engleski

Update on botulinum toxin and pain

Only definitively known molecular target of botulinum toxin type A is SNAP-25, a protein involved in neurotransmitter vesicle release. Association of this effect with acetylcholine release in the neuromuscular junction is a textbook knowledge. However, in series of experiments we and other authors demonstrated that botulinum toxin reduces also inhibits pain perception, presumably inhibiting release of other neurotransmitters than acetylcholine. Up to now it is shown that botulinum toxin (BTX) does not reduce acute superficial nociceptive pain like thermal" (hot plate), "mechanical" pain (paw pressure test), but it reduces longer acting chemical pain like carageenan, capsaicin and second phase of formalin-induced pain. Up to now its action on visceral pain is shown only in capsaicin-induced prostate pain. The effect on deep somatic pain was investigated in formalin-induced knee joint pain. BTX reduces also a neuropathic pain induced by nerve ligature, diabetes or cytostatic paclitaxel. In comparison to several classical analgesics, BTX reduced only second phase of pain induced by subcutaneous injection of formalin. Potentially the greatest benefit of BTX might be its long lasting effect. Opposite of a different report we found that BTX is effective even after multiple applications. In several pain models we demonstrated that antinociceptive effect of peripherally applied BTX is axonal transport dependent. After BTX peripheral injection recently we found immunohistochemical evidence of enzymatic activity of BTX in central sensory areas. Our additional experiments completely excluded the possibility that peripheral sensory nerve endings contribute to antinociceptive effect of BTX. Discovery that BTX action on pain is exclusively a central effect rises many new questions: is it associated only with some neurotransmitters, or only with some types of nerves, or only with some types of ion channels? Is BTX associated with central synaptic remodeling like in neuromuscular junction? In conclusion we must admit that after these new discoveries we understand less than we previously (wrongly) believed. Supported by Croatian Ministry of Science, Education and Sport and Deutscher Academischer Austauch Dienst.

botulinum toxin type A; antinociceptive activity; sensory neurons; axonal transport

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