engleski

Immunohistochemical localization of botulinum toxin type A action on central nociceptive transmission

Studies from our laboratory demonstrated that the antinociceptive activity of botulinum toxin A (BTX-A), a recently approved antimigraine drug, is dependent on its axonal transport within sensory neurons to central nociceptive nuclei. Aim of this study was to immunohistochemically characterize the cellular and regional sites of BTX-A action on central pain transmission. BTX-A proteolytic activity in brain following toxin’s peripheral facial application in rats was detected using cleaved synaptosomal-associated protein 25 (SNAP-25) immunohistochemistry. Toxin’s localization in dorsal horn central afferent terminals was assessed using trigeminal ganglion ablation with formalin. SNAP-25 cleavage was examined in caudal medulla, thalamus, hypothalamus and sensory cortex. Localization of BTX-A-cleaved SNAP-25 in trigeminal nucleus caudalis (TNC) was studied in relation to immunohistochemical markers of neurons, dendrites, astrocytes, and presynaptic marker synaptophysin. Effect of BTX-A on c-Fos expression in different sensory regions was assessed in formalin-induced facial pain. Cleaved SNAP-25 dissapearance from TNC following the ablation of trigeminal nerve demonstrated its presence in central afferent terminals. Cleaved SNAP-25 colocalized with synaptophysin, but did not colocalize with markers of dendrites, astrocytes and neuronal nuclei. Proteolytic BTX-A activity did not occur in thalamus, hypothalamus and sensory cortex. BTX-A reduced the neuronal c-Fos activation evoked by facial pain in medullary dorsal horn, but not in thalamus, hypothalamus and amygdala. These results demonstrate the transganglionic transport of BTX-A from periphery to central afferent terminals, and suggest that BTX-A presynaptically alters the nociceptive neurotransmission between primary and secondary sensory neurons in the dorsal horn.

Botulinum toxin A; Synaptosomal-associated protein 25; Retrograde axonal transport; trigeminal nucleus caudalis; central afferent terminals; Immunohistochemistry

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