Antinociceptive effect of botulinum toxin A involves alterations in AMPA receptor expression and glutamate release in spinal dorsal horn neurons

- BTX-A could retrograde axonal transport to the dorsal horn after peripheral application.
- BTX-A could decrease the expression and function of AMPA receptor in dorsal horn neurons.
- Pretreatment with BTX-A decrease formalin-evoked release of glutamate in dorsal horn neurons.

The use of botulinum toxin A (BTX-A) for various clinical therapeutic applications is increasing. It is widely believed that peripheral therapeutic or toxic effects of BTX-A are exclusively mediated by SNAP-25 cleavage. There is growing evidence of long-distance retrograde axonal transport of BTX-A on entering the central nervous system, subsequent to a local injection of the toxin. However, the prevalence of central antinociceptive effects after BTX-A peripheral application and its underlying mechanisms are unclear. Our results show that (1) BTX-A can undergo retrograde axonal transport to the dorsal horn after peripheral application; (2) Peripheral pretreatment with BTX-A decreases the expression and function of AMPA receptors in the spinal cord dorsal horn neurons; (3) Peripheral pretreatment with BTX-A does not change basal glutamate release, but decreases the effect of formalin-evoked release of glutamate in spinal cord dorsal horn neurons. These results suggest that peripheral application of BTX-A can change AMPA receptor expression in, and glutamate release from, spinal dorsal horn neurons, which may have significance in its central antinociceptive effects.