• Journal of Acupuncture Research
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• v.20 no.1
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• pp.35-50
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• 2003

In order to study the effect of Bee venom(BV) on the subarachnoid hemorrhage animal model, the autologous whole blood was applied to the vicinity of the sprague dawley rat right femoral artery. Following periarterial application of autologous whole blood(PAB) and intraperitoneal injection of BV(1:5,000 nd 1:500), the vasomotor responses to BV(from 1:500,000 to 1:500) were identified and the histological changes, neovascularized blood vessel were observed. We have shown that alterations in vasomotor and histological findings are elicited following application of periarterial blood and i.p. injection of BV(1:5,000 and 1:500) induced heavy vasospasm and neovascularization on the subarachnoid hemorrhage like model form peripheral artery.

• Journal of Pharmacopuncture
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• v.4 no.3
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• pp.7-14
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• 2001

Objective: This study was done to observe the effects on the thermal changes and side effects of Bee Venom acupuncture. The objectives are as follows; If there are remarkable local thermal changes between pre and post Bee Venom acupuncture therapy on D.I.T.I. or not. If there are those, we examine how long it' s changes are maintained, what is the adequate interval on Bee Venom acupuncture therapy, and what the reactions in a local or whole body are on that therapy. Methods: To study the local thermal changes in Bee Venom acupuncture therapy, D.I.T.I. was used. Determination of this analysis periods are pre and post-therapy(5 minutes, 1 hour, 1day,2days, 3days, 5days and 7days later). The study group was divided into two groups. One was BV group(N=19), another was NS(Normal Saline) group. The Bee Venom acupuncture was injected by 0.2ml divided into 0.05ml at the Fengmen(風門:12), Feishu(肺兪:B13), Fufen(附分:B41), Pohu(魄戶: B42) 4 points. Then, in order to analyze the clinical form, we have observed responses of 23 students whenever we checked the thermal changes of their after performing. Results: The following results were obtained. 1. In BV group, there was a significant dermatothermal difference between pre and post therapy. That difference was most remarkable in post-therapy 1 hour to lday, and was not remarkable in post-therapy 5-7days later. 2. There was no significant dermatothermal changes at NS group, but BV group had remarkable changes between operated and non operated area in post-therapy 1hour, 1day, 2days. But there was none 7 days later. 3. Among the physical reactions after Bee Venom acupuncture therapy, operated-area pain, itching, pain on moving and fatigue sign most appeared until post-therapy 3days. Itching and fatigue sign appeared until post-therapy 7days. 4. In comparison the dermatothermal changes with the physical reactions, the decrease of { CT = (Rt Temperature -Lt. Temperature) / Rt. $Temperature{\times}100$} and the disappearance of physical reactions were about the same.

• The Korean Journal of Physiology and Pharmacology
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• v.8 no.5
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• pp.281-288
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• 2004

The present study was undertaken to confirm whether melittin, a major constituent of whole bee venom (WBV), had the ability to produce the same nociceptive responses as those induced by WBV. In the behavioral experiment, changes in mechanical threshold, flinching behaviors and paw thickness (edema) were measured after intraplantar (i.pl.) injection of WBV (0.1 mg & 0.3 mg/paw) and melittin (0.05 mg & 0.15 mg/paw), and intrathecal (i.t.) injection of melittin $(6{\mu}g)$. Also studied were the effects of i.p. (2 mg & 4 mg/kg), i.t. $(0.2{\mu}g\;&\;0.4{\mu}g)$ or i.pl. (0.3 mg) administration of morphine on melittin-induced pain responses. I.pl. injection of melittin at half the dosage of WBV strongly reduced mechanical threshold, and increased flinchings and paw thickness to a similar extent as those induced by WBV. Melittin- and WBV-induced flinchings and changes in mechanical threshold were dose- dependent and had a rapid onset. Paw thickness increased maximally about 1 hr after melittin and WBV treatment. Time-courses of nociceptive responses induced by melittin and WBV were very similar. Melittin-induced decreases in mechanical threshold and flinchings were suppressed by i.p., i.t. or i.pl. injection of morphine. I.t. administration of melittin $(6{\mu}g)$ reduced mechanical threshold of peripheral receptive field and induced flinching behaviors, but did not cause any increase in paw thickness. In the electrophysiological study, i.pl. injection of melittin increased discharge rates of dorsal horn neurons only with C fiber inputs from the peripheral receptive field, which were almost completely blocked by topical application of lidocaine to the sciatic nerve. These findings suggest that pain behaviors induced by WBV are mediated by melittin-induced activation of C afferent fiber, that the melittin-induced pain model is a very useful model for the study of pain, and that melittin-induced nociceptive responses are sensitive to the widely used analgesics, morphine.

• Journal of Acupuncture Research
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• v.18 no.5
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• pp.33-42
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• 2001

Objective : To evaluate the effect of treatment for Rheumatoid arthritis by using Bee-venom Acupuncture that is well known for anti-inflammatory effect and function of activating immune system. Methods : Evaluated the result of Bee-venom Acupuncture treatment twice in a week for patients who diagnosised as rheumatoid arthritis by 7 criteria of US Rheumatism Academy. Results : 1. If you see the distribution chart, sexual rate of male and female was 1:2.75 and age distribution shows as age ascend it shows high. 2. If you see the duration distribution, it shows chronic tendency in order of more than 6 months (59.5%), 2 to 5 months, and 1 month. 3. If you see the invaded region distribution, it shows chronic tendency in order of finger(17 cases), wrist joint(16 cases), knee joint(16 cases), ankle joint(10 cases), elbow joint(8 cases), shoulder joint(7 cases), feet(7 cases), hip joint(5 cases), low back(3 cases) and neck(2 cases). 4. If you see the result of duration distribution treatment, the improvement index is rising in order of within a month, 2 to 5 months, and over 6 months. So it shows that it has good result of treatment within a month. 5. If you see the invaded region, it shows high improvement index in order of low back, hop joint, shoulder joint, wrist joint, feet, knee joint, finger, elbow joint, ankle joint and neck. 6. If you see the result of morning stiffness time before treatment, it shows good effect of treatment in order of 2-3hrs, 30min.-an hr, an hr to 2hrs, and 0-30min. 7. If you see the patients satisfaction after Bee-venom Acupuncture treatment, Excellent is 6 cases, Good is 7 cases, and Moderate 2 cases. Conclusions : It will have greater treatment effect if herbal medicine, moxibustion, and acupuncture are used together as patients whole body condition and symptoms with Bee-venom Acupuncture for rheumatoid arthritis that is chronic inflammatory disease.

• The Korean Journal of Physiology and Pharmacology
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• v.9 no.3
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• pp.179-186
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• 2005

Whole bee venom (WBV) and its major component, melittin, have been reported to induce long-lasting spontaneous flinchings and hyperalgesia. The current study was designed to elucidate the peripheral and spinal mechanisms of N-methyl-D-aspartate (NMDA) and non-NMDA receptors by which intraplantar (i.pl.) injection of WBV and melittin induced nociceptive responses. Changes in mechanical threshold and flinching behaviors were measured after the injection of WBV (0.04 mg or 0.1 mg/paw) and melittin (0.02 mg or 0.05 mg/paw) into the mid-plantar area of a rat hindpaw. MK-801 and CNQX (6-cyano-7-nitroquinoxaline-2,3-dione disodium) were administered intrathecally (i.t. $10{\mu}g$) or i.pl.($15{\mu}g$) 15 min before or i.t. 60 min after i.pl. WBV and melittin injection. Intrathecal pre- and postadministration of MK-801 and CNQX significantly attenuated the ability of high dose WBV and melittin to reduce paw withdrawal threshold (PWT). In the rat injected with low dose, but not high dose, of WBV and melittin, i.pl. injection of MK-801 effectively suppressed the decrease of PWTs only at the later time-points, but the inhibitory effect of CNQX (i.pl.) was significant at all time-point after the injection of low dose melittin. High dose WBV- and melittin-induced spontaneous flinchings were significantly suppressed by i.t. administration of MK-801 and CNQX, and low dose WBV- and melittin-induced flinchings were significantly reduced only by intraplantarly administered CNQX, but not by MK-801. These experimental flinchings suggest that spinal, and partial peripheral mechanisms of NMDA and non-NMDA receptors are involved in the development and maintenance of WBV- and melittin-induced nociceptive responses.

• Journal of Pharmacopuncture
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• v.4 no.1
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• pp.65-84
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• 2001

We recently demonstrated that bee venom (BV) injection into acupoint (i.e. Zusanli) produced more potent anti-inflammatory and antinociciptive effect in Freunds adjuvant induced rheumatoid arthritis (RA) model as compared with that of non-acupoint injection(i.e back). However, the precise components underlying BV-induced antinociceptive and/or anti-inflammatory effects have not been fully understood. Therefore, we further investigated the anti-arthritic effect of BV after extracting the whole BV according to solubility (water soluble: BVA, ethylacetate soluble: BVE). Subcutaneous BVA treatment (0.9 mg/kg/day) into Zusanli acupoint was found to dramatically inhibit paw edema and radiological change (i.e. new bone proliferation and soft tissue swelling) caused by Freunds adjuvant injection. In addition, the increase of serum interleukin-6 by RA induction was normalized by the BVA treatment as similar with that of non-arthritic animals. On the other hand, BVA therapy significantly reduced arthritis induced nociceptive behaviors (i.e., nociceptive score for mechanical hyperalgesia and thermal hyperalgesia). Furthermore, BVA treatment significantly suppressed adjuvant induced Fos expression in the lumbar spinal cord at 3 weeks post-adjuvant injection. However, BVE treatment (0.05 mg/kg/day) has not any anti-inflammatory and anti-nociceptive effect on RA. Based on the present results, we demonstrated that BVA might be a effective fraction in whole BV for long-term treatment of RA-induced pain and inflammation. However, it is clear necessary that further fraction study about BVA was required for elucidating an effective component of BVA.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.151.2-152
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• 2003

Bee venom (BV) has been utilized to relieve pain and to treat inflammatory diseases such as rheumatoid arthritis (RA). BV contains a variety of different peptides including melittin, apamin, adolapin and mast cell degranulating (MCD) peptide. In addition, it also contains enzyme (i.e. phospholipase A2), biologically active amines and non-peptide components. (omitted)

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.2
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• pp.365-371
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• 2006

Bee Venom aqua-acupuncture (BVA) simultaneously exerts pharmacological effects of biologically active compounds, existed in the whole bee venom, and medicinal effect of the stimulation of acupuncture points. BVA has been considered as a promising therapeutic method for treating various chronic diseases, mainly accompanying severe pain and inflammation. As a painless injection device, jet injectors have been commercially marketed for various clinical applications including insulin injection and vaccination. Among them, a pressure-driven jet injector system could be used for intradermal delivery of a variety of drugs. The aim of this study was to investigate the analgesic effects of the BVA using a needle-free injector (Biojector $2000^{\circledR}$, Bioject Inc., OR, USA), compared to the conventional BV aqua-acupuncture using a typical syringe. Adult Sprague-Dawley rats were injected with bee venom $(0.08mg/kg,\;50{\mu}l)$ using Biojector $2000^{\circledR}$ (BVA-B) or a syringe (BVA-5) into the Zusanli (ST36) acupoint, 30 minutes before plantar injection of 2% formalin. It was found that BVA-B-, or BVA-5-treated rats, compared to controls, exhibited significantly less licking behavior during the late phase in the rat formalin test, when compared to controls. During early phase, however, those effects were not significant but substantial. The analgesic effect of BVA-B was also compatible with that of the conventional BVA-5. In the immunohistochemical studies, BVA-B significantly suppressed the expression of formalin-evoked c-fos, a biomarker of neuronal activity, in the lumbar dorsal horn of the spinal cord. These results indicated that BVA-B waseffective in the modulation of pain in the rat formalin test, compared to BVA-5. Taken together, the needle-free jet injector system could be substituted for the conventional aqua- acupuncture with the advantage of little pain.

• The Korean Journal of Physiology and Pharmacology
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• v.10 no.6
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• pp.297-302
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• 2006

Melittin, a major component of bee venom, produces a sustained decrease in mechanical threshold, and an increase in spontaneous flinchings and paw thickness, which are characteristics similar to those induced by whole bee venom. Melittin-induced nociception has been known to be modulated by the changes in the activity of excitatory amino acid receptors, voltage-dependent calcium channels, cyclooxygenase and serotonin receptors. The present study was undertaken to investigate the role of calcium chelators (TMB-8 & Quin 2) in melittin-induced nociceptive responses. Changes of mechanical threshold and spontaneous flinching behaviors were measured at a given time point following intraplantar injection of melittin ($30{\mu}g/paw$). Intrathecal or intraplantar pre-administration and intrathecal posttreatment of TMB-8 and Quin 2 significantly prevented the melittin-induced reduction of mechanical threshold, and intraplantar or intrathecal pre-treatment of TMB-8 and Quin 2 suppressed melittininduced flinching behaviors. These results indicate that calcium ion in the spinal dorsal horn neurons and peripheral nerves plays an important role in the production and maintenance of mechanical allodynia and spontaneous pain by melittin.

• Journal of Veterinary Clinics
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• v.24 no.4
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• pp.499-502
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• 2007

The study was performed to assess the antinociceptive efficacy of Korean bee venom(BV) in the rat formalin test. Korean BV was collected using BV collector devices in which an electrical impulse is used to stimulate the worker bee(Apis mellifera L.) to sting and release venom. After collection, whole Korean BV was evaporated until dry using BV collector. Experiments were performed on male Sprague-Dawley rats(weighing 260-270, 6 weeks old). Rats divided into 4 groups, each comprising 8 rats. BV was diluted and amounts of 6 mg/kg body weight(BW), 0.6 mg/kg BW and 0.06 mg/kg BW were tested. BV was subcutaneously injected to produce an antinociceptive effect and the antinociceptive efficacy was evaluated using a rat formalin test. BV was subcutaneously injected into an acupoint(Zusanli, ST36) at 15 min prior to 1% formalin($50{\mu}l$) injection. The antinociceptive effect observed during 60 min following formalin administration. BV produced antinociceptive efficacy from 10 to 60 min after formalin injection. The antinociceptive efficacy of Korean BV showed a dose-dependent response. These results suggest that Korean BV may be a suitable and preferred choice for antinociceptive efficacy in pain management.