Lack of anti-inflammatory effect of botulinum toxin type A in experimental models of inflammation

Botulinum toxin type A (BTX-A) has a long-lasting antinociceptive activity and less clear effect on inflammation. It was proposed that these two effects share the same mechanism - the inhibition of neurotransmitter exocytosis from peripheral nerve endings. However, till now possible anti-inflammatory action of BTX-A did not evoke much attention. In the present paper, we investigate possible anti-inflammatory action of the toxin in carrageenan and capsaicin models of inflammation in rats. BTX-A (5 and 10 U/kg) was injected into the plantar surface of the rat right hind-paw pad 5 days before the injection of the carrageenan (1%) or capsaicin (0.1%) at the same site. Carrageenan-induced paw oedema and capsaicin-induced protein extravasation were measured. Control, inflamed and BTX-A pretreated inflamed paws were photographed and histopathological analysis (haematoxylin & eosin) was performed. Pretreatment with BTX-A had no effect on the size of carrageenan-induced paw oedema, measured as paw volume and weight or capsaicin-induced plasma extravasations, measured by Evans blue as a marker of protein leakage. Neither macroscopic nor microscopic analysis showed a significant difference between BTX-A pretreated and control inflamed tissue. Results show dissociation between the effect of BTX-A on pain and inflammation thus questioning the validity of the suggested assumption about the common peripheral mechanism of action.