• Title, Summary, Keyword: Nociception

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Acute Phase Protein Lipocalin-2 Is Associated with Formalin-induced Nociception and Pathological Pain

  • Jha, Mithilesh Kumar;Jeon, Sangmin;Jin, Myungwon;Lee, Won-Ha;Suk, Kyoungho
    • IMMUNE NETWORK
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    • v.13 no.6
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    • pp.289-294
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    • 2013
  • Lipocalin-2 (LCN2) is an acute-phase protein induced by injury, infection, or other inflammatory stimuli. LCN2 binds small hydrophobic ligands and interacts with cell surface receptor to regulate diverse cellular processes. The role of LCN2 as a chemokine inducer in the central nervous system (CNS) has been previously reported. Based on the previous participation of LCN2 in neuroinflammation, we investigated the role of LCN2 in formalin-induced nociception and pathological pain. Formalin-induced nociceptive behaviors (licking/biting) and spinal microglial activation were significantly reduced in the second or late phase of the formalin test in Lcn2 knockout mice. Likewise, antibody-mediated neutralization of spinal LCN2 attenuated the mechanical hypersensitivity induced by peripheral nerve injury in mice. Taken together, our results suggest that LCN2 can be therapeutically targeted, presumably for both prevention and reversal of acute inflammatory pain as well as pathological pain.

Anti-nociceptive activity of Corylopsis gotoana (히어리의 진통(鎭痛) 효능(效能))

  • Park, Zi Won;An, Soon Young;Yun, Sun Hwa;Shin, Youn Chel;Yang, Woo In;Lee, Se Youn;Cha, Dong Seok;Jeon, Hoon
    • Korean Journal of Pharmacognosy
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    • v.50 no.4
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    • pp.272-276
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    • 2019
  • Corylopsis gotoana has been widely used as a traditional medicine for the treatment of lots of disease including cold, edema and vomiting. However pharmacological and phytochemical studies on the C. gotoana are extremely limited. Here in this study, the author investigated the anti-nociceptive effects of the methanolic extract of Corylopsis gotoana (MCG) using various pain models. In the present study, MCG exhibited strong and dose-dependent anti-nociceptive activities on various experimental pain models including thermal nociception and chemical nociception, compared to positive control such as tramadol and indomethacin. In addition, the result from combination test using naloxone, analgesic activity of MCG was slightly reduced, indicating that MCG acts as a partial opioid receptor agonist. These results demonstrated that MCG has potent analgesic potential and thus it may be possibly used as a valuable anti-nociceptive agent.

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Introduction of Visceral Pain Model to Test of Visceral Nociception in the Rats (백서의 내장 신경통 연구를 위한 Visceral Pain Model(VPM)의 소개)

  • Lee, Chul-Woo
    • The Korean Journal of Pain
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    • v.8 no.1
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    • pp.25-30
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    • 1995
  • Anlgesic agents against visceral pain typically rely on a noxious chemical irritation of the peritoneum, e. g., acetic acid and phenylquinone writhing test. While useful, this type of assay depends upon an acute inflammation and the release of local alogens. Further, ethical and scientific constraints prevent repeated assessments in a single animal, thereby compounding the difficulty of assessing tolerance development to analgesic agents. To overcome these constraints, Colburn et al. developed a model for mechanical visceral pain model (VPM) based on a repeatable and reversible duodenal distention in the rat. A chronic indwelling intraduodenal balloon catheter is well tolerated and upon inflation produces a writhing response graded in proportion to distention. This response is inhibited by morphine in a dose dependent manner. We found that a model for visceral pain was thought to be a great value.

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Antinociceptive Effects of an Ethyl Acetate Soluble Fraction of Spirodela polyrrhiza

  • Ko, Sung-Hoon;Kim, Jin-Kyu;Kim, Jong-Soo;Lee, Jae-Hyuk;Park, Sang-Youel;Jeon, Hoon
    • Natural Product Sciences
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    • v.17 no.4
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    • pp.303-308
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    • 2011
  • Spirodela polyrrhiza L. Schleid. (Lemnaceae), also known as 'duckweed', is a traditional medicine in Korea. The whole plant is used to treat many diseases, including the common cold, edema, acute nephritis, and urticaria. The present study investigated antinociceptive properties of the EtOAc soluble fraction of S. polyrrhiza (ESP). The antinociceptive activities of ESP were studied using experimental models of pain, including thermal nociception methods, such as the tail immersion test and the hotplate test. Moreover, we studied chemical nociception induced by intraperitoneal acetic acid and subplantar formalin in mice. ESP exhibited dose-dependent antinociceptive activity in both thermal and chemical pain models. In a drug combination test using the opioid receptor antagonist naloxone, diminished analgesic activities of ESP were observed, indicating that the antinociceptive activity of ESP is mediated by opioid receptors.

Sedative and Antinociceptive Properties of Lindera obtusiloba

  • Lee, Yong Jae;Lee, Dong Keon;Kim, Jong Soo;Park, Kyoung Jae;Cha, Dong Seok;Kim, Dae Keun;Kwon, Jin;Oh, Chan Ho;Kim, Kang San;Jeon, Hoon
    • Natural Product Sciences
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    • v.18 no.4
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    • pp.215-220
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    • 2012
  • The stem of Lindera obtusiloba (Lauraceae), has been widely used as a traditional medicine for the treatment of abdominal pain, bruise and hepatocirrhosis. In the present study, antinociceptive and sedative properties of the methanol extract of L. obtusiloba (MLO) were evaluated. MLO demonstrated strong and dose-dependent antinociceptive activities on various experimental pain models including thermal nociception and chemical nociception, compared to tramadol and indomethacin, reference drugs. In combination test using naloxone, the diminished analgesic activity of MLO was observed, indicating the relation with opioid receptor. Moreover, MLO also decreases pentobarbital-induced sleep latency and increases sleeping time suggesting its hypnotic and sedative action. The present results indicate that MLO could be used as valuable antinociceptive and sedative agent for the treatment of various diseases.

Anti-nociceptive and Anti-inflammatory Properties of Ilex latifolia and its Active Component, 3,5-Di-caffeoyl Quinic Acid Methyl Ester

  • Kim, Joo Youn;Lee, Hong Kyu;Seong, Yeon Hee
    • Natural Product Sciences
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    • v.25 no.1
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    • pp.64-71
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    • 2019
  • The present study was conducted to investigate anti-nociceptive and anti-inflammatory effects of the leaves of Ilex latifolia Thunb (I. latifolia) in in vivo and in vitro. Writhing responses induced by acetic acid and formalin- and thermal stimuli (tail flick and hot plate tests)-induced pain responses for nociception were evaluated in mice. I. latifolia (50 - 200 mg/kg, p.o.) and ibuprofen (100 mg/kg, p.o.), a positive non-steroidal anti-inflammatory drug (NSAID), inhibited the acetic acid-induced writhing response and the second phase response (peripheral inflammatory response) in the formalin test, but did not protect against thermal nociception and the first phase response (central response) in the formalin test. These results show that I. latifolia has a significant anti-nociceptive effect that appears to be peripheral, but not central. Additionally, I. latifolia (50 and $100{\mu}g/mL$) and 3,5-di-caffeoyl quinic acid methyl ester ($5{\mu}M$) isolated from I. latifolia as an active compound significantly inhibited LPS-induced NO production and mRNA expression of the pro-inflammatory mediators, iNOS and COX-2, and the pro-inflammatory cytokines, IL-6 and $IL-1{\beta}$, in RAW 264.7 macrophages. These results suggest that I. latifolia can produce antinociceptive effects peripherally, but not centrally, via anti-inflammatory activity and supports a possible use of I. latifolia to treat pain and inflammation.

Anti-nociceptive and Anti-inflammatory Effect of an Ethanol Extract Mixture of Vitis amurensis, Aralia cordata, and Glycyrrhizae radix

  • Park, Sang-Hwa;Seong, Yeon Hee
    • Journal of Biomedical and Translational Research
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    • v.18 no.2
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    • pp.60-66
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    • 2017
  • Vitis amurensis, Aralia cordata, and Glycyrrhizae radix have been widely used in Korea, China, and Japan because of their anti-oxidative and anti-inflammatory activities. The present study investigated the anti-nociceptive and anti-inflammatory properties of an ethanol extract (SSB) of a mixture of three medicinal plants of Vitis amurensis (stem and leaf), Aralia cordata (stem and leaf), and Glycyrrhizae radix. Anti-nociceptive activity was determined using chemical (acetic acid and formalin) and thermal (hot plate) stimuli-induced algesia tests. Formalin-induced paw edema was evaluated for anti-inflammatory activity. SSB (25-100 mg/kg, p.o.) and ibuprofen (100 mg/kg, p.o.), a positive non-steroidal anti-inflammatory drug (NSAID), significantly inhibited the acetic acid-induced writhing response caused by peripherally mediated algesia, but failed to protect thermal nociception in the hot plate test that was employed for centrally mediated analgesic activity. However, morphine (5 mg/kg, s.c.) used as a positive opioid control alleviated the acetic acid-induced writhing response and thermal nociception in the hot plate test. In the formalin test, SSB (50 and 100 mg/kg, p.o.) inhibited the second phase response (peripheral inflammatory algesia), but not the first phase response (central algesia), whereas morphine inhibited both phases of the pain response. Both SSB (25-100 mg/kg, p.o.) and ibuprofen (200 mg/kg) caused significant reduction of the formalin-induced increase of paw thickness, which was the index of inflammation. These results suggest that SSB has a significant anti-nociceptive activity that seems to be peripheral, but not central. SSB also displays anti-inflammatory activity in an acute inflammatory model. The present study supports a possible use of SSB to treat pain and inflammation.

Analgesic Effect of Electroacupuncture on the Pain Induced by Electrical Stimulation (전기자극에 의해 유발된 통증에 대한 말초 전침자극의 진통효과)

  • Hwang, Joon-Ha
    • The Korean journal of physiology & pharmacology
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    • v.21 no.1
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    • pp.79-90
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    • 1987
  • The present experiment was performed in 35 normal male volunteers to evaluate the effect of electroacupuncture on the human nociception more clearly and to demonstrate the effect of different parameters of electrical stimulation through acupuncture needles. The threshold of the pain(Tp) and the nociceptive flexion reflex(Tr), the threshold for intolerable pain(Tip) and that for obtaining maximal reflex response(Tmr) were studied before and after electroacupuncture performed on the acupoints of tsusanli and hsuanchung. 1) For the pricking pain, electroacupuncture with intermittent stimulation induced a significant decrease in Tp which recovered after removal of the needles. There was no significant change in other thresholds. 2) For the dull pain, electroacupuncture with intermittent stimulation produced a significant increase in Tp which continued after removal of the needles. But there was no signifcant change in Tip. Electroacupuncture with continuous stimulation induced a slight increase in Tp. 3) After resting without electroacupuncture, Tp and Tip of the dull pain were slightly decreased. These results suggest that electroacupuncture had no significant analgesic effect on the pricking pain induced by electrical stimulation of the foot skin. However, electroacupuncture with intermittent stimulation had significant analgesic effect on the weak dull pain and it had slightly greater analgesic effect than electroacupuncture with continuous stimulation.

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Calcium Ions are Involved in Modulation of Melittin-induced Nociception in Rat: II. Effect of Calcium Chelator

  • Shin, Hong-Kee;Lee, Kyung-Hee;Cho, Chul-Hyun
    • The Korean Journal of Physiology and Pharmacology
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    • v.10 no.6
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    • pp.297-302
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    • 2006
  • Melittin, a major component of bee venom, produces a sustained decrease in mechanical threshold, and an increase in spontaneous flinchings and paw thickness, which are characteristics similar to those induced by whole bee venom. Melittin-induced nociception has been known to be modulated by the changes in the activity of excitatory amino acid receptors, voltage-dependent calcium channels, cyclooxygenase and serotonin receptors. The present study was undertaken to investigate the role of calcium chelators (TMB-8 & Quin 2) in melittin-induced nociceptive responses. Changes of mechanical threshold and spontaneous flinching behaviors were measured at a given time point following intraplantar injection of melittin ($30{\mu}g/paw$). Intrathecal or intraplantar pre-administration and intrathecal posttreatment of TMB-8 and Quin 2 significantly prevented the melittin-induced reduction of mechanical threshold, and intraplantar or intrathecal pre-treatment of TMB-8 and Quin 2 suppressed melittininduced flinching behaviors. These results indicate that calcium ion in the spinal dorsal horn neurons and peripheral nerves plays an important role in the production and maintenance of mechanical allodynia and spontaneous pain by melittin.

Anti-nociceptive Effect of Bee Venom on Capsaicin or Bradykinin-induced Pain (Capsaicin이나 Bradykinin으로 유발된 통증에 대한 봉독의 억제 효과)

  • Yang, Chang-Yeol;Song, Ho-Sueb
    • Journal of Acupuncture Research
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    • v.24 no.2
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    • pp.39-49
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    • 2007
  • 목적 : 봉독으로 유발된 통각수용의 강도와 봉독으로 나타나는 항통각수용(통각억제성)의 강도를 쥐의 포르말린 테스트를 통해 상호관련됨을 확인하고 capsaicin과 bradykinin으로 통증 유발된 쥐의 자발적인 통증행동(핥기횟수측정; LN), 꼬리경타시험(TFL)과 열판시험(HPL)을 통해 봉독의 항통각수용(통각억제)작용을 재확인 하고자 하였다. 방법 : 쥐의 뒷다리에 통증유도 물질인 Capsaicin 또는 Bradykinin을 20${\mu}l$를 주사하여 동통을 유발하고 자발적 통증행동인 핥기횟수측정(LN), 꼬리경타기간(TFL)과 열판 위에서의 온도자극에 쥐가 반응하는 시간을 측정(HPL)하는 실험을 봉독을 주입하거나, 몰핀을 주입하거나, 아무것도 주입하지 않고 통증유발만 시킨 이후에 각각 시행하였다. 결과: 1. Capsaicin 또는 Bradykinin으로 동통유발 후 LN은 두드러증가를 보임, HPL은 감소를 TFL은 두드러진 감소를 나타내었다. 2. 봉독이나 몰핀 주입 30분 후에 Capsaicin으로 동통유발 이후 LN은 봉독과 몰핀에서 모두 현격한 감소를, HPL은 봉침은 현격한 증가를, 몰핀에서는 감소를, TFL은 봉침과 몰핀에서 모두 현격한 증가를 나타내었다. 3 봉독과 몰핀주입 30분후에 Bradykinin으로 동통유발 이후 LN은 봉독은 증가 몰핀은 현격한 감소를, HPL은 봉침은 증가 몰핀에서는 현격한 증가를, TFL은 봉침과 볼핀에서 모두 증가를 나타내었다. 결론 : 봉독은 Capsaicin 또는 Bradykinin으로 동통유발된 통각수용행동을 감소시키는 결과를 나타내었는데 이것은 기존의 연구결과들에서의 봉독의 항통각수용(통각억제성)의 효과를 입증하였고 봉약침은 염증의 개선이나 암과 관련된 동통에 유효한 방법임을 시사하는 것이다.

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