Antinociceptive effect of vinpocetine - A comprehensive survey

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Abstract

Blockade of retrograde transport of nerve growth factor (NGF) in a peripheral sensory nerve is known to induce transganglionic degenerative atrophy (TDA) of central sensory terminals in the upper dorsal horn of the related, ipsilateral segments(s) of the spinal cord. The ensuing temporary blockade of transmission of nociceptive impulses has been utilized in the therapy of intractable pain, using transcutaneous iontophoresis of the microtubule inhibitors vincristin and vinblastin, drugs which inhibit retrograde transport of NGF. Since microtubule inhibition might inhibit (at least theoretically) mitotic processes in general, we sought to find a drug which inhibits retrograde transport of NGF without microtubule inhibition. Vinpocetine, a derivate of vincamine, which does not interfere with microtubular function, was found to inhibit retrograde axoplasmic transport of NGF in peripheral sensory nerves, similarly to vincristin and vinblastin. Blockade of NGF transport is followed by transganglionic degenerative atrophy in the segmentally related, ipsilateral superficial spinal dorsal horn, characterized by depletion of the marker enzymes of nociception, fluoride resistant acid phosphatase (FRAP) and thiamine monophosphatase (TMP) from the Rolando substance and by decrease of the pain-related neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) from lamina I-II-III. Based upon these findings, it has been suggested that vinpocetine may result in a locally restricted decrease of nociception. Herewith, the structural and behavioral effects of perineurally administered vinpocetine are discussed. Nociception, induced by intraplantar injection of formalin, was mitigated by perineural application of vinpocetine; also formalin-induced expression of c-fos in the ipsilateral, segmentally related superficial dorsal horn, was prevented by this treatment. Since vinpocetine is not a microtubule inhibitor, its mode of action is enigmatic. It is assumed that the effect of vinpocetine might be related to interaction with membrane-trafficking proteins, such as signalling endosomes and the endocytosis-mediating "pincher" protein, involved in retrograde axoplasmic transport of NGF, or to interaction with glial elements, recently reported to be involved in the modulation of pain in the spinal cord. Based on animal experiments it is assumed that the temporary, locally restricted decrease of nociception, induced by vinpocetine applied via transcutaneous iontophoresis, might open up new avenues in the clinical treatment of intractable pain.

Original languageEnglish
Pages (from-to)185-192
Number of pages8
JournalIdeggyógyászati szemle
Volume63
Issue number5-6
Publication statusPublished - May 30 2010

Fingerprint

vinpocetine
Nerve Growth Factor
Nociception
Microtubules
Iontophoresis
Intractable Pain
Axonal Transport
Peripheral Nerves
Formaldehyde
Atrophy
Spinal Cord
Vincamine
Pain
Calcitonin Gene-Related Peptide
Endosomes
Substance P
Acid Phosphatase
Endocytosis
Surveys and Questionnaires
Neuropeptides

Keywords

  • Axoplasmic transport
  • Glia
  • Nerve growth factor
  • Nociception
  • Pain
  • Pincher protein
  • Vinca alkaloids

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Antinociceptive effect of vinpocetine - A comprehensive survey. / Csillik, B.; Mihály, A.; Knyihár-Csillik, E.

In: Ideggyógyászati szemle, Vol. 63, No. 5-6, 30.05.2010, p. 185-192.

Research output: Contribution to journalArticle

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