Review of a proposed mechanism for the antinociceptive action of botulinum toxin type A

Botulinum toxin type A (BOTOX (R)) has been used to treat pathological pain conditions although the mechanism is not entirely understood. Subcutaneous (s.c.) BOTOX (R) also inhibits inflammatory pain in the rat formalin model, and the present study examined whether this could be due to a direct action oil sensory, neurons. BOTOX (R) (3.5-30 U/kg) was injected s.c. into the subplantar surface of the rat hind paw,followed 1-5 days later by 50 mL of 5% formalin. Using microdialysis, we found that BOTOX (R) significantly inhibited formalin-induced glutamate release (peak inhibitions: 35%, 41%, and 45% with 3.5, 7, and 15 U/kg, respectively). BOTOX (R)) also dose dependently reduced the number of formalin-induced Fos-like immunoreactive cells in the dorsal horn of the spinal cord and significantly (15 and 30 U/kg) inhibited the excitation of wide dynamic range neurons of the dorsal horn in Phase II but not Phase I of the formalin response. These results indicate that s.c. BOTOX (R) inhibits neurotransinitter release from primary sensory neurons in the rat formalin model. Through this mechanism, BOTOX (R) inhibits peripheral sensitization in these models, which leads to all indirect reduction in central sensitization. (R) 2005 Elsevier Inc. All rights reserved.