formyl-leurosine and Nerve-Degeneration

Latency to the hind-paw lick in the hot-plate test (54 degrees C) is significantly increased (P less than 0.001) in the course of transganglionic degenerative atrophy of central terminals of primary sensory neurons. This was induced by a 30 min perineural application of 10(-8) mol Formyl-Leurosin, which results in the blockade of retrograde axoplasmic transport without Wallerian degeneration of the peripheral nerve. Values of latency return to normal in the course of synaptoneogenetic restoration of neuronal connectivity in the upper dorsal horn. The results are compatible with the working hypothesis that the beneficial effect of chronic pain therapy with Vinca alkaloid iontophoresis might be due to the fact that transganglionic degenerative atrophy is followed by the establishment of a sound, normal wiring in the upper dorsal horn in the course of restorative synaptoneogenesis.

Topics: Acid Phosphatase; Animals; Atrophy; Axonal Transport; Female; Ganglia, Spinal; Nerve Degeneration; Neurons, Afferent; Pain; Rats; Reaction Time; Sciatic Nerve; Spinal Cord; Substantia Gelatinosa; Vinblastine; Vinca Alkaloids; Vincristine

If applied locally around a peripheral sensory nerve, Formyl-Leurosin, a semi-synthetic diindol alkaloid of Vinca rosea--that, just like other mitotic spindle inhibitors, induces blockade of axoplasmic transport via inhibiting microtubular function--causes transganglionic degenerative atrophy of central terminals of primary nociceptive neurons in the substantia gelatinosa Rolandi of the spinal cord. In contrast, if applied to dorsal roots, Formyl-Leurosin fails to induce such alterations. Based upon these observations it is postulated that blockade of retrograde axoplasmic transport, rather than that of the orthograde one, is the decisive factor in the pathomechanism of transganglionic degenerative atrophy.

Topics: Animals; Atrophy; Axonal Transport; Female; Ganglia, Spinal; Male; Nerve Degeneration; Nociceptors; Rats; Retrograde Degeneration; Vinca Alkaloids

Transcutaneous iontophoresis of microtubule inhibitors (Vinblastin, Vincristin, Formyl-Leurosin) in rats induces depletion of fluoride-resistant acid phosphatase (FRAP) and transganglionic degenerative atrophy (trggl. deg. atr.) of the central terminals of primary nociceptive neurons, probably via blockade of axoplasmic transport in the peripheral sensory nerves. Radiochemical experiments prove that about 0.2% of the microtubule inhibitors applied iontophoretically at the skin reach the level of nociceptive axon terminals. 40 out of 48 patients suffering from chronic intractable pain of diverse etiology (postherpetic, paresthetic, ischaemic and trigeminal neuralgia, alcoholic and diabetic polyneuropathy, meralgia, brachialgia, discopathia, arthropathia and terminal pain) were successfully treated with Vinblastin or Vincristin iontophoresis. Iontophoretically applied microtubule inhibitors do not affect the blood cell count, have no side-effects and do not impair the skin at the site of application.

Topics: Acid Phosphatase; Animals; Atrophy; Axonal Transport; Humans; Iontophoresis; Microtubules; Muridae; Nerve Degeneration; Nociceptors; Substantia Gelatinosa; Vinblastine; Vinca Alkaloids; Vincristine; Wallerian Degeneration