Skip to main content
SpringerLink
Log in

Voltage-gated sodium channels and visceral pain

  • Chapter
Sodium Channels, Pain, and Analgesia

Part of the book series: Progress in Inflammation Research ((PIR))

  • 765 Accesses

Summary

In conclusion the TTX-resistant sodium current, especially that produced by the NaV1.8 subunit, appears to be a strong candidate for a molecular substrate underlying sensitization of visceral afferent nociceptive neurons.

The visceral anti-nociceptive effects of agents that block sodium currents confirm an important role for these channels in visceral sensation. Intravenous lidocaine, a use-dependent sodium channel blocker, is effective in inhibiting both pseudoaffective reflex responses and spinal neuronal discharges to noxious distension of the colon [32]. Likewise, the sodium channel blockers mexiletine and carbamazepine dose-dependently inhibit the responses of nociceptive colonic afferent fibres to colorectal distension [33]. There have been very few clinical reports of the effects of sodium channel blockers on visceral pain [32, 34] although one report describes that systemic local anaesthetics were effective in relieving pain from the spleen [35]. However, indirect evidence comes from the observation that tricyclic antidepressant drugs like amitriptyline are regularly prescribed for functional visceral pain. Although these compounds likely exert their antidepressant effects by blocking the re-uptake of monoamines, many are also potent sodium channel blockers, and this feature may contribute to their effectiveness in some visceral pain patients.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Cervero F, Laird JM (1996) Mechanisms of touch-evoked pain (allodynia): a new model. Pain 68: 13–23

    Article  PubMed  CAS  Google Scholar 

  2. Hunt SP, Mantyh PW (2001) The molecular dynamics of pain control. Nat Rev Neurosci 2: 83–91

    Article  PubMed  CAS  Google Scholar 

  3. Cervero F, Laird JMA (1999) Visceral pain. Lancet 353: 2145–2148

    Article  PubMed  CAS  Google Scholar 

  4. Drossman DA, Camilleri M, Mayer EA, Whitehead WE (2002) AGA technical review on irritable bowel syndrome. Gastroenterology 123: 2108–2131

    Article  PubMed  Google Scholar 

  5. Lin C, Al Chaer ED (2003) Long-term sensitization of primary afferents in adult rats exposed to neonatal colon pain. Brain Res 971: 73–82

    Article  PubMed  CAS  Google Scholar 

  6. Cervero F (1994) Sensory innervation of the viscera: Peripheral basis of visceral pain. Physiol Rev 74: 95–138

    PubMed  CAS  Google Scholar 

  7. Mayer EA, Gebhart GF (1994) Basic and clinical aspects of visceral hyperalgesia. Gastroenterol 107: 271–293

    CAS  Google Scholar 

  8. Laird JMA, Roza C, Cervero F (1997) Effects of artificial calculosis on rat ureter motility: peripheral contribution to the pain of ureteric colic. Am J Physiol 272: R1409–1416

    PubMed  CAS  Google Scholar 

  9. Wood JN, Baker M (2001) Voltage-gated sodium channels. Curr Opin Pharmacol 1: 17–21

    PubMed  CAS  Google Scholar 

  10. Djouhri L, Fang X, Okuse K, Wood JN, Berry CM, Lawson SN (2003) The TTX-resistant sodium channel NaV1.8 (SNS/PN3): expression and correlation with membrane properties in rat nociceptive primary afferent neurons. J Physiol 550: 739–752

    Article  PubMed  CAS  Google Scholar 

  11. Fang X, Djouhri L, Black JA, Dib-Hajj SD, Waxman SG, Lawson SN (2002) The presence and role of the tetrodotoxin-resistant sodium channel NaV1.9 (NaN) in nociceptive primary afferent neurons. J Neurosci 22: 7425–7433

    PubMed  CAS  Google Scholar 

  12. Gold MS, Reichling DB, Shuster MJ, Levine JD (1996) Hyperalgesic agents increase a tetrodotoxin-resistant Na+ current in nociceptors. Proc Natl Acad Sci USA 93: 1108–1112

    Article  PubMed  CAS  Google Scholar 

  13. England S, Bevan S, Docherty RJ (1996) PGE2 modulates the tetrodotoxin-resistant sodium current in neonatal rat dorsal root ganglion neurones via the cyclic AMP-protein kinase A cascade. J Physiol 495: 429–440

    PubMed  CAS  Google Scholar 

  14. Cardenas CG, Del Mar LP, Cooper BY, Scroggs RS (1997) 5HT4 receptors couple positively to tetrodotoxin-insensitive sodium channels in a subpopulation of capsaicin-sensitive rat sensory neurons. J Neurosci 17: 7181–7189

    PubMed  CAS  Google Scholar 

  15. Bielefeldt K, Ozaki N, Gebhart GF (2002) Experimental ulcers alter voltage-sensitive sodium currents in rat gastric sensory neurons. Gastroenterol 122: 394–405

    CAS  Google Scholar 

  16. Bielefeldt K, Ozaki N, Gebhart GF (2002) Mild gastritis alters voltage-sensitive sodium currents in gastric sensory neurons in rats. Gastroenterol 122: 752–761

    CAS  Google Scholar 

  17. Moore BA, Stewart TM, Hill C, Vanner SJ (2002) TNBS ileitis evokes hyperexcitability and changes in ionic membrane properties of nociceptive DRG neurons. Am J Physiol Gastrointest Liver Physiol 282: G1045–G1051

    PubMed  CAS  Google Scholar 

  18. Su X, Wachtel RE, Gebhart GF (1999) Capsaicin sensitivity and voltage-gated sodium currents in colon sensory neurons from rat dorsal root ganglia. Am J Physiol 277: G1180–G1188

    PubMed  CAS  Google Scholar 

  19. Gold MS, Zhang L, Wrigley DL, Traub RJ (2002) Prostaglandin E(2) modulates TTXR I(Na) in rat colonic sensory neurons. J Neurophysiol 88: 1512–1522

    PubMed  CAS  Google Scholar 

  20. Beyak MJ, Ramji N, Krol KM, Kawaja MD, Vanner SJ (2004) Two TTX-resistant Na+ currents in mouse colonic dorsal root ganglia neurons and their role in colitis-induced hyperexcitability. Am J Physiol Gastrointest Liver Physiol 287: G845–855

    Article  PubMed  CAS  Google Scholar 

  21. Yoshimura N, De Groat WC (1999) Increased excitability of afferent neurons innervating rat urinary bladder after chronic bladder inflammation. J Neurosci 19: 4644–4653

    PubMed  CAS  Google Scholar 

  22. Yoshimura N, White G, Weight F, De Groat WC (1996) Different types of Na+ and K+ currents in rat dorsal root ganglion neurones innervating the urinary bladder. J Physiol 494: 1–16

    PubMed  CAS  Google Scholar 

  23. Akopian AN, Sivilotti L, Wood JN (1996) A tetrodotoxin-resistant voltage-gated sodium channel expressed by sensory neurons. Nature 379: 257–262

    Article  PubMed  CAS  Google Scholar 

  24. Cummins TR, Dib-Hajj SD, Black JA, Akopian AN, Wood JN, Waxman SG (1999) A novel persistent tetrodotoxin-resistant sodium current in SNS-null and wild-type small primary sensory neurons. J Neurosci 19: RC43

    PubMed  CAS  Google Scholar 

  25. Black JA, Cummins TR, Yoshimura N, de Groat WC, Waxman SG (2003) Tetrodotoxin-resistant sodium channels NaV1.8/SNS and NaV1.9/NaN in afferent neurons innervating urinary bladder in control and spinal cord injured rats. Brain Res 963: 132–138

    Article  PubMed  CAS  Google Scholar 

  26. Tanaka M, Cummins TR, Ishikawa K, Dib-Hajj SD, Black JA, Waxman SG (1998) SNS Na+ channel expression increases in dorsal root ganglion neurons in the carrageenan inflammatory pain model. Neuroreport 9: 967–972

    PubMed  CAS  Google Scholar 

  27. Akopian AN, Souslova V, England S, Okuse K, Ogata N, Ure J, Smith A, Kerr BJ, McMahon SB, Boyce S et al (1999) The tetrodotoxin-resistant sodium channel SNS has a specialized function in pain pathways. Nat Neurosci 2: 541–548

    PubMed  CAS  Google Scholar 

  28. Laird JMA, Souslova V, Wood JN, Cervero F (2002) Deficits in visceral pain and referred hyperalgesia in NaV1.8 (SNS/PN3)-null mice. J Neurosci 22: 8352–8356

    PubMed  CAS  Google Scholar 

  29. Laird JMA, Martinez-Caro L, Garcia-Nicas E, Cervero F (2001) A new model of visceral pain and referred hyperalgesia in the mouse. Pain 92: 335–342

    Article  PubMed  CAS  Google Scholar 

  30. Olivar T, Laird JMA (1999) Cyclophosphamide cystitis in mice: behavioural characterization and correlation with bladder inflammation. Eur J Pain 3: 141–149

    Article  PubMed  Google Scholar 

  31. Yoshimura N, Seki S, Novakovic SD, Tzoumaka E, Erickson VL, Erickson KA, Chancellor MB, De Groat WC (2001) The involvement of the tetrodotoxin-resistant sodium channel NaV1.8 (PN3/SNS) in a rat model of visceral pain. J Neurosci 21: 8690–8696

    PubMed  CAS  Google Scholar 

  32. Ness TJ (2000) Intravenous lidocaine inhibits visceral nociceptive reflexes and spinal neurons in the rat. Anesthesiol 92: 1685–1691

    CAS  Google Scholar 

  33. Su X, Joshi SK, Kardos S, Gebhart GF (2002) Sodium channel blocking actions of the kappa-opioid receptor agonist U-50,488 contribute to its visceral antinociceptive effects. J Neurophysiol 87: 1271–1279

    PubMed  CAS  Google Scholar 

  34. Glazer S, Portenoy RK (1991) Systemic local anesthetics in pain control. J Pain Sympt Manage 6: 30–39

    Article  CAS  Google Scholar 

  35. Parris WC, Gerlock AJ Jr, MacDonell RC Jr (1981) Intra-arterial chloroprocaine for the control of pain associated with partial splenic embolization. Anesth Analg 60: 112–115

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Bioscience Department, AstraZeneca R&D Montréal, 7171 Frédérick-Banting, Ville Saint-Laurent, Quebec, H4S 1Z9, Canada

    Jennifer M.A Laird

  2. Anaesthesia Research Unit and Centre for Research on Pain, McGill University, Montréal, Quebec, Canada

    Fernando Cervero

  3. Pharmacology and Experimental Therapeutics, McGill University, Montréal, Quebec, Canada

    Jennifer M.A Laird

Authors
  1. Jennifer M.A Laird
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fernando Cervero
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jennifer M.A Laird
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. PLIVA Research Institute Ltd., Prilaz baruna Filipovića 29, HR-10000, Zagreb, Croatia

    Michael J. Parnham PhD (Senior Scientific Advisor) (Senior Scientific Advisor)

  2. Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3QT, UK

    Kevin Coward

  3. Molecular Nociception Group Department of Biology Medawar Building, University College London, Gower Street, London, WC1E 6BT, UK

    Mark D. Baker

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Birkhäuser Verlag Basel/Switzerland

About this chapter

Cite this chapter

Laird, J.M., Cervero, F., Laird, J.M. (2005). Voltage-gated sodium channels and visceral pain. In: Parnham, M.J., Coward, K., Baker, M.D. (eds) Sodium Channels, Pain, and Analgesia. Progress in Inflammation Research. Birkhäuser Basel. https://doi.org/10.1007/3-7643-7411-X_3

Download citation

  • DOI: https://doi.org/10.1007/3-7643-7411-X_3

  • Publisher Name: Birkhäuser Basel

  • Print ISBN: 978-3-7643-7062-6

  • Online ISBN: 978-3-7643-7411-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation