Skip to main content
Log in

Effects of carbamazepine and amitriptyline on tetrodotoxin-resistant Na+ channels in immature rat trigeminal ganglion neurons

  • Articles
  • Drug Efficacy and Safety
  • Published:
Archives of Pharmacal Research Aims and scope Submit manuscript

Abstract

Although anticonvulsant drugs that block voltage-dependent Na+ channels have been widely used for neuropathic pain, including peripheral nerve injury-induced pain, much less is known about the actions of these drugs on immature trigeminal ganglion (TG) neurons. Here we report the effects of carbamazepine (CBZ) and amitriptyline (ATL) on tetrodotoxin-resistant (TTX-R) Na+ channels expressed on immature rat TG neurons. TTX-R Na+ currents (INa) were recorded in the presence of 300 nM TTX by use of a conventional whole-cell patch clamp method. Both CBZ and ATL inhibited TTX-R INa in a concentration-dependent manner, but ATL was more potent. While CBZ and ATL did not affect the overall voltage-activation relationship of TTX-R Na+ channels, both drugs shifted the voltage-activation relationship to the left, indicating that they inhibited TTX-R Na+ channels more efficiently at depolarized membrane potentials. ATL showed a profound use-dependent blockade of TTX-R INa, but CBZ had little effect. The present results suggest that both CBZ and ATL, common drugs used for treating neuropathic pain, efficiently inhibit TTX-R Na+ channels expressed on immature TG neurons, and that these drugs might be useful for the treatment of trigeminal nerve injury-induced neuropathic pain, as well as the inhibition of ongoing central sensitization, even during immature periods.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Akaike, N. and Harata, N., Nystatin perforated patch recording and its application to analysis of intracellular mechanism. Jpn. J. Physiol., 44, 433–473 (1994).

    Article  PubMed  CAS  Google Scholar 

  • Akopian, A. N., Souslova, V., England, S., Okuse, K., Ogata, N., Ure, J., Smith, A., Kerr, B. J., McMahon, S. B., Boyce, S., Hill, R., Stanfa, L. C., Dickenson, A. H., and Wood, J. N., The tetrodotoxin-resistant sodium channel SNS has a specialized function in pain pathways. Nat. Neurosci., 2, 541–548 (1999).

    Article  PubMed  CAS  Google Scholar 

  • Amir, R., Michaelis, M., and Devor, M., Membrane potential oscillations in dorsal root ganglion neurons: role in normal electrogenesis and neuropathic pain. J. Neurosci., 19, 8589–8596 (1999).

    PubMed  CAS  Google Scholar 

  • Back, S. K., Kim, M. A., Kim, H. J., Yoon, Y., Hong, S. K., and Na, H. S., Neuropathic pain behaviors induced by peripheral nerve injury at neonatal rats. Soc. Neurosci. Abs., 31, No. 512.11. (2005).

  • Backonja, M. M., Use of anticonvulsants for treatment of neuropathic pain. Neurology, 59, S14–S17 (2002).

    PubMed  Google Scholar 

  • Baker, K. A., Taylor, J. W., and Lilly, G. E., Treatment of trigeminal neuralgia: use of baclofen in combination with carbamazepine. Clin. Pharm., 4, 93–96 (1985).

    PubMed  CAS  Google Scholar 

  • Bräu, M. E., Dreimann, M., Olschewski, A., Vogel, W., and Hempelmann, G., Effect of drugs used for neuropathic pain management on tetrodotoxin-resistant Na+ currents in rat sensory neurons. Anesthesiology, 94, 137–144 (2001).

    Article  PubMed  Google Scholar 

  • Brock, J. A., McLachlan, E. M., and Belmonte, C., Tetrodotoxin-resistant impulses in single nociceptor nerve terminals in guinea-pig cornea. J. Physiol. (Lond.), 512, 211–217 (1998).

    Article  CAS  Google Scholar 

  • Campbell, J. N. and Meyer, R. A., Mechanisms of neuropathic pain, Neuron, 52, 77–92 (2005).

    Article  CAS  Google Scholar 

  • Davies, S. L., Loescher, A. R., Clayton, N. M., Bountra, C., Robinson, P. P., and Boissonade, F. M., Changes in sodium channel expression following trigeminal nerve injury. Exp. Neurol., 202, 207–216 (2006).

    Article  PubMed  CAS  Google Scholar 

  • Elliott, A. A. and Elliott, J. R., Characterization of TTX-sensitive and TTX-resistant sodium currents in small cells from adult rat dorsal root ganglia. J. Physiol. (Lond.), 463, 39–56 (1993).

    CAS  Google Scholar 

  • Kajander, K. C. and Bennett, G. J., Onset of a painful peripheral neuropathy in rat: a partial and differential deafferentation and spontaneous discharge in A beta and A delta primary afferent neurons. J. Neurophysiol., 68, 734–744 (1992).

    PubMed  CAS  Google Scholar 

  • LaMotte, R. H., Shain, C. N., Simone, D. A., and Tsai, E. F. P., Neurogenic hyperalgesia: Psychophysical studies of underlying mechanisms. J. Neurophysiol., 66, 190–211 (1991).

    PubMed  CAS  Google Scholar 

  • Lee, D. H. and Chung, J. M., Neuropathic pain in neonatal rats. Neurosci. Lett., 209, 140–142 (1996).

    Article  PubMed  CAS  Google Scholar 

  • Leffler, A., Reiprich, A., Mohapatra, D. P., and Nau, C., Usedependent block by lidocaine but not amitriptyline is more pronounced in tetrodotoxin (TTX)-resistant Nav1.8 than in TTX-sensitive Na+ channels. J. Pharmacol. Exp. Ther., 320, 354–364 (2007).

    Article  PubMed  CAS  Google Scholar 

  • Liu, B. and Eisenach, J. C., Hyperexcitability of axotomized and neighboring unaxotomized sensory neurons is reduced days after perineural clonidine at the site of injury. J. Neurophysiol., 94, 3159–3167 (2005).

    Article  PubMed  CAS  Google Scholar 

  • Liu, C. N., Wall, P. D., Ben-Dor, E., Michaelis, M., Amir, R., and Devor, M., Tactile allodynia in the absence of C-fiber activation: altered firing properties of DRG neurons following spinal nerve injury. Pain, 85, 503–521 (2000).

    Article  PubMed  CAS  Google Scholar 

  • Matzner, O. and Devor, M., Na+ conductance and the threshold for repetitive neuronal firing. Brain Res., 597, 92–98 (1992).

    Article  PubMed  CAS  Google Scholar 

  • Matzner, O. and Devor, M., Hyperexcitability at sites of nerve injury depends on voltage-sensitive Na+ channels. J. Neurophysiol., 72, 349–359 (1994).

    PubMed  CAS  Google Scholar 

  • Novakovic, S. D., Tzoumaka, E., McGivern, J. G., Haraguchi, M., Sangameswaran, L., Gogas, K. R., Eglen, R. M., and Hunter, J. C., Distribution of the tetrodotoxin-resistant sodium channel PN3 in rat sensory neurons in normal and neuro-pathic conditions. J. Neurosci., 18, 2174–2187 (1998).

    PubMed  CAS  Google Scholar 

  • Rush, A. M. and Elliott, J. R., Phenytoin and carbamazepine: differential inhibition of sodium currents in small cells from adult rat dorsal root ganglia. Neurosci. Lett., 226, 95–98 (1997).

    Article  PubMed  CAS  Google Scholar 

  • Schild, J. H. and Kunze, D. L., Experimental and modeling study of Na+ current heterogeneity in rat nodose neurons and its impact on neuronal discharge. J. Neurophysiol., 78, 3198–3209 (1997).

    PubMed  CAS  Google Scholar 

  • Sidebottom, A. and Maxwell, S., The medical and surgical management of trigeminal neuralgia, J. Clin. Pharm. Ther., 20, 31–35 (1995).

    Article  PubMed  CAS  Google Scholar 

  • Tanelian, D. L. and Brose, W. G., Neuropathic pain can be relieved by drugs that are use-dependent sodium channel blockers: lidocaine, carbamazepine, and mexiletine. Anesthesiology, 74, 949–951 (1991).

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Il-Sung Jang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hur, YK., Choi, IS., Cho, JH. et al. Effects of carbamazepine and amitriptyline on tetrodotoxin-resistant Na+ channels in immature rat trigeminal ganglion neurons. Arch. Pharm. Res. 31, 178–182 (2008). https://doi.org/10.1007/s12272-001-1138-x

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12272-001-1138-x

Key words

Navigation