engleski

Botulinum toxin's axonal transport: implications for pain and movement disorder treatment?

Introduction: Use of botulinum toxin has been approved in movement disorders like blepharospasm, focal dystonias and, recently, chronic migraine. Widely assumed peripheral mechanism of action has been questioined by recent studies which demonstrated axonal transport in facial and sciatic nerve. Moreover, axonal transport has been shown to be necessary for its antinociceptive effect. Materials&methods Botulinum toxin's central enzymatic activity has been assessed using immunohistochemical detection of its cleaved substrate synaptosomal-associated protein 25 (SNAP-25) in rat lumbal spinal cord and brainstem following subcutaneous injection in rat hind-paw and whisker pad, intramuscular injection into the gastrocnemius muscle and intraneural injections in sciatic and facial nerve. To confirm microtubule-dependent axonal transport, sciatic nerve was pretreated with saline or colchicine prior to intraneural injection toxin into the sciatic nerve. Results Cleaved SNAP-25 following subcutaneous, intramuscular and intraneural toxin injection in rat hind limbs has been observed in corresponding segments of ipsilateral dorsal and ventral horn. Retrograde ascent in facial motoneurons has been observed following injection into the whisker pad and exposed facial nerve. Following axonal transport in trigeminal nerve cleaved SNAP-25 has been observed in spinal trigeminal nucleus caudalis and oralis. Colchicine prevented the occurence of central cleaved SNAP-25 following intraneural injection into sciatic nerve. Conclusion Botulinum toxin's axonal transport in different sensory and motor neurons is likely to be a common occurence after peripheral application, over long distances. Since axonal transport in sensory neurons is shown to be involved in botulinum toxin's antinociceptive activity, possible functional role of axonal transport in motor neurons for movement disorder treatment remains to be examined. Acknowledgements: Antibody to cleaved SNAP-25 is a kind gift from Ornella Rossetto, University of Padua, Italy. Sources of funding: Croatian Ministry of Science, Education and Sport and Deutscher Academischer Austauch Dienst.

botulinum toxin type A; pain; movement disorders; axonal transport

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