• Biomolecules & Therapeutics
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• v.3 no.1
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• pp.54-57
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• 1995

The effect of Ruthenium Red on the antinociceptive action of capsaicinoids was investigated using tail-flick test in mice. Capsaicin and KR-25018, when administered subcutaneously, had a potent antinociceptive effect against noxious heat stimulus. Ruthenium Red which is known to block the calcium channel coupled to the capsaicin receptor, when injected intraperitoneally more than 5 mg/kg, showed severe sedation and apparent antinociceptive effect against noxious heat stimulus. The 2.5 mg/kg Ruthenium Red, at which dose any significant sedative effect was not shown, had no effect on the antinociceptive effects of capsaicin and KR-25018. Considering this result, the antinociceptive effect of capsaicinoid may not be related to the Ruthenium Red sensitive calcium channel which is activated by capsaicin.

• The Korean Journal of Pain
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• v.37 no.1
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• pp.26-33
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• 2024

Background: Sitagliptin is an antidiabetic drug that inhibits dipeptidyl peptidase-4 enzyme. This study aimed to investigate the antinociceptive and anti-inflammatory effects of sitagliptin in formalin and carrageenan tests and determine the possible mechanism(s) of its antinociceptive activity. Methods: Male Swiss mice (25-30 g) and male Wistar rats (180-220 g) were used for formalin and carrageenan tests, respectively. In the formalin test, paw licking time and in the carrageenan test, paw thickness were considered as indexes of pain behavior and inflammation respectively. Three doses of sitagliptin (2.5, 5, and 10 mg/kg) were used in these tests. Also, several antagonists and enzyme inhibitors were used to evaluate the role of adrenergic, serotonergic, dopaminergic, and opioid receptors as well as the NO/cGMP/K_ATP pathway in the antinociceptive effect of sitagliptin (5 mg/kg). Results: Sitagliptin showed significant antinociceptive and anti-inflammatory effects in the formalin and carrageenan tests respectively. In the carrageenan test, all three doses of sitagliptin significantly (P < 0.001) reduced paw thickness. Pretreatment with yohimbine, prazosin, propranolol, naloxone, and cyproheptadine could not reverse the antinociceptive effect of sitagliptin (5 mg/Kg), which indicates that adrenergic, opioid, and serotonin receptors (5HT₂) are not involved in the antinociceptive effects. L-NAME, methylene blue, glibenclamide, ondansetron, and sulpiride were able to reverse this effect. Conclusions: NO/cGMP/K_ATP, 5HT₃ and D₂ pathways play an important role in the antinociceptive effect of sitagliptin. Additionally significant anti-inflammatory effects observed in the carrageenan test might contribute in reduction of pain response in the second phase of the formalin test.

• Advances in Traditional Medicine
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• v.7 no.5
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• pp.485-493
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• 2008

The present study was carried out to elucidate the potential of, chloroform extract of Pandanus (P.) fascicularis Lamk (Family-Pandanaceae) leaves on antinociceptive, behavioral study and anti-inflammatory effects using various animal models The dried, powdered leaves of, P. fascicularis were extracted successively with petroleum ether ($60\;-\;80^{\circ}C$) and chloroform in soxhlet apparatus. The chloroform extract (yield 21.6% w/w with respected to dry powdered plant material) was selected for all experimental procedure. Two models were employed to investigate the effects on nociception, the tail immersion and hot plate method in Swiss albino mice and anti inflammatory effect were investigated by employing the carrageenan induced rat paw edema test in. adult Wister albino rats. Behavioral study was investigated by elevated plus maze method in Swiss albino mice. Results were revealed that the PFCE was found significant antinociceptive effect (P < 0.001) at the dose levels of 100, 200 and 400 mg/kg, orally in mice and produced remarkable antiinflammatory effect (P < 0.001) at the same dose levels used in the rats. Behavioral study of the PFCE has no significant anxiolysis effect when used orally. It concludes that, PFCE possessed remarkable antinociceptive effect and anti-inflammatory effect but no anxiolytic effect on animal models.

• The Korean Journal of Pain
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• v.27 no.1
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• pp.23-29
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• 2014

Background: Nefopam has shown an analgesic effect on acute pain including postoperative pain. The reuptake of monoamines including serotonin and noradrenaline has been proposed as the mechanism of the analgesic action of nefopam, but it remains unclear. Although alpha-adrenergic agents are being widely used in the perioperative period, the role of noradrenergic modulation in the analgesic effect of nefopam has not been fully addressed. Methods: Changes in the antinociceptive effect of intrathecal (i.t.) nefopam against formalin-elicited flinching responses were explored in Sprague-Dawley rats pretreated with i.t. 6-hydroxydopamine (6-OHDA), which depletes spinal noradrenaline. In addition, antagonism to the effect of nefopam by prazosin and yohimbine was evaluated to further elucidate the antinociceptive mechanism of i.t. nefopam. Results: Pretreatment with i.t. 6-OHDA alone did not alter the flinching responses in either phase of the formalin test, while it attenuated the antinociceptive effect of i.t. nefopam significantly during phase 1, but not phase 2. The antagonist of the alpha-2 receptor, but not the alpha-1 receptor, reduced partially, but significantly, the antinociceptive effect of i.t. nefopam during phase 1, but not during phase 2. Conclusions: This study demonstrates that spinal noradrenergic modulation plays an important role in the antinociceptive effect of i.t. nefopam against formalin-elicited acute initial pain, but not facilitated pain, and this action involves the spinal alpha-2 but not the alpha-1 receptor.

• The Korean Journal of Pain
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• v.35 no.4
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• pp.440-446
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• 2022

Background: The authors showed in a previous study that some novel triazine derivatives had an anti-inflammatory effect. The present study was designed to evaluate the antinociceptive effect of five out of nine compounds including two vanillintriazine (5c and 5d) and three phenylpyrazole-triazine (10a, 10b, 10e) derivatives which showed the best anti-inflammatory effect. Methods: Male Swiss mice (25-30 g) were used. To assess the antinociceptive effect, acetic acid-writhing, formalin, and hot plate tests were used after intraperitoneal injection of each compound. Results: All compounds significantly (P < 0.001) reduced acetic acid-induced writhing at tested doses (50, 100, and 200 mg/kg). Also, the percent inhibition of writhing in the acetic acid test showed that at the maximum tested dose of these compounds (200 mg/kg), the order of potencies is as follows: 10b > 10a > 10e > 5d > 5c. In the formalin test, compounds 5d, 10a, and 10e showed an antinociceptive effect in the acute phase and all compounds were effective in the chronic phase. In the hot plate test, compounds 5c, 5d, and 10a demonstrated an antinociceptive effect. Conclusions: The results clearly showed that both vanillin-triazine and phenylpyrazole-triazine derivatives had an antinociceptive effect. Also, some compounds which showed activity in the early phase of formalin test as well as in the hot plate test could control acute pain in addition to chronic or inflammatory pain.

• Korean Journal of Plant Resources
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• v.23 no.6
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• pp.513-518
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• 2010

In the present study, the antinociceptive profiles of Dianthus chinensis L extract were examined in ICR mice. Dianthus chinensis L extract administered orally (200 mg/kg) showed an antinociceptive effect as measured by the tail-flick and hot-plate tests. In addition, Dianthus chinensis L extract attenuated the writhing numbers in the acetic acid-induced writhing test. Furthermore, the cumulative nociceptive response time for intrathecal (i.t.) injection of substance P ($0.7\;{\mu}g$) was diminished by Dianthus chinensis L extract. Intraperitoneal (i.p.) pretreatment with yohimbine ($\alpha_2$-adrenergic receptor antagonist) attenuated antinociceptive effect induced by Dianthus chinensis L extract in the writhing test. However, naloxone (opioid receptor antagonist) or methysergide (5-HT serotonergic receptor antagonist) did not affect antinociception induced by Dianthus chinensis L extract in the writhing test. Our results suggest that Dianthus chinensis L extract shows an antinociceptive property in various pain models. Furthermore, this antinociceptive effect of Dianthus chinensis L extract may be mediated by $\alpha_2$-adrenergic receptor, but not opioidergic and serotonergic receptors.

• The Korean Journal of Pain
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• v.19 no.2
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• pp.142-145
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• 2006

Background: Nitric oxide (NO) is involved in the transmission and modulation of nociceptive information at the peripheral, spinal cord and supraspinal levels. We conducted this experiment to assess the antinociceptive effects of a nonselective nitric oxide synthase (NOS) inhibitor, N-nitro-L-arginine methyl ester (L-NAME), on the modulation of pain in rats subjected to the formalin test. Methods: Formalin 5% was injected in the right hind paw after intraperitoneal (IP) injection of various doses of L-NAME (0.5 mg/kg, 1.5 mg/kg with and without L-arginine 100 mg/kg, 5.0 mg/kg). The number of flinches was measured. Results: Formalin injected into the rat hind paw induced a biphasic nociceptive behavior. IP injected L-NAME diminished the nociceptive behaviors in a dose-dependent manner during phases 1 and 2. The concomitant injection of L-arginine reversed the antinocipetive effect of L-NAME. Conclusions: The data demonstrates that a nonselective NOS inhibitor, L-NAME, possesses antinociceptive properties in rats subjected to the formalin test, and the antinociceptive effect of L-NAME is reversed by the concomitant administration of L-arginine.

• Biomolecules & Therapeutics
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• v.5 no.2
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• pp.211-214
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• 1997

In the present study, we investigated the mechanisms of antinociceptive effect and thermoregulatory action of capsaicin in guinea pigs. The administration of capsaicin (5 mg/kg, s.c.) caused a significant decrease in frequency of eye wiping, an indicative of nociceptive threshold. This antinociceptive effect of calsaicin was abolished by co-administration of capsazepine (30 mg/kg, s.c.) with capsaicin, suggesting the involvement of a vanilloid receptor in the antinociceptive action of capsaicin. The administration of capsaicin (1 mg/kg, s.c.) produced a significant decrease in body temperature of guinea pigs. The maximum decrease in body temperature by 2 degrees was shown 1 hour after the treatment, and this decrease was not reversed by coadministration of capsazepine. In conclusion, it is suggested that the mechanism of action of capsaicin-induced thermoregulation involves different pathways from that of capsaicin-induced antinociception.

• Natural Product Sciences
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• v.9 no.2
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• pp.91-92
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• 2003

The present investigation was carried out to evaluate the antinociceptive and sedative - hypnotic effect of a vacuum dried methanol extract of aerial parts of Artemisia pallens. In the tail-flick method with Swiss albino mice the methanol extract at the doses of (1500 mg/kg, 2000 mg/kg, and 2500 mg/kg) showed significant antinociceptive activity. Significant potentiation of Pentobarbitone sodium - induced sleeping time was observed in mice on co-administration of the various doses of the methanol extract of Artemisia pallens.

• The Korean Journal of Pain
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• v.25 no.4
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• pp.221-227
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• 2012

Background: It has been reported that curcumin, the main active compound of Curcuma longa, also known as turmeric, exhibits antinociceptive properties. The aim of this study was to examine the participation of ATP-sensitive potassium channels ($K_{ATP}$ channels) and, in particular, that of the L-arginine-nitric oxide-cyclic GMP-$K_{ATP}$ channel pathway, in the antinociceptive effect of curcumin. Methods: Pain was induced by the intraplantar injection of 1% formalin in the right hind paw of Wistar rats. Formalin-induced flinching behavior was interpreted as an expression of nociception. The antinociceptive effect of oral curcumin was explored in the presence and absence of local pretreatment with L-NAME, an inhibitor of nitric oxide synthase, ODQ, an inhibitor of soluble guanylyl cyclase, and glibenclamide, a blocker of $K_{ATP}$ channels. Results: Oral curcumin produced a dose-dependent antinociceptive effect in the 1% formalin test. Curcumin-induced antinociception was not altered by local L-NAME or ODQ, but was significantly impaired by glibenclamide. Conclusions: Our results confirm that curcumin is an effective antinociceptive agent. Curcumin-induced antinociception appears to involve the participation of $K_{ATP}$ channels at the peripheral level, as local injection of glibenclamide prevented its effect. Activation of $K_{ATP}$ channels, however, does not occur by activation of the L-arginine-nitric oxide-cGMP-$K_{ATP}$ channel pathway.