• Journal of Acupuncture Research
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• 제21권6호
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• pp.51-62
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• 2004

Objective: To investigate the analgesic effect and its serotonergic mechanism, especially related with 5-HTI and 5-HT2 receptor, of electroacupuncture(EA) in the rat model of collagen-induced arthritis(CIA). Methods : Immunization of male Sprague-Dawley rats with bovine type II (C II) 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 spiroxatrine (5-HT1 receptor antagonist, 1mg/kg, intraperitoneal) and spiperone (5-HT2 receptor antagonist, 1 mg/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 by pretreatment of spiroxatrine and spiperone in CIA. Conclusions : Jogsamni($ST_{36}$) EA showed analgesic effects in CIA The analgesic effects of Jogsamni($ST_{36}$) EA were inhibited by spiroxatrine and spiperone pretreatment. These observations suggest that 5-HT1 and 5-HT2 serotonergic receptor, which involve the release of serotonin neurotransmitter, play an important roles in analgesic mechanism of EA stimulation.

• 대한한의학회지
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• 제26권3호
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• pp.239-248
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• 2005

Objectives : Electroacupuncture (EA)-induced analgesia has been known to be mediated through the activation of opioid, noradrenergic and serotonergic receptors. However, little study on serotonergic mechanism has been performed in an animal model of chronic pain. The present study was designed to elucidate the type of serotonergic receptors responsible for EA analgesia in the chronic pain model. Methods : In rats with complete Freund's: adjuvant-induced inflammation and spinal nerve injury, spinal wide dynamic range (WDR) cell responses to graded electrical stimulation of afferent C fiber were recorded before and after spinal application of selective 5-hydroxytryptamine (5-HT) receptor antagonists. EA stimulation (2Hz, 0.5msec, 3mA) was applied to the contralateral Zusanli point for 30 min. Results : In both models of chronic pain, WDR cell responses were greatly inhibited after EA stimulation. EA-induced inhibition of WDR celt responses was significantly attenuated by spinal application of non-selective 5-HT receptor antagonist, dihydroergocristine Of 5-HT receptor antagonists tested, 5-HT1A (WAY 100635) and 5-HT2 (LY53857) receptor antagonists strongly reduced an ability of EA stimulation to inhibit WDR cell responses. However, 5-HT1B (GR55562) and 5-HT3 (LY278584) receptor antagonists also had weak but significant blocking action on EA-induced inhibitory effect on chronic pain. Conclusions : Dorsal hem cell responses, afferent C fiber stimulation, chronic pain, electroacupuncture, serotonergic receptors.

• The Korean Journal of Physiology and Pharmacology
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• 제15권5호
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• pp.307-312
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• 2011

It has been rereported that axons which display 5-hydroxytryptamine (5-HT) immunoreactivity are abundant in the pancreas and the majority of serotonergic axons terminate within intrapancreatic ganglia, islet and acini. This histological result strongly suggests that intrapancreatic serotonergic nerves could affect to the pancreatic endocrine and exocrine secretion. Thus, this study was aimed to investigate whether intrapancreatic serotonergic nerves could affect pancreatic exocrine secretion and an action mechanism of the intrapancreatic serotonergic nerves. The rats were anesthetized with a single injection of urethane. The median line and the abdominal aorta was carefully dissected and cannulated with PE-50 tubing just above the celiac artery, and then tightly ligated just below the superior mesenteric artery. The pancreatic duct was also cannulated with Tygon microbore tubing. With the addition of serotonin, pancreatic volume flow and amylase output were significantly inhibited electrical field stimulation (EFS). On the other hand, pancreatic volume flow and amylase output were significantly elevated in EFS with the addition of spiperone. EFS application, however, pancreatic volume flow and amylase output had no significant change in cholecystokinin (CCK) alone when serotonin was applied under a 5.6 mM glucose background. Pancreatic volume flow and amylase output under 18 mM glucose background were significantly elevated in CCK plus serotonin than in CCK alone. These data suggest that intrapancreatic serotonergic nerves play an inhibitory role in pancreatic exocrine secretion and an important role in the insulin action or release.

• Biomolecules & Therapeutics
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• 제11권4호
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• pp.214-223
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• 2003

Methamphetamine (METH) and 3,4-methylenedioxymethamphetamine (MDMA) have become popular recreational drugs of abuse in many countries. Although the neurotoxic damage caused by METH and MDMA is characterized by degeneration of the dopaminergic and serotonergic systems in brain, the molecular and cellular mechanisms remain to be clarified. Therefore, the purposes of this study were to confirm the capability of METH and MDMA to induce apoptosis and to clarify the action of its molecular mechanism by using serotonergic JAR cells and dopaminergic SK-N-SH cells. METH and MDMA were dose-dependently cytotoxic to human serotonergic JAR cells and dopaminergic SK-N-SH cells. The morphological change of apoptosis was found in Giemsa staining and TUNEL and further verified in DNA fragmentation analysis. Immunoblotting analysis revealed proteolytic cleavage of caspase-3 and -9 and change of bcl-2 and bax proteins. These results suggest that METH and MDMA may induce caspase-dependent apoptosis via the mitochondrial cell death pathway and METH and MDMA-induced neurotoxicity may happen to broadly and independently of both dopaminergic and serotonergic systems.

• Journal of Acupuncture Research
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• 제23권3호
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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 $5-HT_4$.

• The Korean Journal of Pain
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• 제24권4호
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• pp.179-184
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• 2011

Background: The analgesic mechanisms of cyclooxygenase (COX)-2 inhibitors have been explained mainly on the basis of the inhibition of prostaglandin biosynthesis. However, several lines of evidence suggest that their analgesic effects are mediated through serotonergic or adrenergic transmissions. We investigated the roles of these neurotransmitters in the antinociception of a selective COX-2 inhibitor at the spinal level. Methods: DUP-697, a selective COX-2 inhibitor, was delivered through an intrathecal catheter to male Sprague-Dawley rats to examine its effect on the flinching responses evoked by formalin injection into the hindpaw. Subsequently, the effects of intrathecal pretreatment with dihydroergocristine, prazosin, and yohimbine, which are serotonergic, ${\alpha}1$ adrenergic and ${\alpha}2$ adrenergic receptor antagonists, respectively, on the analgesia induced by DUP-697 were assessed. Results: Intrathecal DUP-697 reduced the flinching response evoked by formalin injection during phase 1 and 2. But, intrathecal dihydroergocristine, prazosin, and yohimbine had little effect on the antinociception of intrathecal DUP-697 during both phases of the formalin test. Conclusions: Intrathecal DUP-697, a selective COX-2 inhibitor, effectively relieved inflammatory pain in rats. Either the serotonergic or adrenergic transmissions might not be involved in the analgesic activity of COX-2 inhibitors at the spinal level.

• Archives of Pharmacal Research
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• 제13권1호
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• pp.55-63
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• 1990

An attempt was made to investigate the effect of intracerebroventricular 5-hydroxytrypatamine (5-HT) on the cardiovascular system in urethane-anesthetized rabbit and to elucidate the mechanism of its action. 5-HT given into a lateral ventricle caused clearly a dose-dependent decrease inboth arterial blood pressure and in heart rate. The bradycardia and hypotension induced by 5-HT were significantly attenuated by the prior injection of ketanserin, cyproheptadine or clonidine. Pretreatment of atropine with bilateral vagotomy did not affect both bradycardia and hypotension. Propranolol weakened markedly the breadcardia of 5-HT but did not influence the depressor response of 5-HT. These experimental results suggest that intraventricular 5-HT cause the hypotension and bradyardia in rabbits through the stimulation of serotonergic receptors in brain, which is seemed to be associated to inhibition of sympathetic tone.

• Biomolecules & Therapeutics
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• 제20권6호
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• pp.506-512
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• 2012

Although pruritus is the critical symptom of atopic dermatitis that profoundly affect the patients' quality of life, controlling and management of prurirtus still remains as unmet needs mainly due to the distinctive multifactorial pathogenesis of pruritus in atopic dermatitis. Based on the distinct feature of atopic dermatitis that psychological state of patients substantially influence on the intensity of pruritus, various psychotropic drugs have been used in clinic to relieve pruritus of atopic dermatitis patients. Only several psychotropic drugs were reported to show real antipruritic effects in atopic dermatitis patients including naltrexone, doxepin, trimipramine, bupropion, tandospirone, paroxetine and fluvoxamine. However, the precise mechanisms of antipruritic effect of these psychotropic drugs are still unclear. In human skin, serotonin receptors and serotonin transporter protein are expressed on skin cells such as keratinocytes, melanocytes, dermal fibroblasts, mast cells, T cells, natural killer cells, langerhans cells, and sensory nerve endings. It is noteworthy that serotonergic drugs, as well as serotonin itself, showed immune-modulating effect. Fenfluramine, fluoxetine and 2, 5-dimethoxy-4-iodoamphetamine significantly decreased lymphocyte proliferation. It is still questionable whether these serotonergic drugs exert the immunosuppressive effects via serotonin receptor or serotonin transporter. All these clinical and experimental reports suggest the possibility that antipruritic effects of selective serotonin reuptake inhibitors in atopic dermatitis patients might be at least partly due to their suppressive effect on T cells. Further studies should be conducted to elucidate the precise mechanism of neuroimmunological interaction in pruritus of atopic dermatitis.

• Journal of Acupuncture Research
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• 제22권2호
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• pp.19-32
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• 2005

Objectives : to evaluate the analgesic effect of bee venom acupuncture on Choksamni (ST36) in the collagen-induced arthritis rats and investigate the role played by serotonergic receptor subtypes (5-HT1a, 5-HT2a) in the antinociceptive effect of bee venom acupuncture in a thermal hyperalgesia test Methods : Experiments were performed on 5 week-aged 60 male Sprague-Dawley rats according to National Institute of Health guidelines and the ethical guidelines of the International Association for the Study of Pain (IASP). Arthritis was induced with arthrogenic collagen emulsion (Bovine type II collagen ${\mu}g$ with incomplete Freund's adjuvant $100\;{\mu}g$). The onset of arthritis was considered to be present when erythema and swelling were detected in at least one joint. The thermal hyperalgesia was evaluated weekly with tail flick test in the rats of severity grade 3 without any injury at tail and foot (including inflammation, ulceration, snap). In the fourth week after first immunization, the analgesic effect of bee venom acupuncture (Choksamni, ST36) was measured with consecutive tail flick latency after intraperitoneal injection of spiroxatrine (1mg/kg) and spiperone (1mg/kg). Results : Chronic inflammatory pain was induced as time elapsed after the immunization of arthrogenic collagen and the maximum value was reached from third to fifth week. Chronic inflammatory pain induced by CIA was inhibited by bee venom acupuncture on the left ST36. The analgesic effect of bee venom acupuncture was inhibited by intraperitoneal injection of 5-HT1a antagonist spiroxatrine and 5-HT2a antagonist spiperone. Conclusions : Therefore, a conclusion. that the analgesic effect of bee venom acupuncture in the chronic inflammatory pain is partially mediated by 5-HT1a and 5-HT2a receptors can be made.

• 대한약리학회지
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• 제25권1호
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• pp.1-11
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• 1989

혈압 및 심박동수 조절에 대한 serotonin성 기전의 역할을 흰쥐 뇌의 NTS에서 검토하고 catecholamine성 기전과 비교하여 다음과 같은 결과를 얻었다. 1) 5-HT를 NTS에 주사시 혈압 및 심박동수는 감소되었고, 5-HT 300 pmol을 NTS에 주사하였을 때 가장 현저하게 하강하였다. ${\alpha}-MNE$과 clonidine도 마찬가지로 혈압과 심박동수의 감소를 일으켰다. 5-HT의 효과는 5-HT 수용체 길항제인 ritanserin, methysergide 및 ketanserin의 전처치에 의하여 봉쇄되었다. 2) Reserpine과 6-OHDA를 전처치하였을 때는 5-HT에 의한 혈압 및 심박동수 감소가 현저하게 약화되었다. 3) 5,7-DHT 전처치 후에는 5-HT에 의한 혈압 및 심박동수 감소는 증가하였다. 한편 6-OHDA 전처치에 의하여서도 clonidine의 혈압 및 심박동수 감소 현상은 항진하였다. 4) 5,7-DHT와 6-OHDA를 i.c.v.로 전처치하였을 때 phenylephrine과 sodium nitropursside에 의한 압반사 감수성은 현저히 저하하였고, 이들을 NTS로 주사시도 압반사 감수성이 손상되었다. 5) Immunohistochemistry에 의해 NTS에서 catecholamine성 세포체, 신경축색 말단과 serotonin성 신경축색 말단을 관찰하였고, 6-OHDA 주사후에 catecholamine성 신경축색 말단의 varicosity는 현저히 감소하였다. 한편 5,7-DHT처치에 의하여서는 serotonin성 신경축색 말단의 varicosity가 현저히 감소하였다. 이상의 실험 결과, NTS에 있는 serotonin성 수용체의 활성에 의하여 (1) 혈압 및 심박동수 감소가 일어나며, (2) 이는 catecholamine성 신경계와 관련되어 야기되며, (3) serotonin과 catecholamine성 수용체는 NTS의 postsynaptic site에 존재하고, (4) serotonin과 catecholamine성 신경세포는 압반사 조절에 있어서 중요한 역할을 하는 것으로 사료된다.