Attempts to prevent equine post neurectomy neuroma formation through retrograde transport of two neurotoxins, doxorubicin and ricin.

This research paper details a study conducted to prevent the formation of painful neuromas in horses after neurectomy by delivering lethal doses of neurotoxins to the transected digital nerve fibres. It investigated two neurotoxins – doxorubicin and ricin, where doxorubicin was found ineffective in retrograde destruction of cell bodies but prevented Schwann cell proliferation and axon sprouting, whereas ricin was effective but too toxic to recommend for use.

Study Methodology and Findings

• Investigations were made through digital neurectomies on ponies, where neurotoxins were delivered to the digital nerve fibres. The aim was to use these toxic agents to halt regenerative changes that lead to neuroma formation.
• Doxorubicin was applied in varying ways to the digital nerve stumps. However, the results showcased only sporadic appearances of degenerating or necrotic neurones in the spinal ganglia. Hence, it was seen as largely ineffective in the retrograde destruction of neuron bodies.
• When doxorubicin was absorbed via pledgets on the stumps, it prevented Schwann cell proliferation and axon sprouting, thereby demonstrating a more sustained effect.
• Ricin, however, showed effectiveness where it led to the retrograde destruction of sensory neurons, with many affected neurons devoid of polysomes but packed with mitochondria, and others advancing to various stages in cytolysis. Despite this, its extreme toxicity precludes it as a recommended solution.

Implications and Future Directions

• Despite the toxicity of ricin, its effectiveness in destroying sensory neurons illustrates the potential for a solution if a less toxic agent could be found.
• The study points out that the use of retrograde transport in equine neurectomy would, in fact, hinge on the advancement and development of hybrid toxins, which would require high neural specificity and low systemic toxicity.
• There is potential for advancements in pain and lameness relief in equine cases through the further traversal of this research path.