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  • 1 Department of Anatomy, Histology and Embryology, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary
  • | 2 Department of Anatomy, Histology and Embryology, Faculty of Medicine, Medical and Health Science Center, University of Debrecen, Nagyerdei krt 98, H-4032, Debrecen, Hungary
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Abstract

It has been demonstrated that in the superficial spinal dorsal horn, Lamotrigine, which is known to block voltage-sensitive Na+ and Ntype Ca2+ channels, depresses neural activities evoked by sustained activation of nociceptive primary afferent fibres. In the present experiments, we study how Lamotrigine exerts its inhibitory effect on spinal nociceptive information-processing mechanisms. We show that Lamotrigine in an in vitro slice preparation effectively blocks synaptic transmission between primary afferents and secondary sensory neurons. Together with the robust increase in the failure rate and reduction in the amplitude of excitatory post-synaptic potentials (EPSPs) evoked by stimulation of nociceptive primary afferents, Lamotrigine causes a marked decrease in the number and amplitude of spontaneous EPSPs and a gradual shift of the resting membrane potential towards hyperpolarization. In addition, Lamotrigine treatment also changes the intrinsic firing pattern of superficial dorsal horn neurons. The results suggest that the effect of Lamotrigine on spinal nociceptive information-processing mechanisms is multiple: it depresses synaptic inputs from nociceptive primary afferents to secondary spinal sensory neurons and also weakens the intrinsic activities of nociceptive spinal neural circuits in the superficial spinal dorsal horn.

  • 1. J.C. Hunter K.R. Gogas L.R. Hedley L.O. Jacobson L. Kassotakis J. Thompson D.J. Fontana 1997 The effect of novel anti-epileptic drugs in rat experimental models of acute and chronic pain Eur J Pharmacol 324 153 160.

    • Search Google Scholar
    • Export Citation
  • 2. T.S. Jensen 2002 Anticonvulsants in neuropathic pain: rationale and clinical evidence Eur J Pain 6 Suppl. A 61 68.

  • 3. M.J. Leach C.M. Marden A.A. Miller 1986 Pharmacological studies on lamotrigine, a novel potential antiepileptic drug: II. Neurochemical studies on the mechanism of action Epilepsia 27 490 497.

    • Search Google Scholar
    • Export Citation
  • 4. H. Cheung D. Kamp E. Harris 1992 An in vitro investigation of the action of lamotrigine on neuronal voltage-activated sodium channels Epilepsy Res 13 107 112.

    • Search Google Scholar
    • Export Citation
  • 5. S.J. Wang C.C. Huang K.S. Hsu J.J. Tsai P.W. Gean 1996 Inhibition of Ntype calcium currents by lamotrigine in rat amygdalar neurones Neuroreport 7 3037 3040.

    • Search Google Scholar
    • Export Citation
  • 6. H.L. Teoh J. Fowler N.G. Bowery 1995 Effect of lamotrigine on the electrically-evoked release of endogenous amino acids from slices of dorsal horn of the rat spinal cord Neuropharmacology 34 1273 1278.

    • Search Google Scholar
    • Export Citation
  • 7. G. Blackburn-Munro S.M. Fleetwood-Walker 1997 The effects of Na+ channel blockers on somatosensory processing by rat dorsal horn neurones Neuroreport 8 1549 1554.

    • Search Google Scholar
    • Export Citation
  • 8. G. Blackburn-Munro S.M. Fleetwood-Walker 1999 The sodium channel auxiliary subunits beta1 and beta2 are differentially expressed in the spinal cord of neuropathic rats Neuroscience 90 153 164.

    • Search Google Scholar
    • Export Citation
  • 9. T.M. Laughlin K.V. Tram G.L. Wilcox A.K. Birnbaum 2002 Comparison of antiepileptic drugs tiagabine, lamotrigine, and gabapentin in mouse models of acute, prolonged, and chronic nociception J Pharmacol Exp Ther 302 1168 1175.

    • Search Google Scholar
    • Export Citation
  • 10. K.L. Petersen A. Maloney F. Hoke J.B. Dahl M.C. Rowbotham 2003 A randomized study of the effect of oral lamotrigine and hydromorphone on pain and hyperalgesia following heat/capsaicin sensitization J Pain 4 400 406.

    • Search Google Scholar
    • Export Citation
  • 11. Y. Kawasaki E. Kumamoto H. Furue M. Yoshimura 2003 Alpha 2 adrenoceptor-mediated presynaptic inhibition of primary afferent glutamatergic transmission in rat substantia gelatinosa neurons Anesthesiology 98 682 689.

    • Search Google Scholar
    • Export Citation
  • 12. W.A. Eckert K.K. McNaughton A.R. Light 2003 Morphology and axonal arborization of rat spinal inner lamina II neurons hyperpolarized by μ-opioid-selective agonists J Comp Neurol 458 240 256.

    • Search Google Scholar
    • Export Citation
  • 13. J.A. Lindia M.G. Kohler W.J. Martin C. Abbadie 2005 Relationship between sodium channel NaV1.3 expression and neuropathic pain behavior in rats Pain 117 145 153.

    • Search Google Scholar
    • Export Citation
  • 14. D.S. Ragsdale M. Avoli 1998 Sodium channels as molecular targets for antiepileptic drugs Brain Res Brain Res Rev 26 16 28.

  • 15. G. Blackburn-Munro N. Ibsen H.K. Erichsen 2002 A comparison of the anti-nociceptive effects of voltage-activated Na+ channel blockers in the formalin test Eur J Pharmacol 445 231 238.

    • Search Google Scholar
    • Export Citation
  • 16. E. Eisenberg A. Shifrin N. Krivoy 2005 Lamotrigine for neuropathic pain Expert Rev Neurother 5 729 735.

2019  
Scimago
H-index
11
Scimago
Journal Rank
0,220
Scimago
Quartile Score
Medicine (miscellaneous) Q3
Scopus
Cite Score
155/133=1,2
Scopus
Cite Score Rank
General Medicine 199/529 (Q2)
Scopus
SNIP
0,343
Scopus
Cites
206
Scopus
Documents
23

 

Interventional Medicine and Applied Science
Language English
Size  
Year of
Foundation
2009
Publication
Programme
changed title
Volumes
per Year
 
Issues
per Year
 
Founder Akadémiai Kiadó
Founder's
Address
H-1117 Budapest, Hungary 1516 Budapest, PO Box 245.
Publisher Akadémiai Kiadó
Publisher's
Address
H-1117 Budapest, Hungary 1516 Budapest, PO Box 245.
Responsible
Publisher
Chief Executive Officer, Akadémiai Kiadó
ISSN 2061-1617 (Print)
ISSN 2061-5094 (Online)

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