• International Journal of Oral Biology
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• v.32 no.2
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• pp.59-65
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• 2007

It has been well known that excitatory amino acids, primarily glutamate, are involved in the transmission of nociception in pathological and physiological conditions in the spinal and brainstem level. Recently, peripheral glutamate also play a critical role in the peripheral nociceptive transmissions. The present study investigated the role of N-methyl-D-aspartic acid (NMDA) or non-NMDA ionotropic glutamate receptors in formalin-induced TMJ pain. Experiments were carried out on male Sprague-Dawley rats weighing 220-280 g. Intra-articular injection was performed under halothane anesthesia. Under anesthesia, AP-7 (10, $100\;{\mu}M$, $1\;mM/20\;{\mu}L$), a NMDA receptor antagonist, or CNQX disodium salt (0.5, 5, 50, $500\;{\mu}M/20\;{\mu}L$), a non-NMDA receptor antagonist, were administered intra-articularly 10 min prior to the application of 5% formalin. For each animal, the number of behavioral responses, such as rubbing and/or scratching the TMJ region, was recorded for nine successive 5-min intervals. Intra-articular pretreatment with 1 mM of AP-7 or $50\;{\mu}M$ CNQX significantly decreased the formalin-induced scratching behavioral responses during the second phase. Intra-articular pretreatment with $500\;{\mu}M$ of CNQX significantly decreased the formalin-induced scratching behavior during both the first and the second phase. These results indicate that the intra-articular administration of NMDA or non-NMDA receptor antagonists inhibit formalin-induced TMJ nociception, and peripheral ionotropic glutamate receptors may play an important role in the TMJ nociception.

• 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.

• The Korean Journal of Pain
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• v.23 no.4
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• pp.236-241
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• 2010

Background: Selective inhibitors of cycloosygenase (COX)-2 are commonly used analgesics in various pain conditions. Although their actions are largely thought to be mediated by the blockade of prostaglandin (PG) biosynthesis, evidences suggesting endogenous opioid peptide link in spinal antinociception of COX inhibitor have been reported. We investigated the roles of opioid receptor subtypes in the spinal antionociception of selective COX-2 inhibitor. Methods: To examine the antionociception of a selective COX-2 inhibitor, DUP-697 was delivered through an intrathecal catheter, 10 minutes before the formalin test in male Sprague-Dawley rats. Then, the effect of intrathecal pretreatment with CTOP, naltrindole and GNTI, which are ${\mu}$, $\delta$, and k opioid receptor antagonist, respectively, on the analgesia induced by DUP-697 was assessed. Results: Intrathecal DUP-697 reduced the flinching response evoked by formalin injection during phase 1 and 2 Naltrindole and GNTI attenuated the antinociceptive effect of intrathecal DUP-697 during both phases of the formalin test, CTOP reversed the antinociception of DUP-697 during phase 2, but not during phase 1, Conclusions: Intrathecal DUP-697, a selective COX-2 inhibitor, effectively relieved inflammatory pain in rats. The $\delta$ and $\kappa$ opioid receptors are involved in the activity of COX-2 inhibitor on the facilitated state as well as acute pain at the spinal level, whereas the ${\mu}$ opioid receptor is related only to facilitated pain.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.15 no.1
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• pp.316-322
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• 2014

The present study investigated the inflammatory hypersensitivity following activation of the transient receptor potential vanilloid receptor-1(TRPV1) in rats. Experiments were carried out on male Sprague-Dawley rats weighing 220-260g. Following an subcutaneous injection of 5% formalin in the orofacial area, nociceptive scratching behavior was recorded for 9 successive 5-min intervals in rats. The subcutaneous injection of $25{\mu}L$ of 5% formalin produced noxious scratching behavior. Injection of capsaicin, TRPV1 agonist, alone into the vibrissa pad did not produced nociceptive behavior. After subcutaneous injection of capsaicin(0$0.1{\mu}g$, $1{\mu}g/10{\mu}L$) in the formalin-treated rats, nociceptive scratching behavior was recorded for 9 successive 5-min internals. Injection of capsaicin into the vibrissa pad significantly increased the number of scratches at 1 hours after injection. Noxious behavioral responses induced by subcutaneous capsaicin injection were significantly potentiated in formalin-treated rats. Pre or post-treatment with iodo-resinaferatoxin(IRTX), TRPV1 antagonist, significantly attenuated increased nociceptive behavior. These findings suggest that activation of the TRPV1 enhanced formalin-induced inflammatory pain in the orofacial area of rats.

• The Korean Journal of Pain
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• v.24 no.4
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• pp.179-184
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• 2011

Background: The analgesic mechanisms of cyclooxygenase (COX)-2 inhibitors have been explained mainly on the basis of the inhibition of prostaglandin biosynthesis. However, several lines of evidence suggest that their analgesic effects are mediated through serotonergic or adrenergic transmissions. We investigated the roles of these neurotransmitters in the antinociception of a selective COX-2 inhibitor at the spinal level. Methods: DUP-697, a selective COX-2 inhibitor, was delivered through an intrathecal catheter to male Sprague-Dawley rats to examine its effect on the flinching responses evoked by formalin injection into the hindpaw. Subsequently, the effects of intrathecal pretreatment with dihydroergocristine, prazosin, and yohimbine, which are serotonergic, ${\alpha}1$ adrenergic and ${\alpha}2$ adrenergic receptor antagonists, respectively, on the analgesia induced by DUP-697 were assessed. Results: Intrathecal DUP-697 reduced the flinching response evoked by formalin injection during phase 1 and 2. But, intrathecal dihydroergocristine, prazosin, and yohimbine had little effect on the antinociception of intrathecal DUP-697 during both phases of the formalin test. Conclusions: Intrathecal DUP-697, a selective COX-2 inhibitor, effectively relieved inflammatory pain in rats. Either the serotonergic or adrenergic transmissions might not be involved in the analgesic activity of COX-2 inhibitors at the spinal level.

• Journal of Acupuncture Research
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• v.34 no.2
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• pp.61-74
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• 2017

Objectives : This study was carried out to evaluate analgesic effects of Zanthoxylum bungeanum Maxim (ZM) pharmacopuncture on formalin-induced pains in Sprague-Dawley (SD) rats and ICR-mice. Methods : The subjects were divided 8 weeks aged rats with constant pain sensitivity into five groups; normal (treated with normal saline at Taegye (KI3) and before injected with normal saline at hindpaw), Con-1 (treated with normal saline at KI3 before injected with formalin at hindpaw), Lido-1 (treated with lidocaine at KI3), ZMWG-1 (treated with Hot water extraction pharmacopuncture of Zanthoxylum bungeanum Maxim at KI3), ZMEG-1 (treated with ethanol extraction pharmacopuncture of Zanthoxylum bungeanum Maxim at KI3). After 35 minutes, we measured ultrasonic vocalization (USV) and enzyme activities of both Aspartate aminotransferase (AST), Alanine aminotransferase (ALT) in rat serum. In addition, Tail flick test is performed by injecting ICR mice at 5 weeks of age. And it classified into 4 groups (Con-2, Lido-2, ZMWG-2, ZMEG-2) according to the kind of drug (normal saline, lidocaine, ZMW, ZME). After each drug injection, we examined the reaction by placing the tail in water at $50^{\circ}C$. Results : ZME had analgesic effects in the early and late phase of USV during the formalin test. There were no significant differences between ZMEG-1 and Lido-1 in early and late phase of USV. Also, No significant differences observed in serum AST and ALT activity in ZMWG-1 and ZMEG-1 compared with Con-1. For tail-flick test, analgesic effect on warmth significantly increased in Lido-2 and ZMEG-2 compare to that of Con-2. Conclusion : ZME pharmacopuncture had analgesic effects on formalin-induced pain without liver toxicity. Also, tail-flick test suggest that ZME pharmacopuncture could be useful technique on analgesic effect on warmth and treatment of pains.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.15 no.9
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• pp.5708-5715
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• 2014

The effects of korean red ginseng (KRG) extracts on orifacial pain control in terms of the systemic inflammatory response and pharmacological effects as health supplements were investigated. The experimental group were divided into three groups, the control group (n=6), formalin (5%, $50{\mu}{\ell}$) injection group (n=6), and formalin (5%, $50{\mu}{\ell}$) injection added KRG administrated group (4.5 ml/kg, n=6). The KRG administrated group prior to the formalin injection significantly attenuated the behavioral response compared to that of the control group. Pain reduction was suppressed mainly from 15 min to 30 min. The KRG administrated rats showed significantly reduced p38 MAPK, iNOS and Nrf2 expression in the brain and medulla oblongata according to Western blot analysis. These findings suggest that KRE may have a useful effect on orificial pain control functions by preventing the p38 MAPK pathway.

• Advances in Traditional Medicine
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• v.9 no.3
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• pp.232-237
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• 2009

The effect of arogh, a polyherbal formulation-PHF [each 3 g powder contained Nelumbo nucifera G. (0.24 g), Hemidesmus indicus R. (0.24 g), Zingiber officinale R. (0.24 g), Terminalia chebula R. (0.24 g), Quercus infectoria O. (0.12 g), Hibiscus rosa-sinensis L. (0.24 g), Rosa damascene M.(0.24 g), Eclipta alba H.(0.24 g), Glycyrrhiza glabra L. (0.24 g)] was investigated in various experimental models of pain and inflammation. Analgesic activity of PHF was studied in mice using acetic acid induced writhing, tail immersion and hot plate methods. Anti-inflammatory activity of PHF was studied in rats using carrageenan induced hind paw edema and formalin induced rat paw edema methods. PHF significantly (P < 0.05) reduced the number of writhings, increased latency to flick tail in tail immersion method and elevated the mean basal reaction time in hot plate method. PHF significantly (P < 0.05) inhibited carrageenan induced hind paw edema and formalin induced rat paw edema. The PHF was tested at dose of 30, 100, 300 and 500 mg/kg.

• Biomolecules & Therapeutics
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• v.5 no.2
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• pp.117-124
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• 1997

The analgesic effects of DA-5018, a new caosaucin derivative, were evaluated in various experimental pain models. Drugs were administered subcutaneously or topically. When drugs were administered subcutaneously, 1) the $ED_{50}$ of DA-5018, morphine . HCI, capsaicin and acetaminophen were 0.091-2.0, 0.3-4.3, 1.4-26.5 and 45.4-643 mg/kg, respectively in various pain or inflammatory models including acetic acid writhing, formalin, tail flick, Randall-Selitto, hot plate and crouton oil-induced ear edema test, 2) the AD2 values (the dose for doubling of pain threshold of vehicle control) of DA-5018, capsaicin and ketoprpgin were 1.07 $\pm$ 0. 18, 23.47$\pm$4.46 and 2.97$\pm$0.43 mg/kg in Freund's complete adjuvant (FCA)-induced arthritic pain model. And by topical application, 1) neither DA-5018 0.3% cream nor Zostrix-HP (capsaicin 0.075%) were effective in formalin test, 2) although DA-5018 0.3% cream significantly inhibited the croton oil-induced ear edema being better than Zostrix-HP and Kenofen (ketoprofen 3%). 3) In FCA model, DA-5018 0.3% cream reversed the decreased pain threshold of arthritic rat from 136.4 g (day 0) to 289.0 g (day 5) and 250.1 g (day 10), which was similar to Zostrix-HP. These results suggest that DA-5018 administered subcutaneously has a potent and broad analgesic spectrum than nonsteroidal antiinflammatory drugs against acute and chronic pain, and by topical application it exerts comparable analgesic and antiinglammaatory effects to capsaicin cream.

• The Korean Journal of Pain
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• v.37 no.2
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• pp.141-150
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• 2024

Background: Stingless bee propolis is a popular traditional folk medicine and has been employed since ancient times. This study aimed to evaluate the antinociceptive activities of the chemical constituents of aqueous propolis extract (APE) collected by Trigona thoracica in a nociceptive model in mice. Methods: The identification of chemical constituents of APE was performed using high-performance liquid chromatography (HPLC). Ninety-six male Swiss mice were administered APE (400 mg/kg, 1,000 mg/kg, and 2,000 mg/kg) before developing nociceptive pain models. Then, the antinociceptive properties of each APE dose were evaluated in acetic acid-induced abdominal constriction, hot plate test, and formalin-induced paw licking test. Administration of normal saline, acetylsalicylic acid (ASA, 100 mg/kg, orally), and morphine (5 mg/kg, intraperitoneally) were used for the experiments. Results: HPLC revealed that the APE from Trigona thoracica contained p-coumaric acid (R² = 0.999) and caffeic acid (R² = 0.998). Although all APE dosages showed inhibition of acetic acid-induced abdominal constriction, only 2,000 mg/kg was comparable to the result of ASA (68.7% vs. 73.3%, respectively). In the hot plate test, only 2,000 mg/kg of APE increased the latency time significantly compared to the control. In the formalin test, the durations of paw licking were significantly reduced at early and late phases in all APE groups with a decrease from 45.1% to 53.3%. Conclusions: APE from Trigona thoracica, containing p-coumaric acid and caffeic acid, exhibited antinociceptive effects, which supports its potential use in targeting the prevention or reversal of central and peripheral sensitization that may produce clinical pain conditions.