• Title/Summary/Keyword: antinociceptive

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The analgesic effect of Auto-Manual Acupuncture with Twirling Method (자동 염전침의 진통효과)

  • Kim, Kye-jin;Lee, Hyung-suk;Kim, Sun-kwang;Min, Byung-il;Lee, Jae-dong;Park, Dong-suk;Lee, Soon-girl;Kim, Hyung-min
    • Journal of Acupuncture Research
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    • v.21 no.3
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    • pp.133-144
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    • 2004
  • Background and Objective : Twirling is one of the needling methods, which is frequently used for acupuncture in oriental medicine. Some thesis about needle manipulation has been reported that needle manipulation is more effective than plain acupuncture. So we have developed the auto-controlled twirling needle(ACTN) system which is most simple style of needle manipulation. The present study was conducted to see if ACTN can enhance the antinociceptive effect of acupuncture. Methods : To investigate the analgesic effect of acupuncture we used two pain model. One is acute pain model using tail flick latency(TFL), the other is neuropathic pain model using mechanical allodynia. For TFL test, rats were lightly anesthetized with pentobarbital sodium(40 mg/kg, i.p). To produce mechanical allodynia in the rat tail, the right superior caudal trunk was resected between the S1 and S2 spinal nerves. For plain acupuncture(PA), a needle was inserted into a Zusanli(ST36) for 15min. In combining ACTN with PA, twirling needle was performed once in a second. We measured the difference of analgesic effect of only PA and ACTN on two different kinds of pain. Results and conclusion : ACTN increased TFL more than PA. (15min P<0.001, 25min P<0.01). And ACTN also reduced neuropathic pain (15min P<0.01, 25min<0.05). But PA alone can't reduce the neuropathic pain. These results indicate that ACRN had more analgesic effect than PA. The mechanism that play a key role, and the condition which produce best analgesic effect of ACTN are to be studied further.

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Ursodeoxycholic Acid Ameliorates Pain Severity and Cartilage Degeneration in Monosodium Iodoacetate-Induced Osteoarthritis in Rats

  • Moon, Su-Jin;Jeong, Jeong-Hee;Jhun, Joo Yeon;Yang, Eun Ji;Min, Jun-Ki;Choi, Jong Young;Cho, Mi-La
    • IMMUNE NETWORK
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    • v.14 no.1
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    • pp.45-53
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    • 2014
  • Osteoarthritis (OA) is a degenerative joint disease characterized by a progressive loss of cartilage. And, increased oxidative stress plays a relevant role in the pathogenesis of OA. Ursodeoxycholic acid (UDCA) is a used drug for liver diseases known for its free radical-scavenging property. The objectives of this study were to investigate the in vivo effects of UDCA on pain severity and cartilage degeneration using an experimental OA model and to explore its mode of actions. OA was induced in rats by intra-articular injection of monosodium iodoacetate (MIA) to the knee. Oral administration UDCA was initiated on the day of MIA injection. Limb nociception was assessed by measuring the paw withdrawal latency and threshold. Samples were analyzed macroscopically and histologically. Immunohistochemistry was used to investigate the expression of interleukin-$1{\beta}$ (IL-$1{\beta}$), IL-6, nitrotyrosine and inducible nitric oxide synthase (iNOS) in knee joints. UDCA showed an antinociceptive property and attenuated cartilage degeneration. OA rats given oral UDCA significantly exhibited a decreased number of osteoclasts in subchondral bone legion compared with the vehicle-treated OA group. UDCA reduced the expression of IL-$1{\beta}$, IL-6, nitrotyrosine and iNOS in articular cartilage. UDCA treatment significantly attenuated the mRNA expression of matrix metalloproteinase-3 (MMP-3), -13, and ADAMTS5 in IL-$1{\beta}$-stimulated human OA chondrocytes. These results show the inhibitory effects of UDCA on pain production and cartilage degeneration in experimentally induced OA. The chondroprotective properties of UDCA were achieved by suppressing oxidative damage and inhibiting catabolic factors that are implicated in the pathogenesis of cartilage damage in OA.

The Analgesic Effect and the Mechanism of Electroacupuncture on Thermal Hyperalgesia in the Rat Model of Collagenase-induced Arthritis: Mediation by Adrenergic Receptors (Collagenase-induced Arthritis Rat Model에서 Thermal Hyperalgesia에 대한 전침(電鍼)의 진통효과(鎭痛效果) 및 기전연구: Adrenergic Mechanism에 대(對)한 연구(硏究))

  • Seo, Byung-Kwan;Park, Dong-Suk;Baek, Yong-Hyeon
    • Journal of Acupuncture Research
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    • v.28 no.2
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    • pp.57-67
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    • 2011
  • 목적 : Collagenase-induced osteoarthritis(OA) 동물 모델에서 전침의 adrenergic mechanism을 연구하고자 한다. 방법 : Collagenase-induced arthritis(CIA)를 유발하기 위하여 5주령의 male Sprague-Dawley rat의 뒷다리 좌측 무릎 관절에 0.05ml의 4mg/ml collagenase solution을 intra-articular 주입하고, 다시 4일 후에 같은 부위에 같은 농도의 collagenase solution을 intra-articular boosting injection 시행한 뒤, gross, histopathological features 및 biomarker activity 변화를 관찰하였다. 예비실험을 통하여 CIA rat model에서 진통효과를 발휘하는 것으로 확인한, 족삼리(足三里) ($ST_{36}$)에 대한 저빈도 train pulse EA stimulation (2Hz, 0.07 mA, 0.3ms)을 침치료 방법으로 적용하였다. 전침의 진통기전을 확인하기 위하여, ${\alpha}1$-adrenergic antagonist (prazosin, 1 mg/kg, i.p.), ${\alpha}2$-adrenergic receptor antagonist (yohimbine, 2mg/kg, i.p.), ${\alpha}1$-adrenergic receptor agonist(phenylephrine, 2mg/kg, i.p.), ${\alpha}2$-adrenergic receptor agonist(clonidine, $40{\mu}g$/kg, i.p.)을 전침시행 20분 전에 복강 내로 전처치하였다. Tail flick unit(Ugo Basile Model 7360)을 이용하여 열자극에 대한 통증역치를 측정하였다. 결과 : 퇴행성관절염 징후(gross, histopathological features)와 통증역치의 변화가 최대값을 나타내는 CIA 유발 4주차에 저빈도 전침자극(train pulse, 2Hz, 0.07mA, 0.3ms)을 족삼리($ST_{36}$)에 적용하였으며, 족삼리 전침의 진통효과는 ${\alpha}2$-adrenergic receptor antagonist(yohimbine, 2mg/kg, i.p.)전처치에 의해 억제되었으나, ${\alpha}1$-adrenergic antagonist(prazosin, 1 mg/kg, i.p.)전처치에는 억제되지 않았다. 또 ${\alpha}2$-adrenergic receptor agonist(clonidine, $40{\mu}g$/kg, i.p.)의 전처치를 통하여 유의한 synergistic analgesic effect가 관찰되었으나, ${\alpha}1$-adrenergic receptor agonist(phenylephrine, 2mg/kg, i.p.)의 전처치는 전침의 진통효과에 synergistic effect를 미치지 않는 것으로 나타났다. 결론 : 저빈도 족삼리 전침은 CIA로 유발된 염증성 통증에 대하여 진통효과를 발휘하며, 이는 ${\alpha}2$-adrenergic receptor에 의하여 매개되는 것으로 보이며 ${\alpha}1$-adrenergic receptor는 영향을 미치지 않는 것으로 사료된다.

Pain-reducing Effect by Transplants of Isolated Xenogeneic Chromaffin Cells in Mouse (추출된 이종 크롬 친화성 세포의 이식에 의한 마우스에서의 통증 완화 효과)

  • Han, Young-Min;Lee, Jong-Phil;Hwang, Hyung-Sik;Song, Joon-Ho;Park, Sang-Koo;Park, Suk-Ju;Jin, Jae-Kwang;Choi, Eun-Kyoung;Kim, Yong-Sun;Ahn, Myung-Soo
    • Journal of Korean Neurosurgical Society
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    • v.30 no.4
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    • pp.417-424
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    • 2001
  • Objective : Adrenal medullary chromaffin cells are known to release analgesic substances such as opioides and catecholamines. Transplantation of them is a novel method that challenges current approaches in treating chronic pain. The transplantation of xenogeneic chromaffin cells into the central nervous system(CNS) supply antinociception in animals. In this study, we investigated the analgesic effects of rat adrenal medullary chromaffin cells transplanted into the CNS of the mouse. To study the antinociceptive efficacy of transplanted chromaffin cells, the survival of rat adrenal medullary chromaffin cells transplanted into the CNS of mouse was determined. Methods : The adrenal medullary chromaffin cells isolated from rat were transplanted into the striatum of mouse. These cells were confirmed of the release of Met-enkephalin and Leu-enkephalin by HPLC, and immunoblots for tyrosine hydroxylase(TH). Two weeks after transplantation, we performed immunohistochemistry for TH to determine the survival of implanted cells and assessed pain sensitivity at the same time. Results : The isolated rat adrenal medullary chromaffin cells were positive for anti-TH antibody and released Met-enkephalin and Leu-enkephalin more than rat endothelial cells. Transplanted rat chromaffin cells were stained with anti-TH antibody in striatum of mouse after 2 weeks. Pain sensitivity was reduced on the chromaffin cell-transplanted mouse compared to endothelial cell-transplanted mouse by the hot plate test. Conclusion : These results suggest that the rat chromaffin cells were suitably transplanted into the CNS of mouse. This approach could be used as a therapy for reducing of chronic pain induced by cancer or neuronal injury.

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The Effect of ATP-sensitive Potassium Channel on R-PIA Induced Mechanical Antiallodynia in a Peripheral Neuropathic Rat (신경병증 통증 모델의 백서에서 R-PIA의 기계적 항이질통 효과와 ATP-감수성 칼륨 통로와의 연관성에 대한 연구)

  • Min, Hong Gi;Seong, Seung Hye;Jung, Sung Mun;Shin, Jin Woo;Gwak, Mi Jung;Leem, Jeong Gill;Lee, Cheong
    • The Korean Journal of Pain
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    • v.18 no.2
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    • pp.107-112
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    • 2005
  • Background: Nerve ligation injury may produce mechanical allodynia, but this can be reversed after an intrathecal administration of adenosine analogues. In many animal and human studies, ATP-sensitive potassium channel blockers have been known to reverse the antinociceptive effect of various drugs. This study was performed to evaluate the mechanical antiallodynic effects of spinal R-PIA (Adenosine A1 receptor agonist) and the reversal of these effects due to pretreatment with glibenclamide (ATP-sensitive potassium channel blocker). Thus, the relationship between the antiallodynic effects of R-PIA and ATP-sensitive potassium channel were investigated in a neuropathic model. Methods: Male Sprague Dawley rats were prepared by tightly ligating the left lumbar 5th and 6th spinal nerves and implantation of a chronic lumbar intrathecal catheter for drug administration. The mechanical allodynia was measured by applying von Frey filaments ipsilateral to the lesioned hind paw. And the thresholds for paw withdrawal assessed. In study 1, either R-PIA (0.5, 1 and $2{\mu}g$) or saline were administered intrathecally for the examination of the antiallodynic effect of R-PIA. In study 2, glibenclamide (2, 5, 10 and 20 nM) was administered intrathecally 5 min prior to an R-PIA injection for investigation of the reversal of the antiallodynic effects of R-PIA. Results: The antiallodynic effect of R-PIA was produced in a dose dependent manner. In study 1, the paw withdrawal threshold was significantly increased with $2{\mu}g$ R-PIA (P < 0.05). In study 2, the paw withdrawal threshold with $2{\mu}g$ R-PIA was significantly decreased almost dose dependently by intrathecal pretreatment of 5, 10 and 20 nM glibenclamide (P < 0.05). Conclusions: These results demonstrated that an intrathecal injection of ATP-sensitive potassium channel blockers prior to an intrathecal injection of adenosine A1 receptors agonist had an antagonistic effect on R-PIA induced antiallodynia. The results suggest that the mechanism of mechanical antiallodynia, as induced by an intrathecal injection of R-PIA, may involve the ATP-sensitive potassium channel at both the spinal and supraspinal level in a rat nerve ligation injury model.

The Role of Spinal Dopaminergic Transmission in the Analgesic Effect of Nefopam on Rat Inflammatory Pain

  • Kim, Do Yun;Chae, Joo Wung;Lim, Chang Hun;Heo, Bong Ha;Park, Keun Suk;Lee, Hyung Gon;Choi, Jeong Il;Yoon, Myung Ha;Kim, Woong Mo
    • The Korean Journal of Pain
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    • v.29 no.3
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    • pp.164-171
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    • 2016
  • Background: Nefopam has been known as an inhibitor of the reuptake of monoamines, and the noradrenergic and/or serotonergic system has been focused on as a mechanism of its analgesic action. Here we investigated the role of the spinal dopaminergic neurotransmission in the antinociceptive effect of nefopam administered intravenously or intrathecally. Methods: The effects of intravenously and intrathecally administered nefopam were examined using the rat formalin test. Then we performed a microdialysis study to confirm the change of extracellular dopamine concentration in the spinal dorsal horn by nefopam. To determine whether the changes of dopamine level are associated with the nefopam analgesia, its mechanism was investigated pharmacologically via pretreatment with sulpiride, a dopaminergic D2 receptor antagonist. Results: When nefopam was administered intravenously the flinching responses in phase I of the formalin test were decreased, but not those in phase II of the formalin test were decreased. Intrathecally injected nefopam reduced the flinching responses in both phases of the formalin test in a dose dependent manner. Microdialysis study revealed a significant increase of the level of dopamine in the spinal cord by intrathecally administered nefopam (about 3.8 fold the baseline value) but not by that administered intravenously. The analgesic effects of intrathecally injected nefopam were not affected by pretreatment with sulpiride, and neither were those of the intravenous nefopam. Conclusions: Both the intravenously and intrathecally administered nefopam effectively relieved inflammatory pain in rats. Nefopam may act as an inhibitor of dopamine reuptake when delivered into the spinal cord. However, the analgesic mechanism of nefopam may not involve the dopaminergic transmission at the spinal level.

Participation of Central $P2X_7$ Receptors in CFA-induced Inflammatory Pain in the Orofacial Area of Rats

  • Yang, Kui-Ye;Kim, Myung-Dong;Ju, Jin-Sook;Kim, Min-Ji;Ahn, Dong-Kuk
    • International Journal of Oral Biology
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    • v.39 no.1
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    • pp.49-56
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    • 2014
  • We investigated the role of central P2X receptors in inflammatory pain transmission in the orofacial area in rats. Experiments were carried out using male Sprague-Dawley rats weighing 230-280g. Complete Freund's adjuvant (CFA, $40{\mu}L$) was applied subcutaneously to the vibrissa pad to produce inflammatory pain. The intracisternal administration of iso-PPADS tetrasodium salt, a non-selective P2X receptor antagonist, A317491 sodium salt hydrate, a $P2X_{2/3}$ receptor antagonist, 5-BDBD, a $P2X_4$ receptor antagonist, or A438079 hydrochloride, a $P2X_7$ receptor antagonist, was performed 5 days after CFA injection. Subcutaneous injections of CFA produced increases in thermal hypersensitivity. Intracisternal injections of iso-PPADS ($25{\mu}g$) or A438079 (25 or $50{\mu}g$) produced significant anti-hyperalgesic effects against thermal stimuli compared to the vehicle group. A317491 or 5-BDBD did not affect the head withdrawal latency times in rats showing an inflammatory response. Subcutaneous injections of CFA resulted in the up-regulation of OX-42, a microglia marker, and GFAP, an astrocyte marker, in the medullary dorsal horn. The intracisternal administration of A438079 reduced the numbers of activated microglia and astrocytes in the medullary dorsal horn. These results suggest that a blockade of the central $P2X_7$ receptor produces antinociceptive effects, mediated by inhibition of glial cell function in the medullary dorsal horn. These data also indicate that central $P2X_7$ receptors are potential targets for future therapeutic approaches to inflammatory pain in the orofacial area.

Effects of Ethanol Extract from Lathyrus palustris on Anti-inflammation Response of RAW 264.7 Cell (RAW 264.7 대식세포 염증반응에 대한 털연리초 에탄올 추출물의 항염증 효과)

  • Nam, Jung Hwan
    • Korean Journal of Plant Resources
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    • v.33 no.4
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    • pp.287-292
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    • 2020
  • Lathyrus palustris often used as a treatment for inflammation of the kidneys in Korean traditional medication. Generally, drugs for arthritis have anti-inflammatory and antinociceptive properties. However, the validity of the anti-inflammatory effect has not been scientifically investigated so far. Therefore, the purpose of the research was to investigate the latent anti-inflammatory ability of L. palustris using the ethanol extract. To evaluate the anti-inflammatory activities, we examined the inflammatory arbitrators such as a nitric oxide (NO) and prostaglandin E2 (PGE2) on RAW 264.7 cells. Our results indicated that ethanol extract significantly inhibited the lipopolysaccharide E (LPS) derived PGE2 production in RAW 264.7 cell. The inhibitory activity of ethanol extract for PGE2 tests with inhibition ratio showed in 40 ㎍/mL. Overall, PGE2 tests had a higher inhibitory effect on inflammation than NO tests. This result anticipated that the ethanol extract from L. palustris is a good candidate for developing the origin of anti-inflammatory agents.

Systemically administered neurotensin receptor agonist produces antinociception through activation of spinally projecting serotonergic neurons in the rostral ventromedial medulla

  • Li, Yaqun;Kang, Dong Ho;Kim, Woong Mo;Lee, Hyung Gon;Kim, Seung Hoon;You, Hyun Eung;Choi, Jeong Il;Yoon, Myung Ha
    • The Korean Journal of Pain
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    • v.34 no.1
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    • pp.58-65
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    • 2021
  • Background: Supraspinal delivery of neurotensin (NTS), which may contribute to the effect of a systemically administered agonist, has been reported to be either pronociceptive or antinociceptive. Here, we evaluated the effects of systemically administered NTSR1 agonist in a rat model of neuropathic pain and elucidated the underlying supraspinal mechanism. Methods: Neuropathic pain was induced by L5 and L6 spinal nerve ligation in male Sprague-Dawley rats. The effects of intraperitoneally administered NTSR1 agonist PD 149163 was assessed using von Frey filaments. To examine the role of 5-HT neurotransmission, a serotonin (5-HT) receptor antagonist dihydroergocristine was pretreated intrathecally, and spinal microdialysis studies were performed to measure the change in extracellular level of 5-HT in response to PD 149163 administration. To investigate the supraspinal mechanism, NTSR1 antagonist 48692 was microinjected into the rostral ventromedial medulla (RVM) prior to systemic PD 149163. Additionally, the effect of intrathecal DHE on intra-RVM PD 149163 was assessed. Results: Intraperitoneally administered PD 149163 exhibited a dose-dependent attenuation of mechanical allodynia. This effect was partially reversed by intrathecal pretreatment with dihydroergocristine and was accompanied by an increased extracellular level of 5-HT in the spinal cord. The PD 149163-produced antinociception was also blocked by intra-RVM SB 48692. Direct injection of PD 149163 into the RVM mimicked the maximum effect of the same drug delivered intraperitoneally, which was reversed by intrathecal dihydroergocristine. Conclusions: These observations indicate that systemically administered NTSR1 agonist produces antinociception through the NTSR1 in the RVM, activating descending serotonergic projection to release 5-HT into the spinal dorsal horn.

In vitro anti-inflammatory activity of extracts from Potentilla supina in murine macrophage RAW 264.7 cells (개소시랑개비 추출물의 RAW264.7대식세포에서 in vitro 항염효과)

  • Nam, Jung-Hwan;Kim, Hyun-Sam;Kim, Byoumg-Jin;Yu, Hong-Seob;Chang, Dong-Chil;Jin, Yong-Ik;Yoo, Dong-Lim;Choi, Jong-Keun;Park, Hee-Jhun;Lee, Seung-Bin;Lee, Kyung-Tea;Park, Soo-Jin
    • Journal of Plant Biotechnology
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    • v.44 no.1
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    • pp.76-81
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    • 2017
  • Potentilla supina (Rosaceae) has traditionally been used to treat disorders of hemostasis, dysentery, malaria, bloody discharge and arthritis, and it has antinociceptive and anti-inflammatory properties. However, validity of the anti-inflammatory activity has not been scientifically investigated so far. Therefore, the aim of this study was to investigate the anti-inflammatory potential of P. supina using the ethanolic extract of P. supina and its sub-fractions. To evaluate the anti-inflammatory effects of P. supina, we examined the inflammatory mediators such as nitric oxide (NO), inducible nitric oxide synthase (iNOS) and prostaglandin $E_2$ ($PGE_2$) in RAW 264.7 cells. Our results indicated that ethyl acetate fraction significantly inhibited LPS-induced NO, iNOS and $PGE_2$ production in RAW 264.7 cells. This result showed that ethyl acetate fraction of P. supina is expected to be a good candidate for development into a source of anti-inflammatory agents.