Alterations in the structure, function, and chemistry of C fibers following local application of vinblastine to the sciatic nerve of the rat.
Vinblastine, a transport blocker, was applied locally to the sciatic nerve in rats. It was found to be a powerful neurotoxin with a dose-dependent action, destroying all afferents at doses of 5 X 10(-4)M, primarily C fibers at intermediate doses of 2.5 X 10(-4)M, and only at a critically low dose of 10(-4)M was a degeneration-free axon transport blockade, lasting for 4 to 5 days, produced. Such transport block failed to alter thermal responsiveness of the rats as measured behaviorally, by the flexor reflex, or by dorsal horn cell responses. It did, however, significantly reduce both the chemical sensitivity of the C afferents and their ability to produce neurogenic edema. This began 24 hr after treatment and lasted 4 to 5 days. Therefore, it is likely that these functions are dependent on the continuous transport of some compound to the axon terminals from the cell body. This low concentration of local vinblastine treatment also resulted in depletion of fluoride-resistant acid phosphatase from C fiber terminals in the dorsal horn of the spinal cord. Transmission from C fibers to second-order neurons in the spinal cord, however, was totally unaffected. Substance P levels in the spinal terminals was largely unaffected, although in 1 of 5 cases there was depletion. It appears, therefore, that some, but not all, retrograde changes in sensory neurons following peripheral nerve damage can be mimicked by blockade of axon transport. The effects following vinblastine treatment are compared to other peripheral nerve manipulations, such as cut, crush, and application of local capsaicin.
D000344:Afferent Pathways / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001370:Axonal Transport; D004553:Electric Conductivity / Q000187:drug effects; D005260:Female; D008297:Male; D008854:Microscopy, Electron; D009132:Muscles / Q000294:innervation; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D012584:Sciatic Nerve / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D012867:Skin / Q000294:innervation; D014747:Vinblastine / Q000494:pharmacology*
D014747:Vinblastine