Botulinum neurotoxin serotype A (
BoNT/A) shows antinociceptive properties, and its clinical applications in
pain therapy are continuously increasing.
BoNT/A specifically cleaves SNAP-25, which results in the formation of a non-functional SNARE complex, thereby potently inhibiting the release of
neurotransmitters and
neuropeptides, including those involved in nociception. The aim of the present study was to determine the effects of
BoNT/A (300pg/paw) on
pain-related behavior and the levels of glial markers and
interleukins in the spinal cord and dorsal root ganglia (DRG) after chronic constriction injury (CCI) to the sciatic nerve in rats. Glial activity was also examined after repeated
intraperitoneal injection of
minocycline combined with a single
BoNT/A injection. Our results show that a single intraplantar
BoNT/A injection did not influence motor function but strongly diminished
pain-related behaviors in naïve and CCI-exposed rats. Additionally, microglial inhibition using
minocycline enhanced the
analgesic effects of
BoNT/A. Western blotting results suggested that CCI induces the upregulation of the pronociceptive
proteins IL-18,
IL-6 and IL-1β in the ipsilateral lumbar spinal cord and DRG, but no changes in the levels of the antinociceptive
proteins IL-18BP,
IL-1RA and
IL-10 were observed. Interestingly,
BoNT/A injection suppressed the CCI-induced upregulation of
IL-18 and IL-1β in the spinal cord and/or DRG and increased the levels of
IL-10 and
IL-1RA in the DRG. In summary, our results suggest that
BoNT/A significantly attenuates
pain-related behavior and microglial activation and restores the neuroimmune balance in a CCI model by decreasing the levels of pronociceptive factors (IL-1β and IL-18) and increasing the levels of antinociceptive factors (IL-10 and IL-1RA) in the spinal cord and DRG.