• Title, Summary, Keyword: Nociception

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TEVC Studies of potent Antagonists of Human $P2X_3$ Receptor

  • Moon, Hyun-Duk;Lee, Jung-Sun;Park, Chul-Seung;Kim, Yong-Chul
    • Proceedings of the Korean Biophysical Society Conference
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    • pp.55-55
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    • 2003
  • P2X$_3$ receptor, a member of P2 purine receptors, is a ligand-gated ion channel activated by extracellular ATP as an endogenous ligand, and highly localized in peripheral and central sensory neurons. The activation of P2X3 receptor by ATP as the pronociceptive effect has been known to initiate the pain signaling involved in chronic inflammatory nociception and neuropathic pain by nerve injury, implicating the possibility of new drug development to control pains. In this study, we have developed a two electrode voltage clamp (TEVC) assay system to evaluate the inhibitory activity of several newly synthesized PPADS and a novel non-ionic antagonist against ATP activation of human P2X3 receptor. PPADS derivatives include several pyridoxine and pyridoxic acid analogs to study the effects of phosphate and aldehyde functional groups in PPADS. All new PPADS analogs were less potent than PPADS at human P2X$_3$ receptors, however, LDD130, a non-ionic analog showed potent antagonistic property with $IC_{50}$/ of 8.34 pM. In order to uncover the structure activity relationships of LDD130, and design new structural analogs, we synthesized and investigated a few structural variants of LDD130, and the results will be discussed in this presentation.

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Melittin-induced Nociceptive Responses are Alleviated by Cyclooxygenase-1 Inhibitor

  • Kim, Joo-Hyun;Shin, Hong-Kee;Lee, Kyung-Hee
    • The Korean Journal of Physiology and Pharmacology
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    • v.10 no.1
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    • pp.45-50
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    • 2006
  • Melittin-induced pain model has been known to be very useful for the study of pain mechanism. Melittin-induced nociceptive responses are reported to be modulated by the changes in the activity of excitatory amino acid receptor, calcium channel, spinal serotonin receptor and extracellular signaling-regulated kinase. The present study was undertaken to investigate the role of cyclooxygenase (COX) in the melittin-induced nociception. Changes in mechanical threshold, flinchings and paw thickness were measured before and after intraplantar injection of melittin in the rat hind paw. Also studied were the effects of intraperitonealy administered diclofenac (25 mg & 50 mg/kg), piroxicam (10 mg & 20 mg/kg) and meloxicam (10 mg & 20 mg/kg) on the melittin-induced nociceptions. Intraplantar injection of melittin caused marked reduction of mechanical threshold that was dose-dependently attenuated by non-selective COX inhibitor (diclofenac) and selective COX-1 inhibitor (piroxicam), but not by COX-2 inhibitor (meloxicam). Melittin-induced flinchings were strongly suppressed by non-selective COX and COX-1 inhibitor, but not by COX-2 inhibitor. None of the COX inhibitors had inhibitory effects on melittin-induced increase of paw thickness (edema). These experimental findings suggest that COX-1 plays an important role in the melittin-induced nociceptive responses.

The Analgesic Effect and Mechanisms of Dianthus chinensis L Extract in the mice.

  • Park, Soo-Hyun;Sim, Yun-Beom;Lee, Jin-Koo;Lim, Soon-Sung;Kim, Jin-Kyu;Suh, Hong-Won
    • 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 Involvement of Protein kinase C in Glutamate-Mediated Nociceptive Response at the Spinal Cord of Rats (흰쥐의 척수에서 Glutamate가 매개하는 Nociceptive Response에 있어서 Protein kinase C의 관련성)

  • 김성정;박전희;이영욱;양성준;이종은;이병천;손의동;허인회
    • YAKHAK HOEJI
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    • v.43 no.2
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    • pp.263-273
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    • 1999
  • When glutamate was infected intrathecally, the result is similar to those produced by TPA injected. The involvement of protein kinase C (PKC) in the nociceptive responses in rat dorsal horn neurons of lumbar spinal cord was studied. In test with formalin, a PKC inhibitor (chelerythrine) inhibited dose-dependently the formalin-induced behavior response. Neomycin also inhibited it significantly. But, a PKC activator (12-O-tetradecanoylphorbol-13-ester, TPA) showed reverse effect. When gluatamate was injected intrathecally, we observed the result is smilar to those produced by TPA injection. On the other hand, intrathecal injection of glutamate induced thermal and mechanical hyperalgesia. In Tail-flick test, we examined the involvement of PKC on the glutamate-indeced thermal hyperalgesia. Chelerythrine showed an inhibitory effect and TPA enhanced thermal response. Glutamate decreased the mechanical threshold significantly. A pretreatment of chelerythrine and neomycin inhibited glutamate-induced mechanical hyperalgesia, but the effect of neomycin was not significant. TPA had little effect on the mechanical nociceptive response. These results suggest that the PKC activation through metabotropic receptor at postsynaptic region of spinal cord dorsal horn neurons may influence on the persistent nociception produced by chemical stimulation with formalin, thermal and mechanical hyperalgesia induced by glutamate.

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Antinociceptive and anti-inflammatory activities of Pandanus fascicularis Lamk. leaves in animal models

  • Panda, Prabhudutta;Panda, DP;Panda, PK;Nayak, SS
    • Oriental Pharmacy and Experimental 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.

Evaluation of the analgesic and anti-inflammatory properties of methanol extract of Artanema sesamoides Benth roots in animal models

  • Gupta, Malaya;Mazumder, UK;Selvan, V Thamil;Manikandan, L;Senthilkumar, GP;Suresh, R;Gomathi, P;Kumar, B Ashok
    • Oriental Pharmacy and Experimental Medicine
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    • v.8 no.2
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    • pp.196-203
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    • 2008
  • The methanol extract of the root of Artanema sesamoides Family Scrophuilariaceae (MEAS) was investigated for possible analgesic and anti-inflammatory effects in animals. Three models were used to study the extract effects on nociception, which were acetic acid-induced writhing response, hot-plate method and the tail flick test in mice. The antiinflammatory effects were evaluated using carrageenan, dextran, histamine and serotonin induced rat paw oedema (acute) and cotton pellet induced granuloma (chronic) models in rats. Results of the study revealed that the extract exhibited significant (P < 0.001) analgesic effect at a dose of 50, 100 and 200 mg/kg b.w p.o in mice in all the models. In acute model, the MEAS also exhibited significant (P < 0.001) antiinflammatory effect in all the above mentioned doses. In chronic model (cotton pellet induced granuloma) the MEAS 200 mg/kg and indomethacin 10 mg/kg showed that inhibition of granuloma formation 25.0% and 47.7% respectively (P < 0.001). The MEAS and indomethacin were effectively preventing the transudation of the fluid. Thus, the present study revealed that the methanol extract of the root of Artanema sesamoides exhibited significant analgesic and antiinflammatory activity.

Analgesic and anti-inflammatory effect of the aqueous extract of Angelica dahurica

  • Choi, In-Ho;Song, Yun-Kyung;Lim, Hyung-Ho
    • The Journal of Korean Medicine
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    • v.29 no.2
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    • pp.32-40
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    • 2008
  • Background: Angelica dahurica has been used in various clinical cases. Its taste is hot and its property is warm, dry and nonpoisonous. Its efficacy is to remove wind-damp, cure swelling and edema, exhaust pus, stop itching, rhinitis and leukorrhea. Object: To test through experiment Angelica dahurica's analgesic and anti-inflammatory efficacy. Method: Inject acetic acid as a pain-inducing substance to the mice and measure visceral pain bywrithing reflex. Inject carrageenan that is an edema-inducing substance to the rat's paw and measure volume of edema. Take thermal pain to mice with plantar test and measure paw withdrawal latency. Normal group is non Angelica dahurica-treated group and treated group is Angelica dahurica-treated group. Results: In acetic acid-induced visceral model, treatment with Angelica dahurica suppressed writhing reflex significantlyand dose-dependently. In carrageenan-induced paw edema model, treatment with Angelica dahurica suppressed carrageenan-induced paw edema. In plantar test model, no significant effect on the withdrawal latency of thermal stimulation-induced nociception was observed. Conclusion: Angelica dahurica has analgesic and anti-inflammatory efficacy.

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A Saponin Complex, KPRG-C, and Its Sapogenin Complex, KPRG-D, Reduce Nociception and Inflammation in Animals

  • Nam, Jung-Hwan;Jung, Hyun-Ju;Choi, Jong-Won;Park, Hee-Juhn
    • Korean Journal of Plant Resources
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    • v.20 no.3
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    • pp.226-233
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    • 2007
  • To develop a clinically available saponin- or sapogenin complex from Oriental medicines, the EtOH extract (KPRG-A) was obtained by extracting from the four crude drugs, Kalopanacis Cortex, Platycodi Radix, Rubi Fructus and Glycyrrhizae Radis. The BuOH fraction (KPRG-B), a crude saponin complex, was prepared by fractionating KPRG-A, which were further completely hydrolyzed to afford the sapogenin complex (KPRG-D). In an attempt to find the antinoicpetive effects of the saponin complex and sapogenin complex, KPRG-C, and -D, were assayed by writhing-, hot plate-, and tail-flick tests using mice or rats. The three samples were also subjected to antiiflammatory tests using serotonin-induced and carrageenan-induced hind paw edema mice and rats, respectively. The three samples significantly reduced inflammations and pains of the experimental animal. The potency were found in the order of KPRG-D> KPRG-C> KPRG-B. The most active sample, KPRG-D, caused no death, no body increase or no anatomical pathlogic change even at 2,000 mg/kg dose. These results suggest that a sapogenin complex, KPRG-D, which was found to contain mainly hederagenin, platycodigenin, polygalacic acid, 23-hydroxytormentic acid, glycyrrhetic acid together with minor triterpene acids, could be a potential candidate for antiinflammatory therapeutics.

Evaluation of the Antinociceptive Properties of GCSB-5, a Herbal Formulation (생약복합제 GCSB-5의 급성통증 모델에서의 진통작용)

  • Lee, Chan-Ho;Kim, Sung-Hwa;Lee, Jun-Seok;Cho, Kang-Hoon;Kim, Jeoung-Seob;Cho, Soon-Hyun;Lee, Sun-Mee
    • Korean Journal of Pharmacognosy
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    • v.36 no.4
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    • pp.299-304
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    • 2005
  • This study examined the antinociceptive properties of GCSB-5, a herbal formulation consisting of 6 Oriental herbs (Ledebouriellae Radix, Achyranthis Radix, Acanthopanacis Cortex, Cibotii Rhizoma, Glycine Semen, and Eucommiae Cortex) that are used in traditional medicine to treat various bone disorders, mainly of which involve analgesic processes. Peripheral and central analgesic models were established in experimental animals in order to evaluate the antinociceptive effects of the agent. GCSB-5 significantly inhibited the number of acetic-induced writhing (33.3%-34.3% inhibition at 100-600 mg/kg) but increased the pain threshold (38.0% increase at 300 mg/kg) in the Randall-Selitto test. However, GCSB-5 had no effect on the hot plate-induced nociception and hyperalgesia from the tail-pinch method. These results suggest that the antinociceptive effect of GCSB-5 may be mediated via peripheral mechanisms.

Effects of Ginsenoside Total Saponins on Experimental Irritable Bowel Syndrome in Rats

  • Kim, Jong-Hoon;Nah, Seung-Yeol
    • Journal of Ginseng Research
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    • v.29 no.2
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    • pp.94-99
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    • 2005
  • In the previous study, we reported that the in viかo inhibitory effect of ginsenosides, active ingredient of Panax ginseng, on $5-HT_{3A}$ receptor channel activity is coupled to in vivo anti-vomiting and anti-nausea effect. In the present study, we further investigated that the inhibitory effect of ginsenosides, active ingredient of Panax ginseng, on 5-HT3A receptor channel activity is also coupled to attenuation of irritable bowel syndrome (IBS), which is induced by colorectal distention (CRD) and $0.6\%$ acetic acid treatment. The CRD-induced visceral pains induced by CRD and acetic acid treatment are measured by frequency of contractions of the external oblique muscle in conscious rats. Treatment of GTS significantly inhibited CRD-induced visceral pain with dose-dependent manner. The $EC_{50}$ was $5.5{\pm}4.7$ mg/kg ($95\%$ confidence intervals: 1.2-15.7) and the antinociceptive effect of GTS on visceral pain was persistent for 4 h. We also compared the effects of protopanaxadiol (PD) ginsenosides and protopanaxatriol (PT) ginsenosides with saline on acetic acid-and CRD-induced visceral pain, and found that protopanaxatriol (PT) ginsenosides was much more potent than PD ginsenosides in attenuating CRD-induced visceral pain. These results indicate that U ginsenosides of Panax ginseng are components far attenuation of experimentally CRD-induced visceral pains.