Mechanisms of the antinociceptive effect of subcutaneous BOTOX®: inhibition of peripheral and central nociceptive processing

Abstract Botulinum toxin type A (BoNT-A; BOTOX®) has been used for the treatment of conditions involving excessive muscle contractions, as well as painful pathological conditions such as low back pain, headache, myofascial pain, and migraine. Our group has demonstrated that subcutaneous (SC) BOTOX® inhibits inflammatory pain in the rat formalin model, suggesting a direct action on sensory neurones. However, direct evidence that BOTOX® produces pain relief by inhibiting the release of neurotransmitters from sensory neurones in an animal model of pain is lacking. The present study was therefore designed to investigate this possibility using the rat formalin model, examining the effects of BOTOX® on (1) formalin induced glutamate release, (2) the pattern of formalin-induced Fos-like immunoreactivity, and (3) formalin-induced activation of wide dynamic range (WDR) neurones in the dorsal horn.