Article

Bee Stings—A Remedy for Postherpetic Neuralgia? A Case Report

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  • Folsom Pain Management
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Abstract

This case report describes the effects of bee stings on painful postherpetic neuralgia in a 51-year-old man. The patient was stung by 3 bees in the distribution in which he had been experiencing postherpetic neuralgia. One day after the bee stings, the patient's painful postherpetic neuralgia was completely relieved, and the relief lasted for 1 and a half months. Subsequently, the patient's pain returned, but at significantly less intensity and frequency than what he had experienced prior to the bee stings. Bee venom and bee sting therapy have been shown to have both antinociceptive and anti-inflammatory properties, which may explain why the bee stings relieved the patient's postherpetic neuralgia. Bee sting or bee venom therapy should be further investigated as a potential treatment modality for postherpetic neuralgia.

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... Its bioactive compounds include many peptides, enzymes, and amines and can effectively treat a variety of diseases, including idiopathic Parkinson's disease. [7][8][9][10] In 2007, Janik et al. 11 reported the case of a man whose PHN symptoms, refractory to all forms of treatment, were ultimately relieved by an accidental bee sting. This event, combined with prior knowledge of bee venom's analgesic effects, made it a viable candidate for therapeutic applicability. ...
... First, it differs from other case reports because it has further developed and reproduced a therapeutic method that was observed a few years earlier. 11 Despite the increasing number of bee venom studies on animals, there are few clinical reports of bee venom treatments conducted on humans. This case measured exact doses of bee venom, controlling the patient's treatment sessions as much as possible in order to lay a foundation for future large-scale experiments that could help delineate the BEE VENOM FOR POSTHERPETIC NEURALGIA exact mechanism of bee venom treatment, as well as specify which types of patients would be best suited for this treatment. ...
Article
Objective: Bee venom has been reported to have antinociceptive and anti-inflammatory effects in experimental studies. However, questions still remain regarding the clinical use of bee venom. This report describes the successful outcome of bee venom treatment for refractory postherpetic neuralgia. Patient: A 72-year-old Korean man had severe pain and hypersensitivity in the region where he had developed a herpes zoster rash 2 years earlier. He was treated with antivirals, painkillers, steroids, and analgesic patches, all to no effect. Intervention: The patient visited the East-West Pain Clinic, Kyung Hee University Medical Center, to receive collaborative treatment. After being evaluated for bee venom compatibility, he was treated with bee venom injections. A 1:30,000 diluted solution of bee venom was injected subcutaneously along the margins of the rash once per week for 4 weeks. Results: Pain levels were evaluated before every treatment, and by his fifth visit, his pain had decreased from 8 to 2 on a 10-point numerical rating scale. He experienced no adverse effects, and this improvement was maintained at the 3-month, 6-month, and 1-year phone follow-up evaluations. Conclusion: Bee venom treatment demonstrates the potential to become an effective treatment for postherpetic neuralgia. Further large-sample clinical trials should be conducted to evaluate the overall safety and efficacy of this treatment.
... It has been used since ancient times to treat arthritis, rheumatism, back pain, skin diseases and in this modern age as an alternative therapy to treat autoimmune diseases, Lyme disease and chronic fatigue syndrome [5][6][7]. Some reports have shown beneficial effects of bee venom in post herpetic neuralgia [8], fibromyalgia and multiple sclerosis [9]. Interleukin (IL) 1β, tumor necrosis factor alpha (TNFα), and IL-6 are cytokines which mediate cellular responses during immune activation and inflammation. ...
... In this study, there was a statistically significant improvement in patients regarding their immunity, their health and general conditions and this is in agreement to that explained by Park et al. and Prado et al. [29,30] that bee stings cause hemoconcentration which might be related to the marked edema induced by the venom. According to Janik et al. [8], course of treatment starts with testing the patient for allergy, which is known to occur in 1% of the general population. Bee venom is administered in the form of a direct bee sting or else by injection of a venom extract, and the treatment is usually given twice a week. ...
... Three bees stung the patient, and one day later, the patient's excruciating post-herpetic neuralgia was fully cured, lasting for one and a half months. The researchers concluded that more study into BV therapy as a viable therapeutic option for post-herpetic neuralgia should be conducted (Janik et al., 2007). New research done by specialists at the Korea Institute of Oriental Medicine suggested that cold allodynia, a kind of neuropathic pain, may be effective in treatment. ...
Article
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One of the most important insects in the world is Apis mellifera, which shows a critical role in different environmental conditions. For thousands of years, diverse honeybee products have been used to cure human ailments in many civilizations, and their curative effects have been mentioned in several holy books. The worker bees and queen produce an apitoxin, which is a cytotoxic and colorless liquid of hemotoxic bitter. The bee venom or apitoxin contains different sugars, volatile pheromones, phospholipids, enzymes, peptides, amino acids, minerals, proteins, and other bioactive compounds. The present review aims to collect more information about the history of honeybee venom and its medicinal uses. The apitoxin or bee venom is medicinally utilized to control different human diseases such as cancer, fibrotic disease, liver fibrosis, Parkinson disease, Alzheimer disease, arthritis, HIV, and Lyme disease. The first report on the application of bee venom to treat human ailments was published in 1888, when European clinical research was conducted to determine the efficacy of honeybee venom in treating rheumatic disorders. According to several studies published in different scientific journals, honeybee venom has been applied to control different human diseases for several centuries. Thus, it can be decided that bee venom can be a potential future biomedicine to control different diseases such as cancer.
... It has been used since ancient times to treat arthritis, rheumatism, back pain, skin diseases and in this modern age as an alternative therapy to treat autoimmune diseases, Lyme disease and chronic fatigue syndrome [8,9]. Some reports have shown beneficial effects of bee venom in postherpetic neuralgia [10], swine flu [11], fibromyalgia and multiple sclerosis [12]. There is no standardized practice for the administration of bee venom. ...
Article
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AIM: Multiple sclerosis (MS) is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged. We Study the effect of Apitherapy in treatment of MS. MATERIAL AND METHODS: Fifty patients with MS, their ages ranged between 26-71 years, were subjected to complete clinical and neurological history and examination to confirm the diagnosis. All cases were under their regular treatment they were divided into two main groups, Group I received honey, pollen, royal jelly and propolis and were treated with apiacupuncture 3 times weekly, for 12 months, in addition to their medical treatment, while group II remains on their ordinary medical treatment only. Apiacupuncture was done by bee stings for regulating the immune system. RESULTS: Results revealed that 4 patients showed some improvement regarding their defects in gait, bowel control, constipation and urination, while 12 cases, showed some mild improvement in their movement in bed, and better improvement in bed sores, sensation, and better motor power, only two cases of them were able to stand for few minutes with support. CONCLUSION: Although Apitherapy is not a curable therapy in MS, but it can be used to minimize the clinical symptoms of MS, and can be included among programs of MS therapy.
... Recently, various types of research on the treatment for specific diseases have been reported. For example, the efficacy of bee-venom pharmacopuncture for the treatment of arthritis was evaluated based on a literature search [9], and a clinical case report showed bee venom therapy to be a potential treatment modality for post-herpetic neuralgia [10]. Acupuncture plus point-injection for obstinate urticaria showed that the therapeutic effect in the treatment group was better than that in the control group [11]. ...
Article
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This paper reviews trends in research related to Korean pharmacopuncture therapy. Specifically, basic and clinical research in pharmacopuncture within the last decade is summarized by introducing categorical variables for classification. These variables are also analyzed for association. This literature review is based on articles published from February 1997 to December 2008 in a Korean journal, the Journal of the Korean Institute of Herbal Acupuncture, which was renamed the Journal of the Korean Pharmacopuncture Institute in 2007. Among the total of 379 papers published in the journal during this period, 164 papers were selected for their direct relevance to pharmacopuncture research and were categorized according to three variables: medicinal materials, acupuncture points and disease. The most frequently studied medicinal materials were bee-venom pharmacopuncture (42%), followed by meridian-field pharmacopuncture (24%), single-compound pharmacopuncture (24%), and eight-principle pharmacopuncture (10%). The frequency distributions of the acupuncture points and meridians for the injection of medicinal materials are presented. The most frequently used meridian and acupuncture point was the Bladder meridian and ST36, respectively. Contingency tables are also displayed to analyze the relationship between the categorized variables. Chi-squared analysis showed a significant association between the type of pharmacopuncture and disease. The trend in research reports on Korean pharmacopuncture therapy was reviewed and analyzed using a descriptive statistical approach to evaluate the therapeutic value of this technique for future research.
... It has been used since ancient times to treat arthritis, rheumatism, back pain, skin diseases and in this modern age as an alternative therapy to treat autoimmune diseases, Lyme disease and chronic fatigue syndrome [8,9]. Some reports have shown beneficial effects of bee venom in postherpetic neuralgia [10], swine flu [11], http://www.mjms.mk/ http://www.id-press.eu/mjms/ ...
Article
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AIM: Multiple sclerosis (MS) is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged. We Study the effect of Apitherapy in treatment of MS. MATERIAL AND METHODS: Fifty patients with MS, their ages ranged between 26-71 years, were subjected to complete clinical and neurological history and examination to confirm the diagnosis. All cases were under their regular treatment they were divided into two main groups, Group I received honey, pollen, royal jelly and propolis and were treated with apiacupuncture 3 times weekly, for 12 months, in addition to their medical treatment, while group II remains on their ordinary medical treatment only. Apiacupuncture was done by bee stings for regulating the immune system. RESULTS: Results revealed that 4 patients showed some improvement regarding their defects in gait, bowel control, constipation and urination, while 12 cases, showed some mild improvement in their movement in bed, and better improvement in bed sores, sensation, and better motor power, only two cases of them were able to stand for few minutes with support. CONCLUSION: Although Apitherapy is not a curable therapy in MS, but it can be used to minimize the clinical symptoms of MS, and can be included among programs of MS therapy.
... The patient was stung by three bees and one day after the bee stings, the patient's painful post-herpetic neuralgia was completely relieved, and the relief lasted for 1 and a half months. The researchers then suggested that BV therapy should be further investigated as a potential treatment modality for post-herpetic neuralgia [57]. ...
... Honey bee (Apis mellifera Linn.) venom has been utilized as pain reliever and as treatment against inflammatory diseases [7]. Moreover, Apitherapy, using live honey bee stings, have shown to have therapeutic value for pigs with respiratory diseases such as atrophic rhinitis and pleuropneumoniae [8]. Bee venom therapy is considered as a psychoneurological approach for auto-immune and nervous system diseases. ...
... It was stated that specific immunotherapy with bee venom can cause a nearly complete protection against allergic reactions from stings in most of patients (Severino et al. 2008). According to Janik et al., (2007) who found that bee venom was administered in the form of injection of a venom extract or a direct bee sting the same as design twice a week. It is claimed that bee venom therapy works with the patient's own body to decrease level of inflammation, as the stings produce inflammation; the body mounts an anti-inflammatory response Prado et al.,2010) ...
Article
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Chronic non-specific low back pain is considered to be the commonest medical symptom for which patients seek complementary and alternative medical treatment, including bee venom acupuncture. This study was done to detect the effect of bee venom acupuncture (BVA) for controlling of chronic low back pain (CLBP). We compared the effects of BVA on 40 patients with CLBP, pre-and post-treatment. The age of patient ranged from 38 to 65 with history of back pain more than 6 months. The curative effect was measured by scoring of visual analog scale (VAS), Oswestry Disability Index (ODI), serum levels TNFα, IL1β, IL-6, and NF-KB as well as ESR before and after BVA treatment. The obtained results revealed that the application of BVA ameliorated the disturbances induced by CLBP, as it showed a significant improvement in VAS (65%) accompanied with a significant improvement in ODI (75.6%) in all patients. Moreover, BVA treatment resulted in a significant (p < 0.05) amelioration in serum level of TNFα (-14%), IL1β (-52%), IL-6 (-53%) and NFKB (-32.6%) and ESR (-39.8%). From the mentioned findings, it could be concluded that BVA performed an improvement in CLBP patients, regarding pain intensity, disability and quality of life supported with improvement in serum levels of TNFα, IL1β, IL-6 and NF-κB and ESR.
... The patient was stung by three bees and one day after the bee stings, the patient's painful post-herpetic neuralgia was completely relieved, and the relief lasted for 1 and a half months. The researchers then suggested that BV therapy should be further investigated as a potential treatment modality for post-herpetic neuralgia [47]. ...
Article
Full-text available
The Honeybee (Apis mellifera) is one of the world’s most beneficial insects, as it plays a critical role in many terrestrial ecosystems. The use of honeybee products has been documented for thousands of years in many cultures for the treatment of human diseases, and their healing properties have been documented in many religious texts. The present study sets out to compile information on the history, chemical composition and scientific evidence concerning bee venom research. The promising bioactivities have the potential to provide practical directions for further investigation. PubMed database, Google Scholar Library, research articles, books, and relevant web pages have been accessed to accumulate data so that the updated information included in this study is as current as possible. At least 18 pharmacologically active components including various enzymes, peptides, and amines are present in bee venom. Medicinal use of bee venom therapy wields significant in vivo and in vitro outcomes to some extent mitigate the effects of Parkinson’s disease, Alzheimer’s disease, HIV, arthritis, liver fibrosis, cancer, tumors, fibrotic diseases, Lyme disease, etc. The effects of bee venom were the first documented in 1888 with the publication of a European clinical study conducted on its impact on rheumatism. According to a study published in the journal, bee venom has been used to treat various conditions for centuries. Such research activities confirm the therapeutic effectiveness of bee venom and as a potential future biomedicine.
... Honey bee sting treatment is progressively used to treat patients with various sclerosis (MS) in the conviction that it can settle or enhance the illness. A randomized traverse concentrate revealed that treatment with honey bee sting treatment in patients with backsliding different sclerosis did not decrease sickness action, inability, or exhaustion and did not improve these patients' personal satisfaction (Janik et al., 2007). ...
Article
The honeybee is the most beneficial insect in the World. It plays the major role in various kinds of terrestrial ecosystem. It is used for different sorts for the treatment of numerous human disease, and in the wound healing properties. We review on history, composition, and their biological activities. The major biological activities in the present review including the Cancer, fibrotic disease, liver fibrosis, HIV, Arthritis, Alzheimer’s disease, Parkinson’ s disease Lyme disease etc. The initial study of the bee venom were first time published in 1888 in European clinical study that were studied on the rheumatism. The previous studies showed that honeybee Venom used for the therapeutic effective and used for the future biomedicines.
... Honey bee sting treatment is progressively used to treat patients with various sclerosis (MS) in the conviction that it can settle or enhance the illness. A randomized traverse concentrate revealed that treatment with honey bee sting treatment in patients with backsliding different sclerosis did not decrease sickness action, inability, or exhaustion and did not improve these patients' personal satisfaction (Janik et al., 2007). ...
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Full-text available
The honeybee is the most beneficial insect in the World. It plays a major role in various kinds of the terrestrial ecosystem. It is used for different sorts for the treatment of numerous human disease and in the wound healing properties. We review on history, composition, and their biological activities. The major biological activities in the present review including the Cancer, fibrotic disease, liver fibrosis, HIV, Arthritis, Alzheimer's disease, Parkinson' s disease Lyme disease etc. The initial study of the bee venom was first time published in 1888 in European clinical study that was studied on rheumatism. The previous studies showed that honeybee Venom used for the therapeutic effects and used for future biomedicines.
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Background: No universal consensus about optimal modality for treating the recalcitrant localized plaque psoriasis (RLPP) is available. Objective: To evaluate the immunological and clinical therapeutic effect of using apitherapy in the treatment of RLPP. Methods: Randomized 50 patients with RLPP received apitherapy (n = 25) and placebo (n = 25) every week. Both treatments were injected into lesions at weekly intervals for a maximum of 12 treatments. Following up was 6 months later. Tumor necrosis factor-alpha (TNF-α) level was measured at pre-study and at 12th week. Results: A significant difference was found between the therapeutic responses of RLPP to the apitherapy and placebo groups (p<0.001). In the apitherapy group, complete response was achieved in 92% of patients. There was statistically significant decrease in TNF-α in the apitherapy group compared to the placebo group. No recurrence was observed in the apitherapy group. Conclusion: Apitherapy is effective and a safe treatment for recalcitrant localized plaque psoriasis, when other topical or physical therapies have failed.
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BACKGROUND: Temperature measurement of the knee joint has a long tradition in medical thermometry. However, neither a standard for recording knee temperature nor agreed values of knees in healthy subjects or in articular disease are available. AIM OF THE STUDY: To compute available data on knee temperature from the literature including the conditions of temperature recording, measurement sites and temperature values. METHOD: A literature search was performed in the databases Medline and Embase using the search terms “skin temperature“ or ”intra-articular temperature” and “knee”. Only papers written in English or German related to humans were considered for inclusion. The following data were extracted from included papers: Surface (skin) temperature, intra-articular temperature, site of measurement for skin or intra-articular temperature, measurement device, number of investigated knees, diagnosis of investigated subjects, biographic data of investigated subjects, room temperature, time of acclimatisation. If possible, temperature values were pooled if they have been recorded under similar conditions. RESULTS: In total, the database included temperature measurements from 3463 knee joints, comprising data from 876 healthy subjects, 629 patients with osteoarthritis (OA), 512 patients with rheumatoid arthritis (RA), 67 patients with non rheumatoid and other non specified inflammatory arthritis have been investigated. 86 patients suffered from joint inflammation caused by trauma, and 96 patients had various injuries of ligaments and other fibro-cartilagenous tissues of the knee. 131 temperature measurements were performed during surgery and 285 after surgery. 33 patients suffered from algodystrophy, 200 patients were investigated during or after various methods of cryotherapy and 50 subjects during heat treatment.Only pattern description without temperature values was reported in 5700 other subjects with various knee disorders.Based on contact temperature measurements, the mean temperature of the anterior knee in healthy subjects was 30.5 ± 1.1°C. Determined with radiometers, the corresponding mean temperature was 28.7 ± 0.6°C (95% confidence interval:27.9 to 29.5). In thermal images from healthy subjects, the mean temperature of the anterior knee was 29.5 ± 1.6°C (95%confidence interval: 28.5 to 30.5°C) and 33,1±0.0 °C of the posterior knee. The side difference of temperature was 0.2 ±1°C for both the anterior and the posterior knee. Mean intra-articular temperature varied between measurements recorded during knee surgery (29.9 ± 4.4 °C; 95% confidence interval: 23.0 to 36.8), in patients with rheumatoid arthritis (35,1 ± 0.7 °C; 95% confidence interval: 34.2 to 36.0°C) or osteoarthritis (33,5 2,7°C; 95% confidence interval: 30.1 to 36.9) and healthy subjects (32.6 ± 0.9°C; 95%confidence interval: 31.5 to 33.7). Measurements with contact thermometers revealed in patients with rheumatoid arthritis a mean temperature of 32.5 ±0.9°C (95% confidence interval: 31.4 to 33.9°C) for the anterior knee, while the corresponding temperature recorded with infrared thermal images was 30.5 ± 0.8°C (95% confidence interval: 27.8 to 33.1°C). In osteoarthritis patients, contact thermometers obtained a mean anterior knee temperature of 31.3 ± 1,3°C and temperature measurements from infrared thermograms revealed a mean temperature of 30.7 ± 1.3°C (95% confidence interval: 29.4 to 32.0 °C). CONCLUSION: Knee temperatures vary with respect to the method of temperature determination and between different health conditions of the knee joint. Moreover, mean knee temperature describes the condition of the knee incompletely and should be supplemented with a description of the temperature distribution.
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Bee venom (BV) has traditionally been used in Oriental medicine to relieve pain and to treat inflammatory diseases such as rheumatoid arthritis (RA). While several investigators have evaluated the anti-inflammatory effect of BV treatment, the anti-nociceptive effect of BV treatment on inflammatory pain has not been examined. Previous studies in experimental animals suggest that the therapeutic effect of BV on arthritis is dependent on the site of administration. Because of this potential site specificity, the present study was designed to evaluate the anti-nociceptive effect of BV injections into a specific acupoint (Zusanli) compared to a non-acupoint in an animal model of chronic arthritis. Subcutaneous BV treatment (1 mg/kg per day) was found to dramatically inhibit paw edema caused by Freund's adjuvant injection. Furthermore, BV therapy significantly reduced arthritis-induced nociceptive behaviors (i.e. the nociceptive scores for mechanical hyperalgesia and thermal hyperalgesia). These anti-nociceptive/anti-inflammatory effects of BV were observed from 12 days through 21 days post-BV treatment. In addition, BV treatment significantly suppressed adjuvant-induced Fos expression in the lumbar spinal cord at 3 weeks post-adjuvant injection. Finally, injection of BV into the Zusanli acupoint resulted in a significantly greater analgesic effect on arthritic pain as compared to BV injection in to a more distant non-acupoint. The present study demonstrates that BV injection into the Zusanli acupoint has both anti-inflammatory and anti-nociceptive effects on Freund's adjuvant-induced arthritis in rats. These findings raise the possibility that BV acupuncture may be a promising alternative medicine therapy for the long-term treatment of rheumatoid arthritis.
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Although the injection of bee venom (BV) has been reported to evoke tonic pain and hyperalgesia, there is conflicting evidence in the literature indicating that BV can also exert an anti-inflammatory and antinociceptive effects on inflammation. In this regard, BV has been traditionally used in Oriental medicine to relieve pain and to treat chronic inflammatory diseases such as rheumatoid arthritis. The present study was designed to test the hypothesis that BV induces acute nociception under normal conditions, but that it can serve as a potent anti-inflammatory and antinociceptive agent in a localized inflammatory state. The experiments were designed to evaluate the effect of BV pretreatment on carrageenan (CR)-induced acute paw edema and thermal hyperalgesia. In addition, spinal cord Fos expression induced by peripheral inflammation was quantitatively analyzed. In normal animals subcutaneous BV injection into the hindlimb was found to slightly increase Fos expression in the spinal cord without producing detectable nociceptive behaviors or hyperalgesia. In contrast pretreatment with BV (0.8 mg/kg) 30 min prior to CR injection suppressed both the paw edema and thermal hyperalgesia evoked by CR. In addition, there was a positive correlation between the percent change in paw volume and the expression of Fos positive neurons in the spinal cord. These results indicate that BV pretreatment has both antinociceptive and anti-inflammatory effects in CR-induced inflammatory pain. These data also suggest that BV administration may be useful in the treatment of the pain and edema associated with chronic inflammatory diseases.
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The goal of the present study was to determine whether bee venom (BV) injection into the Zhongwan acupoint (CV12), compared to injection into a non-acupoint, produced antinociception in an acetic acid-induced visceral pain model. This was accomplished by injecting BV subcutaneously into the Zhongwan acupoint or into a non-acupoint 30 min before intraperitoneal injection of acetic acid in ICR mice. BV injection into the acupoint produced a dose dependent suppression of acetic acid-induced abdominal stretches and of acetic acid-induced Fos expression in the spinal cord and the nucleus tractus solitarii. In contrast BV injection into the non-acupoint only produced antinociception at the highest dose of BV tested. Naloxone pretreatment did not alter the antinociceptive effect of BV acupoint injection on the abdominal stretch reflex. On the other hand, pretreatment with the alpha 2-adrenoceptor antagonist, yohimbine completely blocked the antinociceptive effect of BV acupoint injection. These results imply that BV acupoint stimulation can produce visceral antinociception that is associated with activation of alpha 2-adrenoceptors, but not with naloxone-sensitive opioid receptors.
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Unlabelled: Chemical acupuncture with diluted bee venom (DBV), termed apipuncture, has been traditionally used in oriental medicine to treat several inflammatory diseases and chronic pain conditions. In the present study we investigated the potential antihyperalgesic and antiallodynic effects of apipuncture in a rat neuropathic pain model. DBV (0.25 mg/kg, subcutaneous) was injected into the Zusanli acupoint 2 weeks after chronic constrictive injury (CCI) of the sciatic nerve. Between 5 and 45 minutes after DBV injection, we observed a significant reduction in the thermal hyperalgesia induced by CCI, but apipuncture failed to reduce CCI-induced mechanical allodynia. We subsequently examined whether this antihyperalgesic effect of apipuncture was related to the activation of spinal opioid receptors and/or alpha2-adrenoceptors. Intrathecal pretreatment with naloxone (10 microg/rat), an opioid receptor antagonist, did not reverse the antihyperalgesic effect of apipuncture, whereas pretreatment with idazoxan (40 microg/rat), an alpha2-adrenoceptor antagonist, completely blocked the effect of apipuncture. These results indicate that DBV-induced apipuncture significantly reduces the thermal hyperalgesia generated by CCI and also suggest that this antihyperalgesic effect is dependent on the activation of alpha2-adrenoceptors, but not opioid receptors, in the spinal cord. Perspective: The antinociceptive effect of apipuncture was evaluated in a rodent neuropathic pain model. The relieving effect of apipuncture on thermal hyperalgesia was found to be mediated by spinal alpha2-adrenoceptors, but not opioid receptors. These data suggest that apipuncture might be an effective alternative therapy for patients with painful peripheral neuropathy, especially for those who are poorly responsive to opioid analgesics.
Article
In a previous report, subcutaneous injection of diluted bee venom (dBV) into a specific acupuncture point (Zusanli, ST36), a procedure termed apipuncture, was shown to produce an antinociceptive effect in the rat formalin pain model. However, the central antinociceptive mechanisms responsible for this effect have not been established. Traditional acupuncture-induced antinociception is considered to be mediated by activation of the descending pain inhibitory system (DPIS) including initiation of its opioidergic, adrenergic and serotonergic components. The purpose of the present study was to investigate whether the antinociceptive effect of apipuncture is also mediated by the DPIS. Behavioral experiments verified that apipuncture significantly reduces licking behavior in the late phase of formalin test in rats. This antinociceptive effect of apipuncture was not modified by intrathecal pretreatment with naltrexone (a non-selective opioid receptor antagonist), prazosin (an alpha1 adrenoceptor antagonist) or propranolol (an beta adrenoceptor antagonist). In contrast, intrathecally injected idazoxan (an alpha2 adrenoceptor antagonist) or intrathecal methysergide (a serotonin receptor antagonist) significantly reversed apipuncture-induced antinociception. These results suggest that apipuncture-induced antinociception is produced by activation of alpha2 adrenergic and serotonergic components of the DPIS.
Article
We have previously shown that subcutaneous bee venom (BV) injection reduces visceral pain behavior in mice, but it is not clear which constituent of BV is responsible for its antinociceptive effect. In the present study, we now demonstrate that a water-soluble subfraction of BV (BVA) reproduces the antinociceptive effect of BV in acetic acid-induced visceral pain model. We further evaluated three different BVA subfractions that were separated by molecular weight, and found that only the BVAF3 subfraction (a molecular weight of <10 kDa) produced a significant antinociceptive effect on abdominal stretches and suppressed visceral pain-induced spinal cord Fos expression. Injection of melittin (MEL), a major constituent of BVAF3, also produced a visceral antinociception. However, melittin's antinociception was completely blocked by boiling for 10 min at 100 degrees C, while boiling either whole BV or BVAF3 did not prevent their antinociception. The antinociceptive effect of BVAF3 was completely blocked by intrathecal pretreatment with the alpha2-adrenoceptor antagonist, yohimbine (YOH), while intrathecal pretreatment with the opioid antagonist, naloxone (NAL) or the serotonin antagonist, methysergide, had no effect. These data demonstrate that BVAF3 is responsible for the visceral antinociception of whole BV and further suggest that this effect is mediated in part by spinal alpha2-adrenergic activity.
Article
Several lines of evidence indicate significant interactions between the immune and nervous systems. Our recent study reveals that 'bee venom (BV) induced anti-inflammatory effect' (BVAI) was produced by sympathetic preganglionic neuronal activation and subsequent adrenomedullary catecholamine release in a zymosan-induced inflammation model. However, the specific peripheral input and the supraspinal neuronal systems that are involved in this BVAI remain to be defined. Here we show that subcutaneous BV injection into left hind limb significantly reduces zymosan-induced leukocyte migration and that this effect is completely inhibited by denervation of the left sciatic nerve. This BVAI was not affected by the destruction of capsaicin-sensitive primary afferent fibers using either neonatal capsaicin or resiniferatoxin (RTX) pretreatment. BV injection into the left hind limb significantly increased Fos expression in the contralateral locus coeruleus (LC) in non-inflamed mice. In zymosan-inflamed mice, BV injection produced a further increase in LC Fos expression as compared with non-inflamed mice. This BV-induced Fos increase in the LC was not affected by RTX pretreatment. Pharmacological blockage of central noradrenergic activity by either central chemical sympathectomy (i.c.v. 6-hydroxydopamine) or alpha2 adrenoceptor antagonism (i.c.v. idazoxan) completely blocked BVAI. Taken together, these results suggest that BVAI is mediated by peripheral activation of capsaicin-insensitive primary afferent fibers and subsequent central noradrenergic activation including the LC.
Article
Bee venom is used as a traditional medicine for treatment of arthritis. The anti-inflammatory activity of the n-hexane, ethyl acetate, and aqueous partitions from bee venom (Apis mellifera) was studied using cyclooxygenase (COX) activity and pro-inflammatory cytokines (TNF-alpha and IL-1beta) production, in vitro. COX-2 is involved in the production of prostaglandins that mediate pain and support the inflammatory process. The aqueous partition of bee venom showed strong dose-dependent inhibitory effects on COX-2 activity (IC50 = 13.1 microg/mL), but did not inhibit COX-1 activity. The aqueous partition was subfractionated into three parts by molecular weight differences, namely, B-F1 (above 20 KDa), B-F2 (between 10 KDa and 20 KDa) and B-F3 (below 10 KDa). B-F2 and B-F3 strongly inhibited COX-2 activity and COX-2 mRNA expression in a dose-dependent manner, without revealing cytotoxic effects. TNF-alpha and IL-1beta, are potent pro-inflammatory cytokines and are early indicators of the inflammatory process. We also investigated the effects of three subfractions on TNF-alpha and IL-1beta production using ELISA method. All three subfractions, B-F1, B-F2 and B-F3, inhibited TNF-alpha and IL-1beta production. These results suggest the pharmacological activities of bee venom on anti-inflammatory process include the inhibition of COX-2 expression and the blocking of pro-inflammatory cytokines (TNF-alpha, and IL-1beta) production.
Article
Unlabelled: Peripheral bee venom (BV) administration produces 2 contrasting effects, nociception and antinociception. This study was designed to evaluate whether the initial nociceptive effect induced by BV injection into the Zusanli acupoint is involved in producing the more prolonged antinociceptive effect observed in the mouse formalin test, and whether capsaicin-sensitive primary afferents are involved in these effects. BV injection into the Zusanli point increased spinal Fos expression but not spontaneous nociceptive behavior. BV pretreatment 10 minutes before intraplantar formalin injection dose-dependently attenuated nociceptive behavior associated with the second phase of the formalin test. The destruction of capsaicin-sensitive primary afferents by resiniferatoxin (RTX) pretreatment selectively decreased BV-induced spinal Fos expression but did not affect BV-induced antinociception. Furthermore, BV injection increased Fos expression in tyrosine hydroxylase immunoreactive neurons in the locus caeruleus, and this expression was unaltered by RTX pretreatment. Finally, BV's antinociception was blocked by intrathecal injection of 10 microg idazoxan, and this effect was not modified by RTX pretreatment. These findings suggest that subcutaneous BV stimulation of the Zusanli point activates central catecholaminergic neurons via capsaicin-insensitive afferent fibers without induction of nociceptive behavior. This in turn leads to the activation of spinal alpha2-adrenoceptors, which ultimately reduces formalin-evoked nociceptive behaviors. Perspective: This study demonstrates that BV acupuncture produces a significant antinociception without nociceptive behavior in rodents, which is mediated by capsaicin-insensitive afferents and involves activation of central adrenergic circuits. These results further suggest that BV stimulation into this acupuncture point might be a valuable alternative to traditional electrical or mechanical acupoint stimulation.