• Title/Summary/Keyword: Antinociceptive effect

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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-inflammatory Activity of Complex Saponin Separated from Pueraria flos and Adzuki Beans Mixture Extract

  • Jung Hwan Nam;Jong Nam Lee;Su hyoung Park;Su Jeong Kim;Hwang Bae Sohn;Do Yeon Kim
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2022.09a
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    • pp.90-90
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    • 2022
  • Pueraria flos and Adzuki Beans contains several bioactive compounds, such as saponin, oleanolic acid, and flavone. Pueraria flos and Adzuki Beans has traditionally been used to treat disorders of antioxidant activity, diabetes and liver detoxication, and it has antinociceptive and anti-inflammatory properties. However, complex saponin were validity of the anti-inflammatory activity has not been scientifically investigated. In this study, to determine anti-inflammatory activity of complex saponin separated from Pueraria flos and Adzuki Beans mixture extract on nitric oxide and prostaglandinE2 assay. The anti-inflammatory activities of complex saponin separated from Pueraria flos and Adzuki Beans mixture extract were evaluated for inhibitory activities against lipopolysacchride induced nitric oxide and prostaglandinE2 production protein expressions in RAW264.7 cell lines. The complex saponin separated from Pueraria flos and Adzuki Beans mixture extract inhibitory activity for both tests with protein high depressions(%) values showed in the ranges of 50~100 ㎍/ml. Overall, prostaglandinE2 tests had a higher inhibitory effect on inflammation than nitricoxide tests. Theseis result suggest a potential role of complex saponin separated from Pueraria flos and Adzuki Beans mixture extract as source of anti-inflammation agent.

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Ferroptosis inhibitor ferrostatin-1 attenuates morphine tolerance development in male rats by inhibiting dorsal root ganglion neuronal ferroptosis

  • Hasan Dirik;Ahmet Sevki Taskiran;Ziad Joha
    • The Korean Journal of Pain
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    • v.37 no.3
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    • pp.233-246
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    • 2024
  • Background: Ferrostatin-1 and liproxstatin-1, both ferroptosis inhibitors, protect cells. Liproxstatin-1 decreases morphine tolerance. Yet, ferrostatin-1's effect on morphine tolerance remains unexplored. This study aimed to evaluate the influence of ferrostatin-1 on the advancement of morphine tolerance and understand the underlying mechanisms in male rats. Methods: This experiment involved 36 adult male Wistar albino rats with an average weight ranging from 220 to 260 g. These rats were categorized into six groups: Control, single dose ferrostatin-1, single dose morphine, single dose ferrostatin-1 + morphine, morphine tolerance (twice daily for five days), and ferrostatin-1 + morphine tolerance (twice daily for five days). The antinociceptive action was evaluated using both the hot plate and tail-flick tests. After completing the analgesic tests, tissue samples were gathered from the dorsal root ganglia (DRG) for subsequent analysis. The levels of glutathione, glutathione peroxidase 4 (GPX4), and nuclear factor erythroid 2-related factor 2 (Nrf2), along with the measurements of total oxidant status (TOS) and total antioxidant status (TAS), were assessed in the tissues of the DRG. Results: After tolerance development, the administration of ferrostatin-1 resulted in a significant decrease in morphine tolerance (P < 0.001). Additionally, ferrostatin-1 treatment led to elevated levels of glutathione, GPX4, Nrf2, and TOS (P < 0.001), while simultaneously causing a decrease in TAS levels (P < 0.001). Conclusions: The study found that ferrostatin-1 can reduce morphine tolerance by suppressing ferroptosis and reducing oxidative stress in DRG neurons, suggesting it as a potential therapy for preventing morphine tolerance.

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.

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.

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.

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.

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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Pain reducing effect of vapocoolant spray during injection and heelstick procedure in neonates (신생아에서 근육 주사 및 발뒤꿈치 천자 시 냉각 분사의 통증감소효과: 냉각 분사와 30% 경구 포도당액의 비교)

  • Choi, Eun Kyong;Jung, Ji Mi;Sin, Jong Beom
    • Clinical and Experimental Pediatrics
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    • v.51 no.5
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    • pp.481-486
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    • 2008
  • Purpose : The aims of this study were to test the efficacy of vapocoolant spray to decrease the symptoms associated with pain in newborns undergoing heel stick and intramuscular injection and compare the pain relief effect of oral glucose. Methods : Randomized, controlled study including sixty newborns undergoing heel stick and intramuscular injection. Group 1 was heelsticked, Group 2 was intramuscular injected, Group A did not recieve any treatment, Group B recieved 30% glucose solution orally, Group C was applied vapocoolant spray symptoms and signs associated with pain at heel stick and intramuscular injection were measured with the premature Infant Pain Profile (PIPP) scale. Results : There was no significant difference in the PIPP score between intramuscular injected group control and heel stick group control (P=0.07). The mean PIPP score of Group 1A (control) $10.6{\pm}2.4$, Group 1B $5.5{\pm}2.0$, Group 1C $5.2{\pm}1.8$. The mean PIPP score 1B and 1C were significantly lower than control (1B P<0.001, 1C P<0.001). The mean PIPP score of Group 2A (control) $12.5{\pm}1.4$, Group 2B $7.0{\pm}1.7$, Group 2C $6.4{\pm}1.6$. The mean PIPP score 2B and 2C were significantly lower than control (2B P<0.001, 2C P<0.001). Conclusion : The antinociceptive effect of vapocoolant sparay is as effective as 30% oral glucose solution for pain control. So this study support the use of vapocoolant spray for reducing pain during painful procedure in the neonatal intensive care units.

Antinociceptive Effect of Testosterone in Androgenized Female Mice (남성화된 암컷 생쥐에서 Testosterone이 통각예민도에 미치는 영향)

  • Chon, Myong-Ho;Kim, Myung-Jung;Park, Je-Min;Yang, Gu-Beum;Lee, Kook-Hee;Jang, Sae-Heon;Kang, Cheol-Joong
    • Korean Journal of Psychosomatic Medicine
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    • v.8 no.1
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    • pp.65-71
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    • 2000
  • Objects : Aimed to test the hypothesis that neonatal testosterone exposure in female mice influences the development of testosterone-related pain inhibitory system and that testosterone administered in adulthood decreases the pain sensitivity. Methods : Thirty androgenized(testosterone propionate $100{\mu}g$ ip within 24 hrs after birth) adult female and twenty five control(normal saline $100{\mu}g$ ip within 24 hrs after birth) adult female mice were injected with testosterone propionate 1mg/kg/day for 3 consecutive days from 84th experimental days. Nociceptive sensitivity was measured before and after treatment of testosterone by tail flick latency on 84th and 86th experimental days. Results : 1) On the 84th experimental day, basal nociceptive sensitivity was significantly higher in the androgenized group($2.7{\pm}0.4$ sec) as compared to the control group($3.3{\pm}1.1$ sec). 2) Testosterone treatment on the 84th experimental day significantly lowered nociceptive sensitivity in both androgenized($5.2{\pm}0.9$ sec) and control groups($4.6{\pm}1.8$ sec). However the effect was significantly greater in the androgenized group. 3) Nociceptive sensitivity on 86th experimental day before administration of testosterone was significantly lower in the androgenized group($4.8{\pm}1.9$ sec) as compared to the control group($3.9{\pm}1.2$ sec). 4) Testosterone treatment on the 86th experimental day significantly lowered the nociceptive sensitivity in both groups, but the androgenized group($5.9{\pm}0.9$ sec) showed significantly lower post-treatment nociceptive sensitivity as compared to the control group($4.9{\pm}1.5$ sec). 5) Nociceptive sensitivity was decreased significantly after injection of testosterone once a day for two consecutive days in the androgenized group(${\Delta}2.1{\pm}1.0$ sec), but not in the control group(${\Delta}0.5{\pm}1.3$ sec). Conclusions : There may be a testosterone-related pain inhibitory system, the development of which is enhanced by exposure to testosterone in the neonatal period, and the activity of which is also mediated by testosterone in the later life.

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