Wrist Joint ◽  
Receptor Potential ◽  
Phenotypic Change ◽  
Drg Neurons ◽  
Limb Immobilization ◽  
Heat Hyperalgesia

The aim of this study was to examine whether threshold to heat stimuli, and expression of transient receptor potential vanilloid1 (TRPV1) and nerve growth factor (NGF) in dorsal root ganglion (DRG) altered under conditions of long-term limb immobilization. A plastic cast was wrapped around the right limb from the forearm to the forepaw to keep wrist joint at 90° of flexion for 5 weeks. Heat hyperalgesia was tested using the plantar test at 6 h after removing cast. The rats were perfused transcardially with 4 % paraformaldehyde and DRGs were excised at 24 h after removing cast. For size distributions of the TRPV1-IR and NGF-IR neuronal profile, the DRG area measurements over 1000 DRG neurons per animal were measured in each side, on both the immobilized (ipsilateral) and contralateral sides. Ipsilateral withdrawal latency was significantly shorter than contralateral sides. Ipsilateral percentage of immunoreactive neurons in the total DRG neurons was significantly higher than contralateral sides in TRPV1-IR and NGF-IR. Long-term casting induced heat hyperalgesia, and up-regulation and phenotypic change of TRPV1-IR and NGF-IR in DRGs on the immobilized side. These DRG alterations may involve heat hyperalgesia after long-term limb immobilization.

scholarly journals Long-Term Diabetic Microenvironment Augments the Decay Rate of Capsaicin-Induced Currents in Mouse Dorsal Root Ganglion Neurons

Molecules ◽  
2019 ◽  
Vol 24 (4) ◽  
pp. 775
Author(s):  
Xingjuan Chen ◽  
Yaqian Duan ◽  
Ashley Riley ◽  
Megan Welch ◽  
Fletcher White ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Dorsal Root Ganglion ◽  
Patch Clamp ◽  
Dorsal Root ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Dorsal Root Ganglion Neurons ◽  
Transient Receptor Potential Vanilloid ◽  
Drg Neurons ◽  
Ganglion Neurons

Individuals with end-stage diabetic peripheral neuropathy present with decreased pain sensation. Transient receptor potential vanilloid type 1 (TRPV1) is implicated in pain signaling and resides on sensory dorsal root ganglion (DRG) neurons. We investigated the expression and functional activity of TRPV1 in DRG neurons of the Ins2+/Akita mouse at 9 months of diabetes using immunohistochemistry, live single cell calcium imaging, and whole-cell patch-clamp electrophysiology. 2′,7′-Dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescence assay was used to determine the level of Reactive Oxygen Species (ROS) in DRGs. Although TRPV1 expressing neuron percentage was increased in Ins2+/Akita DRGs at 9 months of diabetes compared to control, capsaicin-induced Ca2+ influx was smaller in isolated Ins2+/Akita DRG neurons, indicating impaired TRPV1 function. Consistently, capsaicin-induced Ca2+ influx was decreased in control DRG neurons cultured in the presence of 25 mM glucose for seven days versus those cultured with 5.5 mM glucose. The high glucose environment increased cytoplasmic ROS accumulation in cultured DRG neurons. Patch-clamp recordings revealed that capsaicin-activated currents decayed faster in isolated Ins2+/Akita DRG neurons as compared to those in control neurons. We propose that in poorly controlled diabetes, the accelerated rate of capsaicin-sensitive TRPV1 current decay in DRG neurons decreases overall TRPV1 activity and contributes to peripheral neuropathy.

scholarly journals Intracellular TRPA1 mediates Ca2+ release from lysosomes in dorsal root ganglion neurons

2016 ◽  
Vol 215 (3) ◽  
pp. 369-381 ◽  
Author(s):  
Shujiang Shang ◽  
Feipeng Zhu ◽  
Bin Liu ◽  
Zuying Chai ◽  
Qihui Wu ◽  
...  
Keyword(s):  
Dorsal Root Ganglion ◽  
Dorsal Root ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Allyl Isothiocyanate ◽  
Dorsal Root Ganglion Neurons ◽  
Drg Neurons ◽  
Vesicle Exocytosis ◽  
Transient Receptor ◽  
Ganglion Neurons

Transient receptor potential A1 (TRPA1) is a nonselective cation channel implicated in thermosensation and inflammatory pain. In this study, we show that TRPA1 (activated by allyl isothiocyanate, acrolein, and 4-hydroxynonenal) elevates the intracellular Ca2+ concentration ([Ca2+]i) in dorsal root ganglion (DRG) neurons in the presence and absence of extracellular Ca2+. Pharmacological and immunocytochemical analyses revealed the presence of TRPA1 channels both on the plasma membrane and in endolysosomes. Confocal line-scan imaging demonstrated Ca2+ signals elicited from individual endolysosomes (“lysosome Ca2+ sparks”) by TRPA1 activation. In physiological solutions, the TRPA1-mediated endolysosomal Ca2+ release contributed to ∼40% of the overall [Ca2+]i rise and directly triggered vesicle exocytosis and calcitonin gene-related peptide release, which greatly enhanced the excitability of DRG neurons. Thus, in addition to working via Ca2+ influx, TRPA1 channels trigger vesicle release in sensory neurons by releasing Ca2+ from lysosome-like organelles.

scholarly journals Nogo-A Induced Polymerization of Microtubule Is Involved in the Inflammatory Heat Hyperalgesia in Rat Dorsal Root Ganglion Neurons

2021 ◽  
Vol 22 (19) ◽  
pp. 10360
Author(s):  
Ling Chen ◽  
Qiguo Hu ◽  
Huaicun Liu ◽  
Yan Zhao ◽  
Sun-On Chan ◽  
...  
Keyword(s):  
Dorsal Root Ganglion ◽  
Inflammatory Pain ◽  
Dorsal Root ◽  
Intrathecal Injection ◽  
Dorsal Root Ganglion Neurons ◽  
Microtubule Assembly ◽  
Major Constituent ◽  
Drg Neurons ◽  
Ganglion Neurons ◽  
Heat Hyperalgesia

The microtubule, a major constituent of cytoskeletons, was shown to bind and interact with transient receptor potential vanilloid subfamily member 1 (TRPV1), and serves a pivotal role to produce thermal hyperalgesia in inflammatory pain. Nogo-A is a modulator of microtubule assembly and plays a key role in maintaining the function of TRPV1 in inflammatory heat pain. However, whether the microtubule dynamics modulated by Nogo-A in dorsal root ganglion (DRG) neurons participate in the inflammatory pain is not elucidated. Here we reported that the polymerization of microtubules in the DRG neurons, as indicated by the acetylated α-tubulin, tubulin polymerization-promoting protein 3 (TPPP3), and microtubule numbers, was significantly elevated in the complete Freund’s adjuvant (CFA) induced inflammatory pain. Consistent with our previous results, knock-out (KO) of Nogo-A protein significantly attenuated the heat hyperalgesia 72 h after CFA injection and decreased the microtubule polymerization via up-regulation of phosphorylation of collapsin response mediator protein 2 (CRMP2) in DRG. The colocalization of acetylated α-tubulin and TRPV1 in DRG neurons was also reduced dramatically in Nogo-A KO rats under inflammatory pain. Moreover, the down-regulation of TRPV1 in DRG of Nogo-A KO rats after injection of CFA was reversed by intrathecal injection of paclitaxel, a microtubule stabilizer. Furthermore, intrathecal injection of nocodazole (a microtubule disruptor) attenuated significantly the CFA-induced inflammatory heat hyperalgesia and the mechanical pain in a rat model of spared nerve injury (SNI). In these SNI cases, the Nogo-A and acetylated α-tubulin in DRG were also significantly up-regulated. We conclude that the polymerization of microtubules promoted by Nogo-A in DRG contributes to the development of inflammatory heat hyperalgesia mediated by TRPV1.

Effect of paclitaxel on transient receptor potential vanilloid 1 in rat dorsal root ganglion

Pain ◽  
2013 ◽  
Vol 154 (6) ◽  
pp. 882-889 ◽  
Author(s):  
Tomomi Hara ◽  
Terumasa Chiba ◽  
Kenji Abe ◽  
Akiko Makabe ◽  
Souichi Ikeno ◽  
...  
Keyword(s):  
Dorsal Root Ganglion ◽  
Dorsal Root ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Transient Receptor
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