Modulation of acute visceral nociception and bladder inflammation by plant triterpene, alpha, beta-amyrin in a mouse model of cystitis: role of tachykinin NK(1)-receptors, and K(+)(ATP) channels.
OBJECTIVE
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.
Lima-Júnior
R C P
RC
Departamento de Fisiologia e Farmacologia, Universidade Federal do Ceará, Campus do Porangabussu, Fortaleza, Ceará, Brazil.
Sousa
D I M
DI
Brito
G A C
GA
Cunha
G M
GM
Chaves
M H
MH
Rao
V S N
VS
Santos
F A
FA
D000111:Acetylcysteine / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D002211:Capsaicin / Q000494:pharmacology; D003520:Cyclophosphamide; D003556:Cystitis / Q000139:chemically induced / Q000188:drug therapy*; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D005905:Glyburide / Q000494:pharmacology; D054086:KATP Channels / Q000502:physiology*; D008297:Male; D051379:Mice; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology*; D018040:Receptors, Neurokinin-1 / Q000502:physiology*; D050916:TRPV Cation Channels / Q000502:physiology*; D001743:Urinary Bladder / Q000187:drug effects / Q000503:physiopathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D054086:KATP Channels; D018040:Receptors, Neurokinin-1; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D009828:Oleanolic Acid; D003520:Cyclophosphamide; C036380:beta-amyrin; D002211:Capsaicin; D005905:Glyburide; D000111:Acetylcysteine