• PNF and Movement
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• v.7 no.3
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• pp.29-38
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• 2009

Purpose : The aim of this study is to examine the effect of the phenol compound-cold therapy plus exercise therapy on the carrageenan(CAR)-induced muscle pain. Method : Mice were injected 0.1ml of 2% CAR into the gastrocmemius(GAS) muscle for the induction of muscle pain. After 4 hours from the injection of CAR, the cold therapy with 1% syringic acid was done to GAS muscle. After 2 hours from cold therapy, the exercise therapy such as muscle stretching, climing- and declining-movements was performed three times interval of 10 minutes in each experimental group. After 4, 10 and 24 hours from CAR-induced muscle pain, the measurements of muscle diameter, paw withdrawal latency(PWL) and, tail flick latency(TFL) were carried out. Results : In this study, the thickness of GAS muscle in CAR-induced muscle pain significantly increased compared with control. While, the thickness of GAS muscle adopted cold syringic acid-therapy with exercise-therapy group was significantly decreased than that of CAR-induced muscle pain. In the measurements of PWL and TFL, cold syringic acid-therapy with exercise-therapy group was remarkably increased than CAR-induced muscle pain group in PWL and TFL. All measurements were showed significantly different between the treated-group and the treated-time. Conclusions : From these results, it is suggested that the cold syringic acid-therapy with exercise-therapy such as muscle stretching, climing- and declining-movement was effective in the prevention of CAR-induced muscle pain by the decrease of muscle thickness and the increase of PWL and TFL.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.3
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• pp.207-216
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• 2021

Several studies have previously reported that exposure to stress provokes behavioral changes, including antinociception, in rodents. In the present study, we studied the effect of acute cold-water (4℃) swimming stress (CWSS) on nociception and the possible changes in several signal molecules in male ICR mice. Here, we show that 3 min of CWSS was sufficient to produce antinociception in tail-flick, hot-plate, von-Frey, writhing, and formalin-induced pain models. Significantly, CWSS strongly reduced nociceptive behavior in the first phase, but not in the second phase, of the formalin-induced pain model. We further examined some signal molecules' expressions in the dorsal root ganglia (DRG) and spinal cord to delineate the possible molecular mechanism involved in the antinociceptive effect under CWSS. CWSS reduced p-ERK, p-AMPKα1, p-AMPKα2, p-Tyk2, and p-STAT3 expression both in the spinal cord and DRG. However, the phosphorylation of mTOR was activated after CWSS in the spinal cord and DRG. Moreover, p-JNK and p-CREB activation were significantly increased by CWSS in the spinal cord, whereas CWSS alleviated JNK and CREB phosphorylation levels in DRG. Our results suggest that the antinociception induced by CWSS may be mediated by several molecules, such as ERK, JNK, CREB, AMPKα1, AMPKα2, mTOR, Tyk2, and STAT3 located in the spinal cord and DRG.

• 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.

• The Korean Journal of Pain
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• v.35 no.1
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• pp.22-32
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• 2022

Background: Migraine headaches have been associated with sensory hyperactivity and anomalies in social/emotional responses. The main objective of this study was to evaluate the potential involvement of orexin 1 receptors (Orx1R) within the basolateral amygdala (BLA) in the modulation of pain and psychosocial dysfunction in a nitroglycerin (NTG)-induced rat model of migraine. Methods: Adult male Wistar rats were injected with NTG (5 mg/kg, intraperitoneal) every second day over nine days to induce migraine. The experiments were done in the following six groups (6 rats per group): untreated control, NTG, NTG plus vehicle, and NTG groups that were post-treated with intra-BLA microinjection of Orx1R antagonist SB-334867 (10, 20, and 40 nM). Thermal hyperalgesia was assessed using the hot plate and tail-flick tests. Moreover, the elevated plus maze (EPM) and open field (OF) tests were used to assess anxiety-like behaviors. The animals' sociability was evaluated using the three-chamber social task. The NTG-induced photophobia was assessed using a light-dark box. Results: We observed no change in NTG-induced thermal hyperalgesia following administration of SB-334867 (10, 20, and 40 nM). However, SB-334867 (20 and 40 nM) aggravated the NTG-induced anxiogenic responses in both the EPM and OF tasks. The NTG-induced social impairment was overpowered by SB-334867 at all doses. Time spent in the dark chamber of light-dark box was significantly increased in rats treated with SB-334867 (20 and 40 nM/rat). Conclusions: The findings suggest a role for Orx1R within the BLA in control comorbid affective complaints with migraine in rats.

• 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.

• 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.

• Journal of Korean Medicine Rehabilitation
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• v.15 no.1
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• pp.127-141
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• 2005

Objectives : This study was performed to investigate the effects of Gamichangbaek-san(Jiaweichangbai-san) on anti-inflammatory, analgesic, anti-febrile and immune response on the arthritis of carrageenan-induced animals. Methods and Materials : Rats were classified into control and sample groups which are 7 individuals each for the experiments about anti-inflammatory and anti-febrile. Each of the 7 mice were classified into normal, control, sample groups for the analgesic experiments. Gamichangbai-san(Jiaweichangbai-san) was administered to sample group and normal saline was administered to normal and control groups. Arthritis was induced by injection of 1% carrageenan $0.1m{\ell}$ and Gamichangbaek-san(Jiaweichangbai-san) was administered after 30 minutes. The change of edema in Carrageenan-induced Arthritic Rats' Paws was measured after 1 hour and 5 hours from the injection of carraqeenan with Plethysmometer(7150, UGO BASILE, ltaly) by Winter' method. WBC, Lymphocyte and ESR were measured by heart puncture and CD4+ T cell, CD8+ T cell and CD4+/CD8+ T cell ratio were measured from the spleen tissue. Writhing syndrom was measured with Tail flick unit(UGO BASILE, Italy) in the experiments conducted to check the analgesic activity. The temperature of the paws of carrageenan-induced arthritic rats was measured by Laser thermometer. Rectal temperature was measured by Yeast's method in anti-febrile experiments. Immune response was measured by CD4+, CD8+ T cell ratio and CD4+/CD8+ T cell ratio. Results : 1. It was recognized that Gamichangbaek-san(Jiaweichangbai-san) decreased the increase rate of Paw Edema effectively with statistical significance. 2. It was recognized that Gamichangbaek-san(Jiaweichangbai-san) decreased WBC, Lymphocyte and ESR with statistically high significance. 3. It was recognized that Gamichangbaek-san(Jiaweichangbai-san) did not show significant analgesic effect, but the Pressure pain threshold of the paws was increased with statistical significance. 4. It was recognized that Gamichangbaek-san(Jiaweichangbai-san) decreased rectal temperature effectively and had an anti-febrile effect about the febrile of a joint with statistical significance. 5. It was recognized that Gamichangbaek-san(Jiaweichangbai-san) increased CD4+ T cell ratio with statistically high significance and increased CD+8 T cell ratio with statistical non significance but increased CD4+/CD8+ T cell ratio effectively with statistical significance, too. Conclusions : According to the above results, it can be concluded Gamichangbaek-san(Jiaweichangbai-san) showed the treatment effects on the artificial arthritis resulted from carageenan in rats and it is suggested that more interest and study in the security for the clinical use were needed.

• 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.

• The Korean Journal of Pharmacology
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• v.31 no.1 s.57
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• pp.17-26
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• 1995

The present studies were carried out to determine if antinociceptive action of morphine and ${\beta}-endorphin$ administered intraventricularly was changed in. pentobarbital anesthetized spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. Antinociception was assessed by the tail-flick test. The $ED_{50}$ values of antinociception for morphine administered intraventricularly were 1.9 and 1.2 nmol for WKY and SHR rats, respectively. The $ED_{50}$ values of antinociception for ${\beta}-endorphin$ administered intraventricularly were 0.40 and 0.12 nmol for WKY and SHR rats, respectively. The $[Met^5]-enkephalin$ (ME) and proenkephalin mRNA levels in midbrain, pons and medulla, or lumbar section of the spinal cord in WKY and SHR rats were measured by the radioimmunoassay and Northern blot assay, respectively. There were no differences of ME and proenkephalin mRNA levels in these tissues between WKY and SHR rats. The results suggest that ${\beta}-endorphin$ but not morphine administered intraventricularly produces a greater antinociception in SHR rats. This increased antinociceptive effect of ${\beta}-endorphin$ in SHR rats may be not, at least, due to the alterations of ME And proenkephalin mRNA levels in the midbrain, pons and medulla, or spinal cord.

• 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.