Zerumbone-induced antinociception: involvement of the L-arginine-nitric oxide-cGMP -PKC-K+ ATP channel pathways.

This study investigated the antinociceptive effects of zerumbone in chemical behavioural models of nociception in mice. Zerumbone given through intraperitoneal route (i.p.) produced dose-related antinociception when assessed on acetic acid-induced abdominal writhing test in mice. In addition, the i.p. administration of zerumbone exhibited significant inhibition of the neurogenic pain induced by intraplantar (i.pl.) injection of capsaicin and bradykinin. Likewise, zerumbone given by i.p. route reduced the nociception produced by i.pl. injection of glutamate and phorbol myristate acetate (PMA). The antinociception caused by zerumbone in the acetic acid test was significantly attenuated by i.p. pre-treatment of mice with l-arginine (nitric oxide precursor) and glibenclamide (ATP-sensitive K(+) channel inhibitor). However, the antinociception of zerumbone was enhanced by methylene blue (non-specific gyanylyl cyclase inhibitor). Together, these results indicate that zerumbone produces pronounced antinociception against chemical models of nociception in mice. It also strongly suggests that the l-arginine-nitric oxide-cGMP-PKC-K(+) ATP channel pathways, the TRPV1 and kinin B2 receptors play an important role in the zerumbone-induced antinociception

Involvement of opioid receptors in Boesenbergia pandurata's esssential oil (BPEO)-induced antinociceptive activity in animal model of nociception

Boesenbergia pandurata is a folklore remedy for relieving stomach, abdominal, joint, and muscular pain. Previous study from our research group has shown that Boesenbergia pandurata’s essential oil (BPEO) possesses antinociceptive activity against chemical and thermal models of pain. The present study was conducted to evaluate participation of opioid receptors in BPEO-induced antinociceptive activity. The involvement opioid receptors were assessed using acetic acid-induced abdominal writhing test. The acetic acid-induced writhing test was conducted by administering the non-selective opioid receptor antagonists (naloxone) 15 minutes before administration of BPEO orally, and selective opioid receptor antagonists (beta-funaltrexamine, norbinaltorphimine, and naltrindole) 1 day before BPEO administration. 0.6% acetic acid was later injected intraperitoneally and 5 minutes after the injection mice was observed for writhing response in 30 minutes time span. It was demonstrated that oral administration of BPEO 300 mg/kg produced 82.19% inhibition of nociception induced by 0.6% acetic acid injection. Opioid receptor antagonists administration solely did not modify acetic acid-induced nociceptive behavior. However, administration of naloxone (non-selective opioid antagonist) significantly increases the nociceptive response of animal receiving BPEO in the acetic acid-induced writhing test. Furthermore, administration of beta-funaltrexamine (mu opioid receptor antagonist and norbinaltorphimine kappa opioid receptor antagonist) significantly reserved antinociceptive activity induced by BPEO. Together, these result suggested participation of opioid receptors in inducing antinociceptive in animal model. In conclusion, BPEO may exert its antinociceptive activity through activation of mu opioid receptor, as well as kappa opioid receptor

Peripheral Antinociception of a Chalcone, Flavokawin B and Possible Involvement of the Nitric Oxide/Cyclic Guanosine Monophosphate/Potassium Channels Pathway

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Peripheral Antinociception of a Chalcone, Flavokawin B and Possible Involvement of the Nitric Oxide/Cyclic Guanosine Monophosphate/Potassium Channels Pathway

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