Objective and design: We previously described the visceral antinociceptive property of alpha, beta-amyrin in a mouse model of cystitis induced by cyclophosphamide (CPM). This study examined the contribution of vanilloid-1 (TRPV1), peripheral NK1 receptors to CPM-evoked nociceptive behaviors and bladder edema, and its possible modulation by alpha, beta-amyrin.
Methods: The effect of alpha, beta-amyrin (10, 30, and 100 mg/kg, p. o.) and N-acetylcysteine (NAC) on CPM (400 mg/kg, i. p.)-induced cystitis was studied in mice. Sensory deafferentation was done by a high dose capsaicin. The parameters analysed were: CPM-evoked noxious behaviors, bladder edema, vascular permeability, and NK(1) immunoreactivity. To assess the role of K(+) (ATP) channels in alpha, beta-amyrin effect, animals were pretreated with glibenclamide.
Results: alpha, beta-amyrin (30 and 100 mg/kg) and NAC significantly (p < 0.01) suppressed the visceral pain-related behaviors and NK(1) immunoreactivity, but bladder edema was reduced weakly. Glibenclamide reversed the effects of alpha, beta-amyrin. Sensory deafferentation by capsaicin significantly reduced the nociceptive responses and the NK(1) immunoreactivity to noxious stimulation by CPM.
Conclusions: alpha, beta-amyrin attenuates CPM-induced visceral pain and bladder edema by mechanisms that involve, at least in part, a block either of Substance P release or its receptor function, and partly by opening K(+) (ATP) channels.