• Journal of Veterinary Clinics
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• v.27 no.6
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• pp.674-678
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• 2010

The effects of medetomidine on the degree of analgesia and sedation in rats were evaluated. The rats were randomly divided into six groups: saline, 1 mL/kg (group 'Saline'); butorphanol, 2.0 mg/kg; medetomidine, 0.2, 0.4, 0.8 or 1.6 mg/kg (group 'MED0.2', 'MED0.4', 'MED0.8' and 'MED1.6', respectively). The degree of analgesia was measured in the $50^{\circ}C$ hot-water tail-flick latency test, and the degree of sedation was evaluated using the numerical sedation score (NSS) and the righting reflex. All doses of medetomidine, except MED0.2, significantly increased the analgesic effect compared to the Saline group. Variables in the MED0.4 and MED0.8 groups, but not in the MED1.6 group, were significantly increased compared to those in the MED0.2 group. However, analgesia with all doses of medetomidine was not significantly different compared to that with butorphanol. Saline and butorphanol treatments did not induce sedation and loss of righting reflex during the recording period. NSS in the MED0.4, MED0.8 and MED1.6 groups were significantly higher than that in the MED0.2 group. NSS in the MED0.8 and MED1.6 groups were not significantly different from that in the MED0.4 group. The latency to loss of righting reflex in the MED0.8 and MED1.6 groups decreased significantly compared to that in the MED0.2 group. Thus, 0.4 and 0.8 mg/kg of medetomidine provided not only reliable analgesia but also sedation to rats. In conclusion, 0.4 to 0.8 mg/kg medetomidine could be a useful chemical restraint method in rats.

• Journal of Acupuncture Research
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• v.21 no.2
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• pp.115-129
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• 2004

Objectives : To investigate the analgesic effect and its cholinergic mechanism of electroacupuncture(EA) in the rat model of collagen-induced arthritis(CIA). Methods : Immunization of male Sprague-Dawley rats with bovine typeII (CII) collagen emulsified in Freund's incomplete adjuvant, followed by a booster injection 14 days later, leads to development of arthritis in more than 70% of rats by 21 days postinjection. After three weeks of first immunization, EA stimulation(2 Hz, 0.07 mA, 0.3 ms) was delivered into Jogsamni($ST_{36}$) for 30 minutes. Analgesic effect was evaluated by tail flick latency(TFL). We compared the analgesic effect of EA with TFLs between pretreatment of normal saline and pretreatment of Atropine (1 mg/kg, intraperitoneal) and Neostigmine ($100{\mu}g/kg$, intraperitoneal) in CIA. Results : 1. TFLs were gradually decreased in CIA as increasing severity of arthritis. 2. Jogsamni($ST_{36}$) EA stimulation in CIA increased TFLs and the effect lasted for 60 minutes. 3. Increased TFLs with Jogsamni($ST_{36}$) EA stimulation were inhibited with pretreatment of atropine in CIA 4. Increased TFLs with Jogsamni($ST_{36}$) EA stimulation did not show an obvious synergistic effect with pretreatment of neostigmine in CIA. Conclusions: Jogsamni($ST_{36}$) EA showed analgesic effects in CIA. The analgesic effects of Jogsamni($ST_{36}$) EA were inhibited by atropine pretreatment and combined application of Jogsamni(ST36) EA and neostigmine did not show an synergistic effect. These observations suggest that intrinsic muscarinic cholinergic pathways represent an important modulating system in pain perception of inflammatory pain in CIA It is suggested that, the active mechanism of analgesic effect in EA may involve the release of acetylcholine in the spinal cord.

• Journal of Acupuncture Research
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• v.22 no.1
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• pp.99-108
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• 2005

Objective : The aim of this study is to investigate the analgesic effect and its mechanism of bee venom acupuncture on collagen-induced arthritis(CIA) rats. Methods : Bee venom (1 mg/kg) was subcutaneously punctured into Choksamni (ST36) of CIA Analgesic effect was evaluated by using the tail flick latency (TFL). Opioid and ${\alpha}2$-adrenergic neurotransmitter system were examined by naloxone as an opioid receptor antagonist and yohimbine as ${\alpha}2$-adrenoceptor antagonist prior to bee venom cupuncture. Results : The results were as follows; 1. The TFL for the CIA rat was decreased as time went by. 2. The TFL in CIA rat was increased in bee venom acupuncture group compared with control group (no treatment). 3. Analgesic effect of bee venom acupuncture was not abolished by naloxone pre-treatment in the CIA rat. 4. Analgesic effect of bee venom aqua-acupuncture was abolished by yohimbine pre-treatment in the CIA rat. 5. Two weeks bee venom acupuncture had the continous analgesic effect for 4 weeks. Conclusions : Bee venom acupuncture has an analgesic effect on the CIA rat and has an antinociception mediated by ${\alpha}2$-adrenergic system.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.3
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• pp.191-198
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• 2010

The effects of different doses of tramadol on analgesia and electroencephalographic (EEG) spectralparameters were compared in rats. Saline or tramadol 5, 10, 20 or 40 mg/kg was administered. The degree of analgesia was evaluated by tail-flick latency, and the degree of seizure was measured using numerical seizure score (NSS). Additionally, band powers, median power frequency and spectral edge frequency 95 were measured to quantify the EEG response. All doses of tramadol produced spike-wave discharge. Tramadol significantly and dose-dependently increased the analgesia, but these effects did not correspond with the changes in the EEG spectral parameters. NSS significantly increased in the Tramadol 20 and 40 mg/kg treatment groups compared to the Control and TRA5 groups, and two rats given 40 mg/kg had convulsions. In conclusion, tramadol dose-dependently increased the analgesic effect, and the 10 mg/kg dose appears to be a reliable clinical dose for analgesia in rats, but dose-dependent increases in analgesia and seizure severity did not correlate with EEG spectral parameters.

• The Journal of Korean Physical Therapy
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• v.16 no.2
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• pp.181-194
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• 2004

The aim of this study was to investigate the effects of TENS and cold application on secondary thermal hyperalgesia in rats induced by muscle pain. Muscle pain was induced in male Sprague-Dowley rats by intra-muscular injection of gastrocnemius with $3\%$ carrageenan. The paw withdrawal latency(PWL) and tail flick test(TFT) to heat were used to detect secodary thermal hyperalgesia induced by the muscle pain. PWL and TFT were quantified before and 4, 10, and 24 h after induction of muscle pain and after application of TENS(100Hz, $100{\mu}s$, sensory intensity) and cold($4^{\circ}C$). TENS and cold significantly reduced the PWL and TFT to heat stimuli when compared with controls receiving no TENS and cold(p<.05). These results suggested that application of TENS and cold attributed to decrease secodary thermal hyperalgesia in rat induced by muscle pain.

• The Journal of Korean Physical Therapy
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• v.15 no.4
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• pp.190-198
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• 2003

Expression of c-fos, an immediate early gene, has accepted to be a marker of functional activity in neurons. This study was aimed to investigate the effects of cold therapy on the expression of spinal cord c-fos in rats of carrageenan-induced muscle pain. Muscle pain was induced in male Sprague-Dawley rats by intra-muscular injection of gastrocnemius with $2\%$ carrageenan. The paw withdrawal latency (PWL) and tail flick test (TFT) responses to heat stimuli were used to detect secondary hyperalgesia produced by the muscle pain and measured to assess the effects of cold. The expression of c-fos was determined in the lumbar regions of the spinal cord by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry assays. The secondary hyperalgesia to heat simuli (PWL and TFT) were significantly reduced in cold therapy compared with that in the controls. In RT-PCR assays the expression of c-fos mRNA was down-regulated in the lumbar spinal cord in cold group. In addition, Fos immunoreactivity in the dorsal horn of the lumbar spinal cord was decreased in cold group. These results suggested that application of cold attributed to increase PWL and TFT responses and to decrease expression of the c-fos produced by muscle pain.

• Journal of Acupuncture Research
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• v.24 no.2
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• pp.73-81
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• 2007

목적 : 본 연구는 화피의 연골 보호 및 소염 진통 작용을 알아보고, 화피를 이용한 관절염치료 약침액 개발의 기초자료를 얻기 위해 고안되었다. 방법 : In vitro에서는 토끼 무릎관절에서 배양된 연골조직에 5ng/ml IL-1${\alpha}$ 처리 후， 화피의 연골보호 효과, 연골세포에 대한 독성을 조사하였다. In vivo에서는 토끼 무릎관절내 collagenase를 주입, CIA 유발 후, 28일간 매일 토끼의 구강으로 화피, 증류수, CEX를 투여하였으며, 연골보호, 소염, 진통에 대한 측정을 하였다. 결과 : 화피는 proteoglican 및 collagen분해 억제, MMPs 활성 억제로 연골 보호 효과가 있었으며, 연골 세포에 대한 독성이 없었다. 소염작용은 PGE2 생산 억제 및 COX-2발현 억제, carrageenan 유발 쥐 모델에서의 부종 억제로 확인되었다. 진통작용은 tail flick test에서의 latency time 증가, formalin test에서의 염증성 통증억제로 나타났다. 결론 : 화피가 퇴행성관절염에 대한 연골 보호 효과 및 소염 진통 작용이 있으므로, 이를 근거로 약침액을 개발 응용하면 퇴행성관절염 치료에 활용될 수 있다고 사료된다.

• 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.17 no.6
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• pp.505-510
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• 2013

Electroacupuncture (EA) is a modified form of acupuncture that utilizes electrical stimulation. We previously showed that EA stimulated rats were divided into responders that were sensitive to EA and non-responders that were insensitive to EA based on the tail flick latency (TFL) test. The dopamine beta-hydroxylase (DBH) gene was more abundantly expressed in the hypothalamus of responder rats than non-responder rats. To determine whether overexpression of DBH gene expression in the hypothalamus modulate EA analgesia, we constructed a DBH encoding adenovirus and which was then injected into the hypothalamus of SD rats. Microinjection of DBH or control GFP virus into the hypothalamus had no changes on the basal pain threshold measured by a TFL test without EA treatment. However, the analgesic effect of EA was significantly enhanced from seven days after microinjection of the DBH virus, but not after injection of the control GFP virus. DBH expression was significantly higher in the hypothalamus of DBH virus injected rat than control GFP virus or PBS injected rats. Moreover, expression of the DBH gene did not affect the body core temperature, body weight, motor function or learning and memory ability. Although the functional role of DBH in the hypothalamus in the analgesic effect of EA remains unclear, our findings suggest that expression of the DBH gene in the hypothalamus promotes EA analgesia without obvious side-effects.

• Journal of Acupuncture Research
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• v.23 no.3
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• pp.77-90
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• 2006

Objectives : To evaluate the analgesic effect of electroacupuncture on Choksamni (ST36) in the collagen-induced arthritis rats and investigate the role played by serotonergic receptor subtypes $(5-HT_{1A},\;5-HT_{1B},\;5-HT_4)$ in the antinociceptive effect of electroacupuncture in the thermal hyperalgesia test. Methods : Immunization of male Sprague-Dawley rats with bovine type II collagen emulsified in incomplete Freund's adjuvant, followed by booster injection 14 days later induced collagen-induced arthritis (CIA). The thermal hyperalgesia was evaluated weekly with tail flick latency (TFL). In the fourth week after first immunization. EA stimulation (2Hz, 0.07mA, 0.3ms) was delivered into Choksamni for 20 minutes. We measured the analgesic effect of EA with TFL afer intraperitoneal injection of normal saline, WAYl00635, SB216641 and GR125487. Results : TFLs were gradually decreased in CIA as time elapsed after the immunization of arthrogenic collagen and the maximum value was reached from third to fifth week. EA stimulation on ST36 inhibited chronic inflammatory pain induced by CIA. The analgesic effect of EA was inhibited by pretreatment of $5-HT_{1A}$. antagonist (WAYl00635), $5-HT_{1B}$ antagonist (SB216641) and $5-HT_4$ antagonist (GR125487). Conclusion : Electroacupuncture has the analgesic effect on chronic inflammatory pain and its mechanism was mediated by $5-HT_{1A}$, $5-HT_{1B}$ and $5-HT_4$.