• Title, Summary, Keyword: Nociception

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Antinociceptive Effects of Intrathecal Metabotropic Glutamate Receptor Compounds and Morphine in Rats

  • Choi, Jeong II;Lee, Hyung Kon;Chung, Sung Tae;Kim, Chang Mo;Bae, Hong Beom;Kim, Seok Jai;Yoon, Myung Ha;Chung, Sung Su;Jeong, Chang Young
    • The Korean Journal of Pain
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    • v.18 no.1
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    • pp.1-9
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    • 2005
  • Background: Spinal metabotropic glutamate receptors (mGluRs) and opioid receptors are involved in the modulation of nociception. Although opioid receptors agonists are active for pain, the effects of the compounds for the mGluRs have not been definitely investigated at the spinal level. We examined the effects of the intrathecal mGluR compounds and morphine in the nociceptive test, and then we further clarified the role of the spinal mGluRs. In addition, the nature of the pharmacological interaction after the coadministration of mGluRs compounds with morphine was determined. Methods: Catheters were inserted into the intrathecal space of male SD rats. For the induction of pain, $50{\mu}l$ of 5% formalin solution or a thermal stimulus was applied to the hindpaw. An isobolographic analysis was used for the evaluation of the drug interaction. Results: Neither group I mGluR compounds nor group III mGluR compounds produced any antinociceptive effect in the formalin test. The group II mGluR agonist (APDC) had little effect on the formalin-induced nociception. The group II mGluR antagonist (LY 341495) caused a dose-dependent suppression of the phase 2 flinching response on the formalin test, but it did not reduce the phase 1 response of the formalin test nor did it increase the withdrawal latency of the thermal stimulus. Isobolographic analysis revealed a synergistic interaction after the intrathecal delivery of a LY 341495-morphine mixture. Conclusions: These results suggest that group II mGluRs are involved in the facilitated processing at the spinal level, and the combination of LY 341495 with morphine may be useful to manage the facilitated pain state.

The Role of the ATP in the Pain Signal Transmission (통증 신호 전달에 있어서 ATP의 역할)

  • Koo Hyun-Mo;Nam Ki-Won;Kim Jin-sang
    • The Journal of Korean Physical Therapy
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    • v.14 no.4
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    • pp.20-27
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    • 2002
  • A role for ATP in nociception and pain induction was proposed. ATP-gated P2X ion channel receptors are localized throughout the nervous system and have been identified on neurons which participate in conduction of nociceptive information from the periphery to central nervous system. We consider the role of ATP as a peripheral activator of nociceptive sensory neuron via ATP-gated ion channels.

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Brain Uptake and the Analgesic Effect of Oxytocin - its Usefulness as an Analgesic Agent

  • Kang, Young-Sook;Park, Ji-Hyun
    • Archives of Pharmacal Research
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    • v.23 no.4
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    • pp.391-395
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    • 2000
  • To establish the usefulness of oxytocin (OT) as an analgesic for women in delivery, the pharmacokinetic parameters and blood-brain barrier (BBB) permeability of [$^3H$] OT were obtained using an intravenous injection technique or the internal carotid artery perfusion/capillary depletion (ICAP/CDM) method. Brain uptake of OT was similar to that of sucrose, plasma space marker, indicating that OT has a poor BBB permeability. Moreover, the analgesic effects of OT injected through the jugular vein on nociception were evaluated by the tail-flick method. The antinociceptive effects of OT injected at a dose of 0.2 ${m}g/kg$or 2 ${m}g/kg$ were dose-dependent. In addition, the analgesic effects of OT on the CNS were unaffected by naloxone, a m-receptor antagonist. In a similar manner to the opioid system, OT may play a modulatory role in antinociception.

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Combination of a Rapidly Penetrating Agonist and a Slowly Penetrating Antagonist Affords Agonist Action of Limited Duration at the Cellular Level

  • Pearce, Larry V.;Ann, Jihyae;Blumberg, Peter M.;Lee, Jeewoo
    • Biomolecules & Therapeutics
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    • v.27 no.5
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    • pp.435-441
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    • 2019
  • The capsaicin receptor TRPV1 (transient receptor potential vanilloid 1) has been an object of intense interest for pharmacological development on account of its critical role in nociception. In the course of structure activity analysis, it has become apparent that TRPV1 ligands may vary dramatically in the rates at which they interact with TRPV1, presumably reflecting differences in their abilities to penetrate into the cell. Using a fast penetrating agonist together with an excess of a slower penetrating antagonist, we find that we can induce an agonist response of limited duration and, moreover, the duration of the agonist response remains largely independent of the absolute dose of agonist, as long as the ratio of antagonist to agonist is held constant. This general approach for limiting agonist duration under conditions in which absolute agonist dose is variable should have more general applicability.

Phosphorylation by $Ca^{+2}$/calmodulin-dependent Kinase II Regulates Binding of Capsaicin to VR1

  • Koo, Jae-Yeon;Kim, Sang-Sung;Kim, Man-Soo;Park, Seung-Pyo;Shim, Won-Sik;Yang, Young-Duk;Cho, Hwa-Won;Kim, Mi-Sook;Kim, Byung-Moon;Oh, Uh-Taek
    • Proceedings of the PSK Conference
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    • pp.128.1-128
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    • 2003
  • VR1, a capsaicin receptor, is now known to playa major role in mediating inflammatory thermal nociception. Although the physiological role or biophysical properties of VR1 are known, its activation mechanisms by ligands are poorly understood. Here, we show that VR1 requires phosphorylation by $Ca^{2+}$-calmodulin-dependent kinase II (CaMKII) for its activation by capsaicin. In contrast, dephosphorylation by calcineurin, leads to desensitization of the receptor. Point mutation of VR1 at two putative consensus sites for CaMKII fails to elicit capsaicin-sensitive currents with concomitant reduction in phosphorylation of VR1 in vivo. (omitted)

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Synthesis and Two Electrode Voltage Clamp Assay of PPADS Derivatives as the P2X Antagonists

  • Lee, Jung-Sun;Moon, Hyun-Duck;Park, Chul-Seung;Kim, Yong-Chul
    • Proceedings of the PSK Conference
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    • pp.178.3-178
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    • 2003
  • P2X receptors are ligand gated cation channels activated by the binding of extracellular adenosine 5'-triphosphate (ATP) and classified into 7 subtype families. $P2X_1$ receptors are abundantly expressed in smooth muscle mediates blood vessel and mediate constriction upon binding of neuronal ATP. The activation of $P2X_3$ receptor by ATP has been known to initiate the pain signaling in the peripheral nervous system, which is involved in chronic inflammatory nociception and neuropathic pain by nerve injury. (omitted)

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Chain-branched Acyclic Phenethylthiocarbamates as Vanilloid Receptor Antagonists

  • Kim, Hee-Doo;Yoon, Jung-Wha;Choi, Hye-Young;Lee, Hyun-Joo;Ryu, Chong-Hyun;Park, Young-Ho;Suh, Young-Ger;Oh, Uh-Taek;Park, Hyeung-Guen
    • Proceedings of the PSK Conference
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    • pp.241.3-242
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    • 2003
  • By acting on vanilloid receptor(VR1). capsaicin excites and then desensitizes a subset of primary neurons involved in nociception, neurogenic inflammation, and a variety of local regulatory functions. Due to this unique biological activity, VR1 is at present one of the most attractive targets for the treatment of pain. However, despite the concentrated effort on agonists, they have been exposed to the side effects such as pungency and/or hypothermia responses. (omitted)

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The Mechanism of Thermoregulatory Action of Capsaicin Is Different from That of Its Antinociceptive Effect in Guinea Pig

  • Yi-Sook JUNG;Tai-Soon CHO;Shin, Hwa-Sup
    • 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.

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Alpha-Calcitonin Gene-Related Peptide-Null Mice Shows Normal Responses to Various Noxious Stimuli

  • Lee, Jong-Ho;Emeson Ronald B.
    • The Korean Journal of Physiology and Pharmacology
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    • v.10 no.6
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    • pp.323-327
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    • 2006
  • Despite the wealth of data concerning the roles of ${\alpha}-CGRP$ in nociceptive behaviors, ${\alpha}-CGRP-null$ mice showed no obvious phenotypic differences in nociceptive behaviors from wild type. The present studies specifically demonstrate that ${\alpha}-CGRP$ null mice showed no CGRP immunoreactivity from the spinal cord, implying that CGRPs in the mice spinal cord are mainly a-isoforms. However, the nociceptive behaviors of the null mice are not significantly different from the wild type mice in thermal nociceptive behaviors on hotplate, chemical nociception tests to intraplantar capsaicin or formalin injection, and visceral pain behaviors to intraperitoneal acetic acid or magnesium sulfate injections. These data suggest that ${\alpha}-CGRP$ is dispensable for nociceptive behaviors or that compensatory mechanisms may exist to overcome the absence of this peptide.

Effects of Achyrantes japonica on Carrageenan-Induced Arthritis Rat Model (Carrageenan으로 유발한 관절염 쥐에서의 우슬추출물 효과)

  • Kim, Young-Ock;Lee, San-Won;Lee, Seung-Eun
    • Korean Journal of Medicinal Crop Science
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    • v.17 no.6
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    • pp.470-474
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    • 2009
  • Achyrantes japonica (AJ) has been used to treat edema and arthritis in the traditional Korean medicine. To elucidate the anti-inflammatory and anti-nociceptive effects of ethanol extract of AJ, the carrageenan-induced paw edema using a plethysmometer and thermal hypersensitivity using the plantar test were measured. Ibuprofen was used as a control drug. Treatment with AJ (200mg/kg p.o.) significantly reduced paw edema, compared to the carrageenan - treated rats. In the plantar test, the thermal withdrawal latency in AJ - treated group was significantly increased than the carrageenan - treated group. The results indicate that AJ could have be the anti-inflammatory and anti-nociceptive properties.