Botulinum toxin’s axonal transport from periphery to the spinal cord

Axonal transport of enzymatically active botulinum toxin A (BTX-A) from periphery to the CNS has been described in facial and trigeminal nerve, leading to cleavage of synaptosomal-associated protein 25 (SNAP-25) in central nuclei. Aim of present study was to examine the existence of axonal transport of peripherally applied BTX-A to spinal cord via sciatic nerve.We employed BTX-A-cleaved SNAP-25 immunohistochemistry of lumbar spinal cord after intramuscular and subcutaneous hind limb injections, and intraneural BTX-A sciatic nerve injections. Truncated SNAP-25 in ipsilateral spinal cord ventral horns and dorsal horns appeared after single peripheral BTX-A administrations, even at low intramuscular dose applied (5 U/kg). Cleaved SNAP-25 appearance in the spinal cord after BTX-A injection into the sciatic nerve was prevented by proximal intrasciatic injection of colchicine (5 mM, 2 μl). Cleaved SNAP-25 in ventral horn, using choline-acetyltransferase (ChAT) double labeling, was localized within cholinergic neurons.These results extend the recent findings on BTX-A retrograde axonal transport in facial and trigeminal nerve. Appearance of truncated SNAP-25 in spinal cord following low-dose peripheral BTX-A suggest that the axonal transport of BTX-A occurs commonly following peripheral application.

Graphical abstractOccurrence of cleaved SNAP-25 in ipsilateral lumbal ventral horn following botulinum toxin A (30 U/kg) subcutaneous injection into the rat hind paw.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Peripheral BTX-A cleaves SNAP-25 in dorsal and ventral horn of the spinal cord. ► Axonal transport of BTX-A occurs at low intramuscular dose. ► BTX-A retrograde transport occurs via peripheral nerves and is microtubule-dependent. ► Truncated SNAP-25 is localized within cholinergic neurons of the ventral horn.