Elsevier

Neuroscience

Volume 164, Issue 2, 1 December 2009, Pages 573-577
Neuroscience

Clinical Neuroscience
Research Paper
Abnormal expression of voltage-gated sodium channels Nav1.7, Nav1.3 and Nav1.8 in trigeminal neuralgia

https://doi.org/10.1016/j.neuroscience.2009.08.037Get rights and content

Abstract

Voltage-gated sodium channels have been implicated in acute and chronic neuropathic pain. Among subtypes, Nav1.7 single mutations can cause congenital indifference to pain or chronic neuropathic pain syndromes, including paroxysmal ones. This channel is co-expressed with Nav1.8, which sustains the initial action potential; Nav1.3 is an embrionary channel which is expressed in neurons after injury, as in neuropathic conditions. Few studies are focused on the expression of these molecules in human tissues having chronic pain. Trigeminal neuralgia (TN) is an idiopathic paroxysmal pain treated with sodium channel blockers. The aim of this study was to investigate the expression of Nav1.3, Nav1.7 and Nav1.8 by RT-PCR in patients with TN, compared to controls. The gingival tissue was removed from the correspondent trigeminal area affected. We found that Nav1.7 was downregulated in TN (P=0.017) and Nav1.3 was upregulated in these patients (P=0.043). We propose a physiopathological mechanism for these findings. Besides vascular compression of TN, this disease might be also a channelopathy.

Section snippets

Subject's selection

This was a randomized case×control study. Ten patients with TN according to the IASP (International Association for the Study of Pain) criteria (Merskey and Bogduk, 1994) were randomized for this study. In the moment of diagnosis, all had made computed tomography with contrast and/or magnetic resonance imaging and we did not find any abnormalities in the entry zone of the trigeminal root or other findings in any patient. All patients had been followed at the Orofacial Pain Clinic of a General

Patients' characteristics

The characteristics of the groups can be observed in Table 2 (n=23). TN ages were lower than in previous studies possibly because in general these patients need neurosurgery after some years with pain and we wanted to include only patients with recent pain onset and no surgery's history. In general, TN studies do not exclude previous operation. All TN patients had paroxysmal shock-like pain and all of them reported the maximum pain intensity (visual analogic scale—VAS=10). In the neurological

Discussion

The interest in the last decade in studying the role of voltage-gated sodium channels in chronic pain have grown, mainly because of the recent findings about single mutations that can cause pain disorders or indifference to pain (Ahmad et al 2007, Cox et al 2006, Goldberg et al 2007). Subtype Nav1.7 is particularly important, but also Nav1.8 and Nav1.3 are expressed in many chronic pain conditions (Cummins et al 2007, Dib-Hajj et al 2007, Rogers et al 2006, Rush et al 2006). In our study, we

Conclusion

There was a reduction in the expression of Nav1.7 and an increase in the expression of Nav1.3 when compared to controls; TN can be, at least in part, a channelopathy.

References (32)

  • J.A. Black et al.

    Multiple sodium channel isoforms and mitogen-activated protein kinases are present in painful human neuromas

    Ann Neurol

    (2008)
  • W.A. Catterall

    Molecular properties of brain sodium channels: an important target for anticonvulsant drugs

    Adv Neurol

    (1999)
  • J.S. Choi et al.

    Inherited erythermalgia: limb pain from an S4 charge-neutral Na channelopathy

    Neurology

    (2006)
  • J.J. Cox et al.

    An SCN9A channelopathy causes congenital inability to experience pain

    Nature

    (2006)
  • H. Dommisch et al.

    Differential gene expression of human β-defensins (hBD-1, -2, -3) in inflammatory gingival diseases

    Oral Microbiol Immunol

    (2005)
  • M. Estacion et al.

    NaV17 gain-of-function mutations as a continuum: A1632E displays physiological changes associated with erythromelalgia and paroxysmal extreme pain disorder mutations and produces symptoms of both disorders

    J Neurosci

    (2008)
  • Cited by (103)

    View all citing articles on Scopus
    View full text