Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Experimental and Therapeutic Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-0981 Online ISSN: 1792-1015
Journal Cover
March-2017 Volume 13 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
March-2017 Volume 13 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

Impact of gabapentin on neuronal high voltage‑activated Ca2+ channel properties of injured‑side axotomized and adjacent uninjured dorsal root ganglions in a rat model of spinal nerve ligation

  • Authors:
    • Minmin Zhu
    • Xiaodi Sun
    • Xiaodong Chen
    • Hang Xiao
    • Manlin Duan
    • Jianguo Xu
  • View Affiliations / Copyright

    Affiliations: Department of Anaesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, Jiangsu 210002, P.R. China, Department of Anaesthesiology, First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210002, P.R. China, Department of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
    Copyright: © Zhu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 851-860
    |
    Published online on: January 20, 2017
       https://doi.org/10.3892/etm.2017.4071
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

The density and properties of ion channels in the injured axon and dorsal root ganglion (DRG) neuronal soma membrane change following nerve injury, which may result in the development of neuropathic pain. Gabapentin (GBP) is a drug for the first‑line treatment of neuropathic pain. One of its therapeutic targets is the voltage‑activated calcium channel (VACC). In the present study, the whole‑cell patch clamp technique was used to examine the changes of high voltage-activated Ca2+ (HVA‑Ca2+) channels in DRG neurons from sham and neuropathic rats in the absence and presence of GBP. The results demonstrated a reduction in peak current density and the ‘window current' between activation and inactivation in adjacent and axotomized neurons from rats that had undergone L5 spinal nerve ligation, thus attenuating the total inward Ca2+ current. Following the use of the specific channel blockers nifedipine, ω‑conotoxin MVIIC and ω‑conotoxin MVIIA, increased HVA‑Ca2+ channels as well as an increased proportion of N‑type Ca2+ currents were observed in axotomized neurons. GBP inhibited HVA calcium channel currents in a dose‑dependent manner. The activation and steady‑state inactivation curves for HVA channels were shifted in a hyperpolarizing direction by 100 µmol/l GBP. Following the application of GBP, a reduction in the ‘window current' was observed in control and axotomized neurons, whereas the ‘window current' was unchanged in adjacent neurons. This indicates that the inhibitory effects of GBP may be dependent on particular neuropathological or inflammatory conditions. The proportion of N‑type Ca2+ currents and sensitivity to GBP were increased in axotomized neurons, which indicated the involvement of N‑type Ca2+ currents in the inhibitory effect of GBP.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Costigan M, Scholz J and Woolf CJ: Neuropathic Pain: A maladaptive response of the nervous system to damage. Annu Rev Neurosci. 32:1–32. 2009. View Article : Google Scholar : PubMed/NCBI

2 

Sommer C: Neuropathic pain: Pathophysiology, assessment and therapy. Schmerz. 27:619–632. 2013.(In German). View Article : Google Scholar : PubMed/NCBI

3 

Laedermann CJ, Pertin M, Suter MR and Decosterd I: Voltage-gated sodium channel expression in mouse DRG after SNI leads to re-evaluation of projections of injured fibers. Mol Pain. 10:192014. View Article : Google Scholar : PubMed/NCBI

4 

Tsantoulas C, Zhu L, Shaifta Y, Grist J, Ward JP, Raouf R, Michael GJ and McMahon SB: Sensory neuron downregulation of the Kv9.1 potassium channel subunit mediates neuropathic pain following nerve injury. J Neurosci. 32:17502–17513. 2012. View Article : Google Scholar : PubMed/NCBI

5 

Sapunar D, Ljubkovic M, Lirk P, McCallum JB and Hogan QH: Distinct membrane effects of spinal nerve ligation on injured and adjacent dorsal root ganglion neurons in rats. Anesthesiology. 103:360–376. 2005. View Article : Google Scholar : PubMed/NCBI

6 

Ma C, Shu Y, Zheng Z, Chen Y, Yao H, Greenquist KW, White FA and LaMotte RH: Similar electrophysiological changes in axotomized and neighboring intact dorsal root ganglion neurons. J Neurophysiol. 89:1588–1602. 2003. View Article : Google Scholar : PubMed/NCBI

7 

Zhu YF, Wu Q and Henry JL: Changes in functional properties of A-type but not C-type sensory neurons in vivo in a rat model of peripheral neuropathy. J Pain Res. 5:175–192. 2012.PubMed/NCBI

8 

Felix R, Calderón-Rivera A and Andrade A: Regulation of high-voltage-activated Ca2+ channel function, trafficking, and membrane stability by auxiliary subunits. Wiley Interdiscip Rev Membr Transp Signal. 2:207–220. 2013. View Article : Google Scholar : PubMed/NCBI

9 

Zhou C and Luo ZD: Electrophysiological characterization of spinal neuron sensitization by elevated calcium channel alpha-2-delta-1 subunit protein. Eur J Pain. 18:649–658. 2014. View Article : Google Scholar : PubMed/NCBI

10 

Hooker BA, Tobon G, Baker SJ, Zhu C, Hesterman J, Schmidt K, Rajagovindan R, Chandran P, Joshi SK, Bannon AW, et al: Gabapentin-induced pharmacodynamic effects in the spinal nerve ligation model of neuropathic pain. Eur J Pain. 18:223–237. 2014. View Article : Google Scholar : PubMed/NCBI

11 

Kukkar A, Bali A, Singh N and Jaggi AS: Implications and mechanism of action of gabapentin in neuropathic pain. Arch Pharm Res. 36:237–251. 2013. View Article : Google Scholar : PubMed/NCBI

12 

Kim SH and Chung JM: An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat. Pain. 50:355–363. 1992. View Article : Google Scholar : PubMed/NCBI

13 

Choi Y, Yoon YW, Na HS, Kim SH and Chung JM: Behavioral signs of ongoing pain and cold allodynia in a rat model of neuropathic pain. Pain. 59:369–376. 1994. View Article : Google Scholar : PubMed/NCBI

14 

Harper AA and Lawson SN: Conduction velocity is related to morphological cell type in rat dorsal root ganglion neurons. J Physiol. 359:31–46. 1985. View Article : Google Scholar : PubMed/NCBI

15 

McCallum JB, Kwok WM, Sapunar D, Fuchs A and Hogan QH: Painful peripheral nerve injury decreases calcium current in axotomized sensory neurons. Anesthesiology. 105:160–168. 2006. View Article : Google Scholar : PubMed/NCBI

16 

Hogan QH: Role of decreased sensory neuron membrane calcium currents in the genesis of neuropathic pain. Croat Med J. 48:9–21. 2007.PubMed/NCBI

17 

Baccei ML and Kocsis JD: Voltage-gated calcium currents in axotomized adult rat cutaneous afferent neurons. J Neurophysiol. 83:2227–2238. 2000.PubMed/NCBI

18 

McCallum JB, Kwok WM, Mynlieff M, Bosnjak ZJ and Hogan QH: Loss of T-type calcium current in sensory neurons of rats with neuropathic pain. Anesthesiology. 98:209–216. 2003. View Article : Google Scholar : PubMed/NCBI

19 

Blair NT and Bean BP: Roles of tetrodotoxin (TTX)-sensitive Na+ current, TTX-resistant Na+ current, and Ca2+ current in the action potentials of nociceptive sensory neurons. J Neurosci. 22:10277–10290. 2002.PubMed/NCBI

20 

Lirk P, Poroli M, Rigaud M, Fuchs A, Fillip P, Huang CY, Ljubkovic M, Sapunar D and Hogan Q: Modulators of calcium influx regulate membrane excitability in rat dorsal root ganglion neurons. Anesth Analg. 107:673–685. 2008. View Article : Google Scholar : PubMed/NCBI

21 

Jang JH, Lee BH, Nam TS, Kim JW, Kim DW and Leem JW: Peripheral contributions to the mechanical hyperalgesia following a lumbar 5 spinal nerve lesion in rats. Neuroscience. 165:221–232. 2010. View Article : Google Scholar : PubMed/NCBI

22 

Yang L and Stephens GJ: Effects of neuropathy on high-voltage-activated Ca (2+) current in sensory neurones. Cell Calcium. 46:248–256. 2009. View Article : Google Scholar : PubMed/NCBI

23 

Sun XD, Zhu MM, Chen XD, Li D, Wang Q, Xiao H, Xu JG and Duan ML: Effects of gabapentin on high-voltage-activated calcium current in dorsal root ganglion neurons in rats. Zhonghua Yi Xue Za Zhi. 91:1713–1717. 2011.(In Chinese). PubMed/NCBI

24 

Hogan QH, McCallum JB, Sarantopoulos C, Aason M, Mynlieff M, Kwok WM and Bosnjak ZJ: Painful neuropathy decreases membrane calcium current in mammalian primary afferent neurons. Pain. 86:43–53. 2000. View Article : Google Scholar : PubMed/NCBI

25 

Kim DS, Yoon CH, Lee SJ, Park SY, Yoo HJ and Cho HJ: Changes in voltage-gated calcium channel alpha(1) gene expression in rat dorsal root ganglia following peripheral nerve injury. Brain Res Mol Brain Res. 96:151–156. 2001. View Article : Google Scholar : PubMed/NCBI

26 

Rycroft BK, Vikman KS and Christie MJ: Inflammation reduces the contribution of N-type calcium channels to primary afferent synaptic transmission onto NK1 receptor-positive lamina I neurons in the rat dorsal horn. J Physiol. 580:883–894. 2007. View Article : Google Scholar : PubMed/NCBI

27 

Luo ZD, Calcutt NA, Higuera ES, Valder CR, Song YH, Svensson CI and Myers RR: Injury type-specific calcium channel alpha 2 delta-1 subunit up-regulation in rat neuropathic pain models correlates with antiallodynic effects of gabapentin. J Pharmacol Exp Ther. 303:1199–1205. 2002. View Article : Google Scholar : PubMed/NCBI

28 

Gauchan P, Andoh T, Ikeda K, Fujita M, Sasaki A, Kato A and Kuraishi Y: Mechanical allodynia induced by paclitaxel, oxaliplatin and vincristine: Different effectiveness of gabapentin and different expression of voltage-dependent calcium channel alpha(2)delta-1 subunit. Biol Pharm Bull. 32:732–734. 2009. View Article : Google Scholar : PubMed/NCBI

29 

Gabapentin for Adults with Neuropathic Pain, . A Review of the Clinical Evidence and Guidelines. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health; 2014

30 

Sarantopoulos C, McCallum B, Kwok WM and Hogan Q: Gabapentin decreases membrane calcium currents in injured as well as in control mammalian primary afferent neurons. Reg Anesth Pain Med. 27:47–57. 2002. View Article : Google Scholar : PubMed/NCBI

31 

Sutton KG, Martin DJ, Pinnock RD, Lee K and Scott RH: Gabapentin inhibits high-threshold calcium channel currents in cultured rat dorsal root ganglion neurones. Br J Pharmacol. 135:257–265. 2002. View Article : Google Scholar : PubMed/NCBI

32 

Boroujerdi A, Zeng J, Sharp K, Kim D, Steward O and Luo ZD: Calcium channel alpha-2-delta-1 protein upregulation in dorsal spinal cord mediates spinal cord injury-induced neuropathic pain states. Pain. 152:649–655. 2011. View Article : Google Scholar : PubMed/NCBI

33 

Benedikt Nimmervoll: The function of the Ca2+ channel α2δ subunits in synaptic release in hippocampal neurons.

34 

Lana B, Schlick B, Martin S, Pratt WS, Page KM, Goncalves L, Rahman W, Dickenson AH, Bauer CS and Dolphin AC: Differential upregulation in DRG neurons of an α2δ-1 splice variant with a lower affinity for gabapentin after peripheral sensory nerve injury. Pain. 155:522–533. 2014. View Article : Google Scholar : PubMed/NCBI

35 

Meyer RA and Ringkamp M: A role for uninjured afferents in neuropathic pain. Sheng Li Xue Bao. 60:605–609. 2008.PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Zhu M, Sun X, Chen X, Xiao H, Duan M and Xu J: Impact of gabapentin on neuronal high voltage‑activated Ca2+ channel properties of injured‑side axotomized and adjacent uninjured dorsal root ganglions in a rat model of spinal nerve ligation. Exp Ther Med 13: 851-860, 2017.
APA
Zhu, M., Sun, X., Chen, X., Xiao, H., Duan, M., & Xu, J. (2017). Impact of gabapentin on neuronal high voltage‑activated Ca2+ channel properties of injured‑side axotomized and adjacent uninjured dorsal root ganglions in a rat model of spinal nerve ligation. Experimental and Therapeutic Medicine, 13, 851-860. https://doi.org/10.3892/etm.2017.4071
MLA
Zhu, M., Sun, X., Chen, X., Xiao, H., Duan, M., Xu, J."Impact of gabapentin on neuronal high voltage‑activated Ca2+ channel properties of injured‑side axotomized and adjacent uninjured dorsal root ganglions in a rat model of spinal nerve ligation". Experimental and Therapeutic Medicine 13.3 (2017): 851-860.
Chicago
Zhu, M., Sun, X., Chen, X., Xiao, H., Duan, M., Xu, J."Impact of gabapentin on neuronal high voltage‑activated Ca2+ channel properties of injured‑side axotomized and adjacent uninjured dorsal root ganglions in a rat model of spinal nerve ligation". Experimental and Therapeutic Medicine 13, no. 3 (2017): 851-860. https://doi.org/10.3892/etm.2017.4071
Copy and paste a formatted citation
x
Spandidos Publications style
Zhu M, Sun X, Chen X, Xiao H, Duan M and Xu J: Impact of gabapentin on neuronal high voltage‑activated Ca2+ channel properties of injured‑side axotomized and adjacent uninjured dorsal root ganglions in a rat model of spinal nerve ligation. Exp Ther Med 13: 851-860, 2017.
APA
Zhu, M., Sun, X., Chen, X., Xiao, H., Duan, M., & Xu, J. (2017). Impact of gabapentin on neuronal high voltage‑activated Ca2+ channel properties of injured‑side axotomized and adjacent uninjured dorsal root ganglions in a rat model of spinal nerve ligation. Experimental and Therapeutic Medicine, 13, 851-860. https://doi.org/10.3892/etm.2017.4071
MLA
Zhu, M., Sun, X., Chen, X., Xiao, H., Duan, M., Xu, J."Impact of gabapentin on neuronal high voltage‑activated Ca2+ channel properties of injured‑side axotomized and adjacent uninjured dorsal root ganglions in a rat model of spinal nerve ligation". Experimental and Therapeutic Medicine 13.3 (2017): 851-860.
Chicago
Zhu, M., Sun, X., Chen, X., Xiao, H., Duan, M., Xu, J."Impact of gabapentin on neuronal high voltage‑activated Ca2+ channel properties of injured‑side axotomized and adjacent uninjured dorsal root ganglions in a rat model of spinal nerve ligation". Experimental and Therapeutic Medicine 13, no. 3 (2017): 851-860. https://doi.org/10.3892/etm.2017.4071
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team