Mitigation of nociception via transganglionic degenerative atrophy: possible mechanism of vinpocetine-induced blockade of retrograde axoplasmic transport.
Vinpocetine, a derivative of vincamine, widely used in the clinical pharmacotherapy of cerebral circulatory diseases, inhibits retrograde axoplasmic transport of nerve growth factor (NGF) in the peripheral nerve, resulting in transganglionic degenerative atrophy (TDA) in the related ipsilateral superficial spinal dorsal horn, as shown in our previous publications. TDA induced by vinpocetine has been demonstrated to be followed by depletion of the marker enzyme fluoride-resistant acid phosphatase (FRAP) and its isoenzyme thiamine monophosphatase (TMP), and by the decrease in the pain-related neuropeptide substance P from laminae I-II-(III) from the segmentally related, ipsilateral substance of Rolando of the spinal cord. In the present paper, we report on the behavioral effects of perineurally administered vinpocetine. Nociception, induced by intraplantar injection of formalin, was mitigated by vinpocetine; increased expression of c-fos in the ipsilateral, segmentally related upper dorsal horn was also prevented. Since vinpocetine is not a microtubule inhibitor, and its chemical structure differs from that of vincristin and vinblastin (used formerly by us in the therapy of intractable, chronic neuropathic pain), its mode of action is enigmatic. We assume that the effect of vinpocetine in blocking retrograde axoplasmic transport of NGF might be related to its interaction with membrane trafficking proteins, such as signalling endosomes and the endocytosis-mediating "pincher" protein. Temporary, locally restricted decrease of nociception, induced by vinpocetine, might be useful in the clinical treatment of intractable, chronic neuropathic pain, since vinpocetine can successfully be applied by transcutaneous iontophoresis.
Csillik
Bertalan
B
Department of Anatomy, Albert Szent-Györgyi University Medical School, Szeged, Hungary. csillik@anatomy.szote.u-szeged.hu
Mihály
András
A
Krisztin-Péva
Beata
B
Farkas
Ibolya
I
Knyihár-Csillik
Elizabeth
E
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001370:Axonal Transport / Q000187:drug effects*; D004195:Disease Models, Animal; D008297:Male; D009410:Nerve Degeneration / Q000188:drug therapy* / Q000503:physiopathology; D010146:Pain / Q000503:physiopathology* / Q000517:prevention & control; D010147:Pain Measurement; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000187:drug effects / Q000503:physiopathology; D014748:Vinca Alkaloids / Q000494:pharmacology*
D000700:Analgesics; D016760:Proto-Oncogene Proteins c-fos; D014748:Vinca Alkaloids; C013983:vinpocetine