Attempts to prevent equine post neurectomy neuroma formation through retrograde transport of two neurotoxins, doxorubicin and ricin.
Digital neurectomies, performed to relieve pain and lameness, are often complicated postoperatively by formation of painful neuromas. In this study attempts were made to deliver lethal doses of neurotoxin to the cell bodies of the transected digital nerve fibres via long-distance retrograde axon transport and, thereby, prevent the regenerative changes that lead to neuroma formation. After applying doxorubicin in various ways to the digital nerve stumps of ponies, degenerating or necrotic neurones appeared only sporadically in the spinal ganglia. Although doxorubicin was largely ineffective in retrograde destruction of cell bodies, when absorbed in pledgets on the stumps it exerted a sustained action which prevented Schwann cell proliferation and axon sprouting. Ricin, in contrast to doxorubicin, was effective in retrograde destruction of sensory neurons. Many affected neurons were devoid of polysomes but packed with mitochondria; others had advanced to various stages in cytolysis. Despite its effectiveness, ricin cannot be recommended because of its extreme toxicity. The clinical use of retrograde transport in equine neurectomy will probably depend on future development of hybrid toxins with high neural specificity and low systemic toxicity.
Cummings
J F
JF
Department of Anatomy, New York State College of Veterinary Medicine, Cornell University, Ithaca 14853.
Fubini
S L
SL
Todhunter
R J
RJ
D000818:Animals; D001370:Axonal Transport; D001369:Axons / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D004317:Doxorubicin / Q000627:therapeutic use*; D005260:Female; D006734:Horse Diseases / Q000517:prevention & control*; D006736:Horses; D008297:Male; D008854:Microscopy, Electron; D009416:Nerve Regeneration / Q000187:drug effects; D009463:Neuroma / Q000517:prevention & control / Q000662:veterinary*; D009475:Neurons, Afferent / Q000187:drug effects; D010525:Peripheral Nerves / Q000601:surgery*; D011183:Postoperative Complications / Q000517:prevention & control / Q000662:veterinary*; D012276:Ricin / Q000009:adverse effects / Q000627:therapeutic use*
D004317:Doxorubicin; D012276:Ricin