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Computational analysis of a 9D model for a small DRG neuron [article]

Parul Verma, Achim Kienle, Dietrich Flockerzi, Doraiswami Ramkrishna
2020 arXiv   pre-print
To this end, we present a numerical bifurcation analysis of a small DRG neuron model in this paper. The model is of Hodgkin-Huxley type and has 9 state variables.  ...  Small dorsal root ganglion (DRG) neurons are primary nociceptors which are responsible for sensing pain. Elucidation of their dynamics is essential for understanding and controlling pain.  ...  Yang Yang, Purdue University, USA, for insightful discussions on DRG neurons and pain sensation.  ... 
arXiv:2001.04915v1 fatcat:ftcydtautbdarhbapmfpq7iq4y

Characteristics of sensory neuronal groups in CGRP-cre-ER reporter mice: Comparison to Nav1.8-cre, TRPV1-cre and TRPV1-GFP mouse lines

Mayur J. Patil, Anahit H. Hovhannisyan, Armen N. Akopian, David D. McKemy
2018 PLoS ONE  
Finally, the described approach for detailed characterization of sensory neuronal groups can be applied to a variety of reporter mice.  ...  To precisely define the function and plasticity of sensory neurons in detail, new tools such as transgenic mouse models are needed.  ...  Michael Henry for guidance on IHC. We are grateful to Dr. Pao-Tien Chuang (UC San Francisco, San Francisco, CA) for kindly providing the CGRP cre/+-ER mouse line; Dr.  ... 
doi:10.1371/journal.pone.0198601 pmid:29864146 pmcid:PMC5986144 fatcat:ymwmyyh66barhce2jcshctggfe

The dorsal root ganglion in Friedreich's ataxia

Arnulf H. Koeppen, Jennifer A. Morral, Ashley N. Davis, Jiang Qian, Simone V. Petrocine, Mitchell D. Knutson, Walter M. Gibson, Matthew J. Cusack, Danhong Li
2009 Acta Neuropathologica  
Many previous authors also emphasized the selective vulnerability of larger neurons in DRG and thicker myelinated DR axons.  ...  antibodies to specific proteins of myelin, neurons and axons; S-100a as a marker of satellite and Schwann cells; laminin; and the iron-responsive proteins ferritin, mitochondrial ferritin, and ferroportin  ...  Acknowledgments The authors express their gratitude to the families of FRDA patients who agreed to donate tissues for research.  ... 
doi:10.1007/s00401-009-0589-x pmid:19727777 fatcat:cyormjobizcjnc6feb5ojtspc4

Inhibition of mechanical allodynia in neuropathic pain by TLR5-mediated A-fiber blockade

Zhen-Zhong Xu, Yong Ho Kim, Sangsu Bang, Yi Zhang, Temugin Berta, Fan Wang, Seog Bae Oh, Ru-Rong Ji
2015 Nature Medicine  
Quantitative analysis demonstrated that 22% and 26% of DRG neurons express Tlr5 and NF200, respectively, and that 20% of DRG neurons are positive for both Tlr5 and NF200.  ...  We also observed Tlr5 mRNA in a small portion of small-diameter neurons (Fig. 1a,c) .  ...  Quantitative analysis demonstrated that 22% and 26% of DRG neurons express Tlr5 and NF200, respectively, and that 20% of DRG neurons are positive for both Tlr5 and NF200.  ... 
doi:10.1038/nm.3978 pmid:26479925 pmcid:PMC4752254 fatcat:5z46dvrjgfcfjj5btzdhsw4bgq

Dysregulation of Kv3.4 Channels in Dorsal Root Ganglia Following Spinal Cord Injury

D. M. Ritter, B. M. Zemel, T. J. Hala, M. E. O'Leary, A. C. Lepore, M. Covarrubias
2015 Journal of Neuroscience  
Furthermore, consistent with Kv3.4 channel dysregulation, PKC activation failed to shorten the AP duration of small-diameter DRG neurons.  ...  Kv3.4 channels are expressed in DRG neurons, where they help regulate action potential (AP) repolarization in a manner that depends on the modulation of inactivation by protein kinase C (PKC)-dependent  ...  noise analysis in naive smalldiameter DRG neurons (Fig. 11 A, B) .  ... 
doi:10.1523/jneurosci.1594-14.2015 pmid:25609640 pmcid:PMC4300326 fatcat:4ciry5vfezcdnbctzhy7piguy4

Discovery of aryl sulfonamide-selective Nav1.7 inhibitors with a highly hydrophobic ethanoanthracene core

Jin-tao Wang, Yue-ming Zheng, Yue-ting Chen, Min Gu, Zhao-bing Gao, Fa-jun Nan
2019 Acta Pharmacologica Sinica  
Preliminary in vivo experiments showed that compound 10o possessed good analgesic activity: in a mouse visceral pain model, administration of compound 10o (30-100 mg/kg, i.p.) effectively and dose-dependently  ...  In mouse small-sized dorsal root ganglion neurons, compound 10o (10, 100 nmol/L) dose-dependently decreased the sodium currents and dramatically suppressed depolarizing current-elicited neuronal discharge  ...  ACKNOWLEDGEMENTS This work was supported by the National Science Fund for Distinguished Young Scholars (81825021) and the National Natural Science Foundation of China (81603096, 81773707).  ... 
doi:10.1038/s41401-019-0267-z pmid:31316182 fatcat:5lpkspc25zbf3jbekpd5nmjwbm

Antinociceptive Effects of AGAP, a Recombinant Neurotoxic Polypeptide: Possible Involvement of the Tetrodotoxin-Resistant Sodium Channels in Small Dorsal Root Ganglia Neurons

Chun-Li Li, Xi-Fang Liu, Gui-Xia Li, Meng-qi Ban, Jian-Zhao Chen, Yong Cui, Jing-Hai Zhang, Chun-Fu Wu
2016 Frontiers in Pharmacology  
Thus, our results demonstrated that submicromolar concentrations of AGAP inhibited TTX-R sodium channel in rat small-diameter DRG neurons.  ...  The results showed that AGAP (3-1000 nM) inhibited the sodium currents in small-diameter DRG neurons in a dosedependent manner. 1000 nM AGAP could inhibit the current density-voltage relationship curve  ...  10 kHz, then sampled data were stored digitally on a computer for further analysis.  ... 
doi:10.3389/fphar.2016.00496 pmid:28066245 pmcid:PMC5168466 fatcat:3gmjudbgxrhvxjrmqms7xvhg6a

Single cell transcriptomics of primate sensory neurons identifies cell types associated with human chronic pain [article]

Jussi Kupari, Dmitry Usoskin, Daohua Lou, Marc Parisien, Yizhou Hu, Michael Fatt, Peter Lonnerberg, Mats Spangberg, Bengt Eriksson, Nikolaos Barkas, Peter Kharchenko, Karin Lore (+3 others)
2020 bioRxiv   pre-print
Identification of primate sensory neuron types is critical for understanding the cellular origin and heritability of chronic pain.  ...  First, we identified cell correlates between two major datasets for mouse sensory neuron types.  ...  Karlsson Hedenstam for donating euthenized animals, Sten Linnarsson for computational support and Eneritz Agirre for help with the Shiny-app and running SCENIC.  ... 
doi:10.1101/2020.12.07.414193 fatcat:3nhpqnjzmffffnq4t5d3725mbq

MBD1 Contributes to the Genesis of Acute Pain and Neuropathic Pain by Epigenetic Silencing of Oprm1 and Kcna2 Genes in Primary Sensory Neurons

Kai Mo, Shaogen Wu, Xiyao Gu, Ming Xiong, Weihua Cai, Fidelis E. Atianjoh, Emily E. Jobe, Xinyu Zhao, Wei-Feng Tu, Yuan-Xiang Tao
2018 Journal of Neuroscience  
We report here that MBD1 in the primary sensory neurons of DRG is critical for the genesis of acute pain and neuropathic pain as DRG MBD1-deficient mice exhibit the reduced responses to acute mechanical  ...  DRG MBD1 is likely a key player under the conditions of acute pain and neuropathic pain.  ...  Our single-cell RT-PCR analysis revealed coexpression of Mbd1 mRNA with Dnmt3a mRNA in individual small, medium, and large DRG neurons (Fig. 9D) .  ... 
doi:10.1523/jneurosci.0880-18.2018 fatcat:y77ebdhd7fbchiwzjv56ukfsmu

DNA methyltransferase DNMT3a contributes to neuropathic pain by repressing Kcna2 in primary afferent neurons

Jian-Yuan Zhao, Lingli Liang, Xiyao Gu, Zhisong Li, Shaogen Wu, Linlin Sun, Fidelis E. Atianjoh, Jian Feng, Kai Mo, Shushan Jia, Brianna Marie Lutz, Alex Bekker (+2 others)
2017 Nature Communications  
Here, we report that peripheral nerve injury increases expression of the DNA methyltransferase DNMT3a in the injured DRG neurons via the activation of the transcription factor octamer transcription factor  ...  Conversely, in the absence of nerve injury, mimicking this increase reduces the Kcna2 promoter activity, diminishes Kcna2 expression, decreases Kv current, increases excitability in DRG neurons and leads  ...  Single-cell RT-PCR analysis revealed co-expression of Oct1 mRNA with Dnmt3a mRNA in individual small, medium or large DRG neurons (Fig. 3g) .  ... 
doi:10.1038/ncomms14712 pmid:28270689 pmcid:PMC5344974 fatcat:pgjb3b6s3rddjcgd2foitkffnm

Population Coding of Forelimb Joint Kinematics by Peripheral Afferents in Monkeys

Tatsuya Umeda, Kazuhiko Seki, Masa-aki Sato, Yukio Nishimura, Mitsuo Kawato, Tadashi Isa, Paul L. Gribble
2012 PLoS ONE  
In this study, we obtained multichannel recordings from dorsal root ganglion (DRG) neurons in cervical segments of monkeys.  ...  Using the SLiR algorithm, we reconstructed the temporal changes of joint angle, angular velocity, and acceleration at the elbow, wrist, and finger joints from temporal firing patterns of the DRG neurons  ...  Sakatani for technical support in operating the motion capture system. Author Contributions  ... 
doi:10.1371/journal.pone.0047749 pmid:23112841 pmcid:PMC3480417 fatcat:re5n3w73ovd5pbxvzfp3sqlfyu

Experimental and computational evidence for an essential role of NaV1.6 in spike initiation at stretch-sensitive colorectal afferent endings

Bin Feng, Yi Zhu, Jun-Ho La, Zachary P. Wills, G. F. Gebhart
2015 Journal of Neurophysiology  
Computational simulation of a colorectal 37 afferent ending that incorporated independent Markov models for Na V 1.6 and Na V 1.7, 38 respectively, recapitulated the experimental findings, suggesting a  ...  In addition, 40 computational simulation of a DRG soma showed that by adding a Na V 1.6 41 conductance, a single-spiking neuron was converted into a tonic spiking one.  ...  Because 475 experimental studies suggested the absence of Na V 1.6 currents in small-diameter 476 DRG neurons(Cummins et al. 2005), the Na V 1.6 conductance in the c-DRG soma 477 model was set to zero  ... 
doi:10.1152/jn.00717.2014 pmid:25652923 pmcid:PMC4416596 fatcat:idx2v7kbyzcdhflxdyxyza4oly

TRPV1 SUMOylation regulates nociceptive signaling in models of inflammatory pain

Yan Wang, Yingwei Gao, Quan Tian, Qi Deng, Yangbo Wang, Tian Zhou, Qiang Liu, Kaidi Mei, Yingping Wang, Huiqing Liu, Ruining Ma, Yuqiang Ding (+6 others)
2018 Nature Communications  
Although TRPV1 channels represent a key player of noxious heat sensation, the precise mechanisms for thermal hyperalgesia remain unknown.  ...  More importantly, the reduced ability of TRPV1 knockout mice to develop inflammatory thermal hyperalgesia was rescued by viral infection of lumbar 3/4 DRG neurons of wild-type TRPV1, but not its SUMOylation-deficient  ...  T RPV1 is a ligand-gated non-selective cation channel prominently expressed in small-and medium-diameter sensory neurons within dorsal root ganglia (DRG), where it functions as a sensor for an array of  ... 
doi:10.1038/s41467-018-03974-7 pmid:29670121 pmcid:PMC5906468 fatcat:ptswhkab4rbqvkpkmd6324nom4

Trypsin-protease activated receptor-2 signaling contributes to pancreatic cancer pain

Jiao Zhu, Xue-Rong Miao, Kun-Ming Tao, Hai Zhu, Zhi-Yun Liu, Da-Wei Yu, Qian-Bo Chen, Hai-Bo Qiu, Zhi-Jie Lu
2017 OncoTarget  
Supernatants from cultured human pancreatic cancer tissues (PC supernatants) induced substance P and calcitonin gene-related peptide release in dorsal root ganglia (DRG) neurons, and FS-NH 2 , a selective  ...  A BALB/c nude mouse orthotopic tumor model was used to confirm the role of PAR-2 signaling in pancreatic cancer visceral pain, and male Sprague-Dawley rats were used to assess ambulatory pain.  ...  CONFLICTS OF INTEREST The authors declare no conflicts of interest. GRANT SUPPORT  ... 
doi:10.18632/oncotarget.18696 pmid:28977906 pmcid:PMC5617466 fatcat:nkjaja2vdvdq5ej4cs4r5yrwcu

Facilitation of TRPV4 by TRPV1 is required for itch transmission in some sensory neuron populations

S. Kim, D. M. Barry, X.-Y. Liu, S. Yin, A. Munanairi, Q.-T. Meng, W. Cheng, P. Mo, L. Wan, S.-B. Liu, K. Ratnayake, Z.-Q. Zhao (+4 others)
2016 Science Signaling  
TRPV4 is required for serotonin (5-hydroxytryptamine)-induced itch (11), but a role for TRPV4 in sensory neurons responding to histamine has not been reported.  ...  TRPV1 responds to the itch-inducing endogenous signal histamine, and TRPA1 responds to the § Although more than a dozen TRPs have been identified in DRG neurons (10), to date, only TRPV1, TRPA1, and TRPV4  ...  Story for Trpa1 −/− and Trpv1 −/− mice, A. Patapoutian for TRPA1 antibody, X. Dong and Q. Liu for Pirt-GCaMP3 mice, J. Yin for technical support, and the members of Chen's laboratory for comments.  ... 
doi:10.1126/scisignal.aaf1047 pmid:27436359 pmcid:PMC5310287 fatcat:mrbi4ffvxvflndujogiuejoidu
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