title: Peripheral antinociception of a chalcone, flavokawin B and possible involvement of the nitric oxide/cyclic guanosine monophosphate/potassium channels pathway.
abstract: Previous studies have shown that systemic administration of 6'-hydroxy-2',4'-dimethoxychalcone (flavokawin B, FKB) exerts significant peripheral and central antinociceptive effects in laboratory animals. However, the mechanisms underlying these peripheral and central antinociceptive effects have yet to be elucidated. Therefore, the objective of the present study was to evaluate the participation of nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/potassium (K+) channels pathway in the peripheral antinociception induced by FKB. It was demonstrated that intraplantar (i.pl.) administration of FKB (150, 250, 375 and 500 µg/paw) resulted in dose-dependent peripheral antinociception against mechanical hyperalgesia in carrageenan-induced hyperalgesia test model in rats. The possibility of FKB having either a central or a systemic effect was excluded since administration of FKB into the right paw did not elicit antinociception in the contralateral paw. Furthermore, peripheral antinociception induced by FKB (500 µg/paw) was significantly reduced when L-arginine (25 µg/paw, i.pl.), Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 50 µg/paw, i.pl.), glibenclamide (300 µg/paw, i.pl.), tetraethylammonium (300 µg/paw, i.pl.) and charybdotoxin (3 µg/paw, i.pl.) were injected before treatment. Taken together, our present data suggest that FKB elicits peripheral antinociception when assessed in the mechanical hyperalgesia induced by carrageenan. In addition, it was also demonstrated that this effect was mediated through interaction of the NO/cGMP/K+ channels signaling pathway.
authors.affiliation: Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Malaysia.
authors.forename: Mohd Nasier
authors.initials: MN
authors.lastname: Kamaldin
authors.forename: Muhammad Nadeem
authors.initials: MN
authors.lastname: Akhtar
authors.forename: Azam Shah
authors.initials: AS
authors.lastname: Mohamad
authors.forename: Nordin
authors.initials: N
authors.lastname: Lajis
authors.forename: Enoch Kumar
authors.initials: EK
authors.lastname: Perimal
authors.forename: Ahmad
authors.initials: A
authors.lastname: Akira
authors.forename: Lee
authors.initials: L
authors.lastname: Ming-Tatt
authors.forename: Daud Ahmad
authors.initials: DA
authors.lastname: Israf
authors.forename: Mohd Roslan
authors.initials: MR
authors.lastname: Sulaiman
mesh_terms: D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000494:pharmacology; D002351:Carrageenan / Q000009:adverse effects; D002599:Chalcone / Q000008:administration & dosage / Q000494:pharmacology*; D006152:Cyclic GMP / Q000378:metabolism*; D004195:Disease Models, Animal; D005419:Flavonoids / Q000008:administration & dosage / Q000494:pharmacology*; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000700:Analgesics; D005419:Flavonoids; D026902:Potassium Channel Blockers; D015221:Potassium Channels; C452039:flavokawain B; D009569:Nitric Oxide; D002599:Chalcone; D002351:Carrageenan; D001120:Arginine; D006152:Cyclic GMP