American Journal of Chinese Medicine

A Comparative Study with Needle Acupuncture

The Analgesic Efficacy of Bee Venom Acupuncture for Knee Osteoarthritis: A Comparative Study with Needle Acupuncture

Young-Bae Kwon

Abstract: The aim of this investigation was to determine whether bee venom (BV) administered directly into an acupoint was a clinically effective and safe method for relieving the pain of patients with knee osteoarthritis (OA) as compared to traditional needle acupuncture. We evaluated the efficacy of BV acupuncture using both pain relief scores and computerized infrared thermography (IRT) following 4 weeks of BV acupuncture treatment. We observed that a significantly higher proportion of subjects receiving BV acupuncture reported substantial pain relief as compared with those receiving traditional needle acupuncture therapy. Furthermore, the IRT score was significantly improved and paralleled the level of pain relief.

Osteoarthritis (OA) is characterized by degeneration of articular cartilage with proliferation and remodeling of subchondral bone. The knee joint is one of the more commonly afflicted joints. The usual symptoms of OA are stiffness, limitation of motion and pain. Clinically, patients with OA of the knee have pain in and around the knee joint that is typically worse with weight beating and improved with rest or suitable exercise.

Patients with OA receive many medically prescribed drugs and often require extensive hospital and surgical management. The pharmacologic therapy for relieving pain and other symptoms in patients with OA of the knee consists of several regimens including intra-articular steroid injections, non-opioid analgesics (i.e., acetaminophen), topical analgesics (i.e., capsaicin) and nonsteroidal anti-inflammatory drugs (NSAIDs) (Hochberg et al., 1995). While these medications often relieve symptoms associated with OA, they are far from ideal therapeutic agents. NSAIDs, in particular, can cause serious side effects, including peptic ulcer and hepatic or renal failure. Unfortunately none of these classes of medications can prevent or delay the progression of OA (Gaby, 1999). On the contrary, there is evidence, both in animals with experimental OA and in humans, that administration of NSAIDs may actually accelerate joint destruction (Brandt, 1987; Rashad et al., 1989). Because of these shortcomings, a more effective and safer therapeutic strategy is desired to treat OA.

As an alternative to drug administration, a variety of treatments have been developed to manage pain in OA (Perrot and Menkes, 1996). In many Asian countries and increasingly in Western countries, acupuncture is one of the most frequently used techniques for OA (Thomas et al., 1991; Robin and Joan, 1998). In recent years, there have been increasing numbers of studies that have attempted to reexamine traditional acupuncture within the framework of Western scientific medicine. Currently, it is thought that acupuncture modulates pain transmission and pain responses by activation of the endogenous antinociceptive system (Ulett et al., 1998). Thus, the most common use of acupuncture is for the treatment of pain, typically for chronic or post-surgical pain (Lewith and Machin, 1983; Robin and Joan, 1998). In OA patients, acupuncture is the most frequently used complementary therapy, and its therapeutic efficacy and safety have been addressed in several clinical trials (Thomas et al., 1991; Christensen et al., 1992; Berman et al., 1999).

It has been postulated that there are marked variations in the analgesic effect of acupuncture according to the acupuncture point stimulated and the type of needle manipulation used (Kudriavtsev and Vlasik, 1994; Guo et al., 1996; Farber et al., 1997; Kim et al., 2000). In addition to the traditional method of manual manipulation with an acupuncture needle, a number of other treatment variations have been developed which include acupressure, moxibustion and neuroelectric stimulation of the acupoint (McLellan et al., 1993). Another less well-known method of stimulating an acupoint is to directly inject bee venom (BV) into it. It is important to note that bee sting therapy has been utilized for a long time in oriental medicine as a traditional medical approach to relieve pain and to cure inflammatory diseases in humans (Billingham et al., 1973). Moreover, BV acupuncture has been used more recently as an alternative method of acupuncture. Unfortunately there have been no studies that have examined the effectiveness of BV acupuncture in comparison to traditional needle acupuncture. In the present study, we determined if stimulation caused by BV acupuncture led to analgesia in OA patients and compared the effectiveness of BV acupuncture to the more traditional needle acupuncture in producing pain relief.

The aims of this investigation were to determine whether BV acupuncture is a clinically effective and safe method for relieving pain in patients with knee OA and to compare the therapeutic effect of BV acupuncture to traditional needle acupuncture. We also evaluated the efficacy of BV acupuncture on knee temperature using computerized infrared thermography (IRT) as previously described (Thomas et al., 1990).

Materials and Methods


The study protocol adhered to the ethical guidelines of the International Association for the Study of Pain, it was approved by our institutional ethical committee and written informed consent was obtained from each patient. Data were obtained from the Department of Acupuncture and Moxibustion at the Kyung-hee Oriental Medical Center (Seoul, Korea) during the period between October 1998 and May 1999. This clinical trial consisted of 60 outpatients (50 women, 10 men; mean year: 52.6 [+ or -] 14.3) diagnosed as having OA of the knee, based on radiological and clinical findings. Patients were considered eligible for treatment if they currently were not being treated for a chronic or terminal illness and had a radiological score of 2 or greater using the Kellgren-Lawrence scale. Before the clinical trial began, patients were classified using the following clinical criteria:

Disease Duration

1) Acute stage: onset of pain within the last month

2) Subacute stage: onset of pain within the previous 2-5 months

3) Chronic stage: pain of at least 6 month’s duration

Disease Type

1) Unilateral knee pain: left or right

2) Bilateral knee pain

Radiological Grade

Knee radiographs were given scores for global severity of OA (Kellgren-Lawrence scale: range 0 to 4).

At the conclusion of the clinical trials the therapeutic efficacy of BV acupuncture in each of the above clinical states was evaluated.

Therapeutic Methods

Sixty patients with OA of the knee were randomly assigned to a needle acupuncture (n=20) or BV acupuncture (n=40) group. Selection of acupuncture points was based on the Traditional Chinese Medicine (TCM) theory for treating Bi syndrome, which uses local and distal points on channels that traverse the area of pain (Berman et al., 1999). The selection of specific acupoints for each patient was based on individual pain symptoms and was selected out of a list of seven acupoints (or a total of 14 points bilaterally, Table 1). Each patient received stimulation of multiple acupoints at each treatment session, but the total number of acupoints stimulated did not exceed 5 unilaterally (or 10 points bilaterally). Either needle acupuncture or BV acupuncture was applied twice a week and continued for 4 weeks. In the needle acupuncture treatment group, stainless steel needles (0.25 x 30 mm) were inserted to a depth of 10-30 mm depending upon the specific acupoint for 20 min. The De Qi sensation (the characteristic acupuncture effect of needle-manipulation sensation) was verified by the patient. In the BV acupuncture treatment group, BV (Sigma Chemical, St. Louis, MO, USA, Cat #: V3125) was dissolved in saline (diluted to 0.03%) and intradermally administered into the specific acupoints. A volume of 0.1 ml of BV was injected into each acupoint and the total injected volume/patient did not exceed 1 ml as similar manner with needle acupuncture.

Table 1. Anatomical Location of Acupoint Used for Treatment

Acupuncture point Anatomical location

Xuehai (SP10) Located on the anterior medial surface of the

thigh, 6 cm above the articular flexure of the


Liangqiu (ST34) Located 6 cm above the lateral upper border of

the patella on the anterior surface of the thigh,

at the border of rectus femoris

Zusanli (ST36) Located on the anterior surface of the leg, 3 cm

lateral to the lateral border of the tibia, 9 cm

below the patella

Yanglingquan (GB34) Located on the lateral surface of the leg below

the head of the fibula, 3 cm below the knee

between the tibia and fibula

Taichong (LR3) Located on the dorsal surface of the foot, at the

angle between the 1st and the 2nd toe metatarsal


Haoding (Ex-LE2) Located at the center of the patella

Xiyen (Ex-LE5) Located at the knee joint, in both hollows

between the femur and the tibia, medial & lateral

to the patellar when the knee is bent

Meridian abbreviations is based on Standard Acupuncture Nomenclature

published the WHO, 1991.

Outcome Measures

Subjective Pain Relief Score

At the end of the therapeutic period, patients were asked to evaluate the therapeutic efficacy of the acupuncture treatment on the reduction of OA-induced pain. For the present study, the pain relief score was determined based on four subjective grades. The patients were asked to characterize the effectiveness of their treatment into one of four categories (excellent, good, fair and poor; taking into account the amount of pain relief they received, the amount of joint stiffness that remained and the return of joint flexibility). These verbal grades were converted into a numerical score (1-4) and recorded. This method did not include a large number of formal questions related to OA pain such as those included in the WOMAC index (Roos et al., 1999). The Western Ontario and MacMaster Universities (WOMAC) Osteoarthritis Index is a widely used self-administered health status measure assessing pain, stiffness, and function in patients with OA of the hip or knee (Bellamy et al., 1988). To enable comparison between assessments made in different countries, these measures need not only be translated, but also adapted for use in different cultures. In the context of the present study the linguistic translation of the WOMAC index and the cultural differences associated with the Korean society made it difficult to apply the WOMAC index. Instead of using the WOMAC index, a simplified scoring index was designed that did take into consideration pain, stiffness and joint function. Patients were thus asked to rate the effect of the acupuncture treatment on pain, stiffness and joint function. These scores were averaged to come up with an overall therapeutic efficacy score. Overall therapeutic efficacy scores of 1-4 were assigned based on the following criteria:

Excellent (score: 4): OA symptoms completely disappeared after therapy

Good (score: 3): OA symptoms were significantly improved after therapy

Fair (score: 2): OA symptoms were slightly improved after therapy

Poor (score: 1): OA symptoms were not improved after therapy

Infrared Thermography

Only twenty-six of the 40 BV acupuncture treated patients agreed to IRT analysis, so thermography was performed on these 26 patients. Before and 4 weeks after BV acupuncture therapy was initiated thermographic assessments were performed with an infrared thermography (IRT) system (Dorex Inc., Orange, CA, USA) using computer assisted thermographic software and an IBM PXT for digitization of signals, storage and analysis of data. All patients followed a strict preparation protocol prior to IRT that involved fasting for 3 hr with no analgesics, smoking, exercises or acupuncture on the morning of the test. Subjects were seated with their upper and lower limbs exposed and equilibration was allowed to occur in a thermostatic room (19-20 [degrees] C) for 20 min prior to IRT assessment. Thermographic assessment was performed in both the anterior and posterior areas of the knee joint. When the computer based side-to-side (left-to-right) leg temperature difference ([Delta]T) was greater than 0.5 [degrees] C, this was also considered to be abnormal in unilateral OA patients. Because asymmetry and disruption of thermal concentric circle (e.g., a general increase centrally over the marginal area) as well as higher temperature in knee joint as compared with upper thigh was observed in bilateral OA patients, this abnormality was also included as indicator of pain. Finally, the change in [Delta]T was evaluated alone and this data was then combined with the degree of asymmetry in the thermal concentric circle data. The combined IRT data obtained from each patient before BV acupuncture was compared with that obtained following BV treatment to come up with an IRT based grade as follows:

Excellent: [Delta]T was decreased to 0.5 [degrees] C or less after BV acupuncture and the thermal concentric circle was in the normal range.

Good: [Delta]T was decreased after BV acupuncture, but [Delta]T was still greater than 0.5 [degrees] C and the asymmetry of the thermal concentric circle improved significantly but some abnormalities were still evident.

Fair: [Delta]T and the asymmetry of the thermal concentric circle did not change after BV acupuncture, but remained at the pre-acupuncture state

Poor: [Delta]T and the asymmetry of the thermal concentric circle both increased after BV acupuncture

Statistical Analysis

The subjective pain relief scores and IRT scores were expressed as the mean [+ or -] SD. Significant differences in the pain relief scores between the needle acupuncture and BV acupuncture groups were evaluated by Student’s t-test. Throughout, p [is less than] 0.05 was considered to be statistically significant.


Overall Assessment of the Effect of Needle Versus BV Acupuncture

Both BV acupuncture and needle acupuncture were found to have therapeutic efficacy in OA patients (Table 2). Interestingly, the majority of the BV acupuncture group rated the therapeutic efficacy of their treatment as “excellent (37.5%) or good (45%),” whereas the majority of the needle acupuncture group rated the therapeutic efficacy of their treatment as “good (50%) or fair (40%)” (Table 2). The mean therapeutic efficacy score was significantly different between the needle acupuncture group and BV acupuncture group (2.55 [+ or -] 0.67 and 3.20 [+ or -] 0.72, respectively, P [is less than] 0.01). These data indicate that the BV acupuncture treatment provided more effective therapeutic pain relief than did traditional needle acupuncture therapy in this clinical trial.

Table 2. Assessment of the Therapeutic Efficacy after

Acupuncture and Bee Venom (BV) Acupuncture

Assessment of BV

The therapeutic Acupuncture group (n=20) acupuncture group (n=40)

efficacy No. of subjects (%) No. of subjects (%)

Excellent 1 (5.0) 15 (37.5)

Good 10 (50.0) 18 (45.0)

Fair 8 (40.0) 7 (17.5)

Poor 1 (5.0) 0 (0)

Therapeutic Efficacy Versus Disease Duration

When therapeutic efficacy was evaluated according to the duration of the disease, needle acupuncture and BV acupuncture both showed valuable therapeutic effects depending on the duration of the OA (Table 3). In this study, the majority of patients (about 60%) had experienced pain for a duration of at least 6 months, which was categorized as chronic stage OA. In these patients, the therapeutic efficacy score of needle acupuncture and BV acupuncture were 2.64 [+ or -] 0.80 and 3.15 [+ or -] 0.78, respectively, suggesting that both types of acupuncture treatment increased pain relief. Interestingly, the only statistically significant difference in the therapeutic efficacy scores between the needle acupuncture and BV acupuncture groups occurred in the subacute stage of OA (2.40 [+ or -] 0.55 and 3.25 [+ or -] 0.46, respectively, P [is less than] 0.05, Table 3).

Table 3. The Therapeutic Efficacy of Needle Acupuncture and Bee

Venom (BV) Acupuncture with Respect to the Duration of the Patients’


Needle Acupuncture BV acupuncture

group (n=20) group (u=40)

Disease No. of Efficacy No. of Efficacy

Duration subjects score subjects score

(%) (%)

2.50 3.33

Acute stage 4 (20.0) [+ or -] 6 (15.0) [+ or -]

(<1 month) 0.58 0.82

2.40 3.25

Subacute stage 5 (25.0) [+ or -] 8 (20.0) [+ or -]

(1-5 months) 0.55 0.46(*)

2.64 3.15

Chronic stage 11 (55.0) [+ or -] 26 (65.0) [+ or -]

(>6 months) 0.80 0.78

(*) p<0.05: statistical difference between acupuncture group and

BV acupuncture group

Therapeutic Efficacy Versus the Laterality of the OA Lesion

With respect to OA involvement of one or both limbs, there was no difference in the therapeutic efficacy score between unilateral lesions and bilateral lesions in either the BV acupuncture or the needle acupuncture groups (Table 4). BV acupuncture produced a statistically, significantly higher therapeutic efficacy score than traditional acupuncture therapy in patients with unilateral OA lesions (P [is less than] 0.01, Table 4).

Table 4. The Therapeutic Efficacy after Acupuncture and

Bee Venom (BV) Acupuncture According to OA Pain Distribution

(Disease Type)

Acupuncture group BV acupuncture

(n=20) group (n=40)

No. of Efficacy No. of Efficacy

Disease Lesion subjects score subjects score

(%) (%)

2.57 3.35

Unilateral 14 (70.0) [+ or -] 17 (42.5) [+ or -]

0.65 0.70(**)

2.50 3.08

Bilateral 6 (30.0) [+ or -] 23 (57.5) [+ or -]

0.84 0.73

(**) p<0.01: statistical difference between acupuncture group and BV

acupuncture group

Therapeutic Efficacy Versus the Radiological Grade of OA

In general, it has been reported that the radiological severity of OA does not correlate with the intensity of pain symptoms. Although we also observed this phenomenon, we evaluated the therapeutic efficacy of BV acupuncture based on the Kellgren-Lawrence radiological grade. It is notable that the radiographic grade of most patients (at least 50%) was classified as grade 3, and that BV acupuncture produced a significantly higher therapeutic efficacy score than needle acupuncture in these patients (Table 5, P [is less than] 0.01).

Table 5. The Therapeutic Efficacy after Acupuncture and Bee Venom (BV)

Acupuncture According to Subjective Radiological Grades (Kellgren and

Lawrence grade)

Acupuncture BV acupuncture

group (n=20) group (n=40)

Radiological No. of Efficacy No. of Efficacy

Classification subjects score subjects score

(%) (%)

2.67 3.38

Grade 2 3 (15.0) [+ or -] 8 (20.0) [+ or -]

0.58 0.74

2.54 3.24

Grade 3 16 (65.0) [+ or -] 21 (52.5) [+ or -]

0.66 0.70(**)

2.50 3.00

Grade 4 4 (20.0) [+ or -] 11 (27.5) [+ or -]

1.00 0.77

(**) p<0.01: statistical difference between acupuncture group and BV

acupuncture group

The Infrared Thermograph (IRT) for the Therapeutic Efficacy of BV Acupuncture

Prior to BV acupuncture treatment all 26 patients showed abnormalities in the IRT of the anterior area of the knee, but only 17 patients showed abnormalities in the posterior knee area thermographs. Four weeks after BV acupuncture therapy was initiated, the potential therapeutic efficacy of the BV acupuncture treatment was assessed by comparing the IRT of the anterior and posterior areas of knee to that obtained prior to treatment. Before BV acupuncture treatment, the temperature difference ([Delta]T) between the left and right knees was 0.60 [+ or -] 0.29 [degrees] C (i.e., abnormal) in the anterior area of the knee in all 26 patients (Figure 1A). However, after BV acupuncture therapy this temperature difference of the anterior knee area was normalized to 0.37 [+ or -] 0.18 [degrees] C (Figure 1B). In addition, the asymmetric thermal flare observed in the anterior knee area prior to treatment was significantly reduced by BV acupuncture in 15 of the 26 cases. The [Delta]T of the posterior knee area was reduced from 0.42 [+ or -] 0.20 [degrees] C to 0.29 [+ or -] 0.13 [degrees] C following BV acupuncture therapy. The change of [Delta]T and the asymmetry of the thermal concentric circle in the anterior and posterior knee areas were analyzed and scored before and after BV acupuncture based on the four categories listed in the methods section. We found that the thermographs of the anterior knee of 18/26 patients (70%) and the posterior knee of 10/17 patients (60%) had returned to normal (excellent grade, see Table 6) following BV treatment.

Table 6. The Assessment of Therapeutic Efficacy after

Bee Venom (BV) Acupuncture by Computerized Infrared Thermography

Assessment of Anterior area Posterior area

The therapeutic efficacy No. of subjects (%) No. of subjects (%)

Excellent 18 (69.3) 10 (58.8)

Good 5 (19.2) 5 (29.4)

Fair 3 (11.5) 2 (11.8)

Poor 0 (0) 0 (0)


Pain is considered by both patients and doctors to be the most important symptom to treat in cases of OA. In individuals with mild symptomatic OA, treatment may be limited to patient education, physical and occupational therapy and other non-pharmacologic modalities, or to pharmacologic therapy including non-opioid oral and topical analgesics. In patients who are unresponsive to these treatment regimens, the use of NSAIDs in addition to non-pharmacologic therapy is appropriate unless medically contraindicated (Hochberg et al., 1995). However, it has been previously reported that NSAIDs may be contraindicated in the management of OA because they are potent inhibitors of prostaglandin synthesis and reduction of vasodilator prostaglandin synthesis diminishes joint perfusion (Rashad et al., 1989). Clearly better therapeutic procedures for the management of OA pain and dysfunction are required.

Previous studies have established the effectiveness of acupuncture treatment in relieving both the pain and dysfunction of the knee in elderly patients with OA in comparison to non-acupuncture treated control groups (Thomas et al., 1991; Christensen et al., 1992; Berman et al., 1999). However, there have been no previous studies comparing traditional needle acupuncture with BV acupuncture. In the present study we evaluated the therapeutic efficacy and safety of BV acupuncture and compared it with that of traditional acupuncture treatment. Our results indicate that patients with OA of the knee showed significant improvement after 4 weeks of either needle or BV acupuncture therapy. Although our selection of acupoints is slightly modified from those used by Berman in a previously reported clinical trial (Berman et al., 1999), the overall therapeutic efficacy of needle acupuncture was similar between both studies. However, based on the therapeutical efficacy scores of needle acupuncture compared to BV acupuncture, we demonstrate in the present study that a majority (82.5%) of subjects receiving BV acupuncture (33 out of 40 subjects) reported substantial pain relief as compared with traditional acupuncture therapy (55%; Table 2). This improved pain relief score was produced by a 4 week course of BV acupuncture delivered twice a week. Furthermore, the therapeutical efficacy was favorable irrespective of disease duration (acute, subacute or chronic stage), arthritic type (unilateral or bilateral knee OA) and radiological severity.

In this study, the pain relief score was determined based on four subjective grades. As indicated in the methods section the linguistic translation of the WOMAC index and the cultural differences associated with the Korean society made it difficult to apply the WOMAC index in the context of the present study.

So rather than using this index, a simplified scoring index was designed as described in the methods. The therapeutic efficacy score obtained using this scoring method was confirmed using a more objective infrared thermography scoring system (see Table 6). IRT measures local skin temperature and therefore provides physiological data mediated through sympathetic nerve fibers. In arthritic patients, IRT has been shown to be a reproducible, sensitive, quantifiable method for measuring disease activity, and not subject to circadian variation or inter-observer error (Devereaux et al., 1985). In this regard Thomas and his colleagues (1990) have reported that an excellent correlation exists between IRT and magnetic resonance imaging (MRI, 94%), but also between IRT and computerized tomography (CT, 87%) and with myelography (94%) in patients with low back pain. Furthermore, these investigators suggest that IRT is a more sensitive method than MRI, CT and myelography for detecting abnormalities caused by pain (Thomas et al., 1990). The present study demonstrated a positive correlation between the IRT score and pain relief score (Table 6). Thus, the simplified four grade scoring method used in the present study was considered to be a condensed but reliable measurement of therapeutical efficacy in OA patients.

Although recent studies have demonstrated that BV injection evokes persistent pain and hyperalgesia (Lariviere and Melzack, 1996; Chen et al., 1999). BV has traditionally been used in Oriental medicine to relieve pain and to treat chronic inflammatory diseases such as rheumatoid arthritis (Eiseman et al., 1982; Somerfield and Brandwein, 1988). The anti-nociceptive effect of whole BV can be partially reproduced by some of its individual components, such as MCD peptide and adolapin (Martin and Hartter, 1980; Shkenderov and Koburova, 1982; Koburova et al., 1985). On the other hand, it has also been reported that unilateral subcutaneous injection of BV into the plantar surface of the hind paw produces tonic behavioral responses that are similar to those observed following capsaicin injection (Lariviere and Melzack, 1996; Chen et al., 1999). Moreover BV injection induces a pronounced primary hyperalgesia to mechanical and thermal stimuli in ipsilateral hindpaw and thermal hyperalgesia in the contralateral hindpaw (Chen et al., 1999). Chen and his colleagues (1998) previously reported that blockage of the sciatic nerve with lidocaine resulted in a complete suppression of the BV-induced neuronal firing in the spinal dorsal horn, suggesting that the central neuronal changes observed following subcutaneous BV injection are peripherally-mediated. In their recent study, it was also demonstrated that activation of protein kinase C in the spinal cord contributed to the induction and maintenance of both peripheral dependent pain and contralateral heat hyperalgesia which was depending upon central sensitization (Li et al., 2000).

While we know that BV is capable of producing activation of spinal neurons and central sensitization, it is not clear how BV injection into acupoints is able to suppress OA pain. The antinociceptive effects of BV may be explained by the process of counter-irritation; that is, when noxious stimuli are applied to body regions, these stimuli increase the pain thresholds and reduce pain rating scores throughout the body. For centuries, pain has been relieved by counter-irritation methods, including moxibustion (burning herbs to stimulate acupuncture points) on an arthritic limb or cauterizing above the hip for sciatica (Wand-Tetley, 1956). In addition, capsaicin, an extract of red, hot chili peppers now known to stimulate vanilloid receptors, produces itching, pricking and burning sensations caused by the excitation of nociceptors. Since repeated application of capsaicin is followed by a prolonged period of hypalgesia, usually referred to as desensitization or nociceptor inactivation, it has been traditionally used to treat certain types of pain (Fusco and Giacovazzo, 1997; Nolano et al., 1999). It has been reported that unilateral subcutaneous injection of BV into the plantar surface of the hind paw prolongs tonic behavioral responses similar to that of capsaicin (Lariviere and Melzack, 1996; Chen et al., 1999) and induces Fos expression in the ipsilateral dorsal horn of the spinal cord (Luo et al., 1998). Thus the long term stimulation caused by BV administration may eventually lead to nociceptor inactivation or analgesia similar to that reported for capsaicin. Although it remains to be determined whether peripherally administered BV activates endogenous antinociceptive pathways, it is possible that the antinociceptive effect of BV is partially mediated by peripheral counter-irritation.

In this clinical trial, we administered BV into several acupoints around the knee joint (Table 1). Selection of acupoints was based on the traditional Chinese medicine theory for treating Bi syndrome (Kudriavtsev and Vlasik, 1994; Cai, 1995), which uses local and distal points on channels that transverse the area of pain. BV injection into these acupoints evoked relief of OA induced pain, stiffness and flexibility. BV acupuncture was found to have improved therapeutic efficacy as compared to traditional needle acupuncture. These findings raise the possibility that BV acupuncture may be a promising alternative acupuncture therapy for OA.


This study was supported by grants from the 1999 Oriental Medicine 2010 R & D project (HMP-99-O-01-0001) from the Korean Ministry of Health and Welfare. The publication of this manuscript was also supported by the Brain Korea 21 project.


[1.] Bellamy, N., W.W. Buchanan, C.H. Goldsmith, J. Campbell and L.W. Stitt. Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. J. Rheumatol. 15: 1833-1840, 1988.

[2.] Berman, B.M., B.B. Singh, L. Lao, P. Langenberg, H. Li, V. Hadhazy, J. Bareta and M. Hochberg. A randomized trial of acupuncture as an adjunctive therapy in osteoarthritis of the knee. Rheumatology 38: 346-354, 1999.

[3.] Billingham, M.E., J. Morley, J.M. Hanson, R.A. Shipolini and C.A. Vernon. An anti-inflammatory peptide from bee venom. Nature 245: 163-164, 1973.

[4.] Brandt, K.D. Effects of nonsteroidal anti-inflammatory drugs on chondrocyte metabolism in vitro and in vivo. Am. J. Med. 83: 29-34, 1987.

[5.] Cai, W. Acupuncture and the nervous system. Am. J. Chin. Med. 20: 331-337, 1995.

[6.] Chen, J., C. Luo and H.L. Li. The contribution of spinal neuronal changes to development of prolonged, tonic nociceptive responses of the cat induced by subcutaneous bee venom injection. Eur. J. Pain 2: 359-376, 1998.

[7.] Chen, J., C. Luo, H, Li and H. Chen. Primary hyperalgesia to mechanical and heat stimuli following subcutaneous bee venom injection into the plantar surface of hindpaw in the conscious rat: a comparative study with the formalin test. Pain 83: 67-76, 1999.

[8.] Christensen, B.V., I.U. Iuhl, H. Vilbek, H.H. Bulow, N.C. Dreijer and H.F. Rasmussen. Acupuncture treatment of severe knee osteoarthrosis. A long-term study. Acta. Anaesthesiol. Scand. 36: 519-525, 1992.

[9.] Devereaux, M.D., G.R. Parr, D.P. Thomas and B.L. Hazleman. Disease activity indexes in rheumatoid arthritis; a prospective, comparative study with thermography. Ann. Rheum. Dis. 44: 434-437, 1985.

[10.] Eiseman, J.L., J. von Bredow and A.P. Alvares. Effect of honeybee (Apis mellifera) venom on the course of adjuvant-induced arthritis and depression of drug metabolism in the rat. Biochem. Pharmacol. 31:1139-1146, 1982.

[11.] Farber, P.L., A. Tachibana and H.M. Campiglia. Increased pain threshold following electroacupuncture: analgesia is induced mainly in meridian acupuncture points. Acupunct. Electrother. Res. 22: 109-117, 1997.

[12.] Fusco B.M. and M. Giacovazzo. Peppers and pain. The promise of capsaicin. Drugs 53: 909-914, 1997.

[13.] Gaby, A.R. Natural treatments for osteoarthritis. Altern. Med. Rev. 4: 330-341, 1999.

[14.] Guo, D., X. Guan and C. Wang. Segmental influence of dorsal root action potentials evoked by stimulating the acupoints after acupuncture along meridians. Chen. Tzu. Yen. Chiu. 21: 52-56, 1996.

[15.] Hochberg, M.C., R.D. Altman, K.D. Brandt, B.M. Clark, P.A. Dieppe, M.R. Griffin, R.W. Moskowitz and T.J. Schnitzer. Guidelines for the medical management of osteoarthritis. Part II. Osteoarthritis of the knee. American College of Rheumatology. Arthritis. Rheum. 38: 1541-1546, 1995.

[16.] Kim, J.H., B.I. Min, D. Schmidt, H.J. Lee and D.S. Park. The difference between electroacupuncture only and electroacupuncture with manipulation on analgesia in rats. Neurosci. Lett. 279: 149-152, 2000.

[17.] Koburova, K.L., S.G. Michailova and S.V. Shkenderov. Further investigation on the antiinflammatory properties of adolapin–bee venom polypeptide. Acta. Physiol. Pharmacol. Bulg. 11: 50-55, 1985.

[18.] Kudriavtsev, A. and T. Vlasik. Gentle and strong acupuncture: a short review of the two main approaches to treatment. Am. J. Chin. Med. 22:221-233, 1994.

[19.] Lariviere, W.R. and R. Melzack. The bee venom test: a new tonic-pain test. Pain 66: 271-277, 1996.

[20.] Lewith, G.T. and D. Machin. On the evaluation of the clinical effects of acupuncture. Pain 16: 111-127, 1983.

[21.] Li, K., J. Zheng and J. Chen. Involvement of spinal protein kinase C in induction and maintenance of both persistent spontaneous flinching reflex and contralateral heat hyperalgesia induced by subcutaneous bee venom in the conscious rat. Neurosci. Lett. 285: 103-106, 2000.

[22.] Luo, C, J. Chen, H.L. Li and J.S. Li. Spatial and temporal expression of c-Fos protein in the spinal cord of anesthetized rat induced by subcutaneous bee venom injection. Brain Res. 806: 175-185, 1998.

[23.] Martin, W. and P. Hartter. Basic peptides in bee venom, VI. Structure-activity studies on the anti-inflammatory effects of derivatives and fragments of the MCD- peptide. Hoppe. Seylers. Z. Physiol. Chem. 361: 525-535, 1980.

[24.] McLellan, A.T., D.S. Grossman, J.D. Blaine and H.W. Haverkos. Acupuncture treatment for drug abuse: a technical review. J. Subst. Abuse Treat. 10: 569-576, 1993.

[25.] Nolano, M., D.A. Simone, G. Wendelschafer-Crabb, T. Johnson, E. Hazen and W.R. Kennedy. Topical capsaicin in humans: parallel loss of epidermal nerve fibers and pain sensation, Pain 81: 135-145, 1999.

[26.] Perrot, S. and C.J. Menkes. Nonpharmacological approaches to pain in osteoarthritis. Available options. Drugs 52 Suppl 3: 21-26, 1996.

[27.] Rashad, S., P. Revell, A. Hemingway, F. Low, K. Rainsford and F. Walker. Effect of non-steroidal anti-inflammatory drugs on the course of osteoarthritis. Lancet 2: 519-522, 1989.

[28.] Robin, L. and E.B. Joan. Treatment efficacy of acupuncture: review of the research literature. Intergrative. Med. 1:107-115, 1998.

[29.] Roos, E.M., M Klassbo and L.S. Lohmander. WOMAC osteoarthritis index. Reliability, validity, and responsiveness in patients with arthroscopically assessed osteoarthritis. Western Ontario and MacMaster Universities. Scand. J. Rheumatol. 28: 210-215, 1999.

[30.] Shkenderov, S. and K. Koburova. Adolapin–a newly isolated analgetic and anti-inflammatory polypeptide from bee venom. Toxicon. 20: 317-321, 1982.

[31.] Somerfield, S.D. and S. Brandwein. Bee venom and adjuvant arthritis. J. Rheumatol. 15: 1878, 1988.

[32.] Thomas, D., D. Cullum, G. Siahamis and S. Langlois. Infrared thermographic imaging, magnetic resonance imaging, CT scan and myelography in low back pain. Br. J. Rheumatol. 29: 268-273, 1990.

[33.] Thomas, M., S.V. Eriksson and T. Lundeberg. A comparative study of diazepam and acupuncture in patients with osteoarthritis pain: a placebo controlled study. Am. J. Chin. Med. 19: 95-100, 1991.

[34.] Ulett, G.A., S. Han and J.S. Han. Electroacupuncture: mechanisms and clinical application. Biol. Psychiatry 44: 129-138, 1998.

[35.] Wand-Tetley, J.I. Historical methods of counter-irritation, Ann. Phys. Med. 3: 90-98, 1956.

Young-Bae Kwon(1), Ji-Hoon Kim(2), Jung-Hee Yoon(3), Jae-Dong Lee(4), Ho-Jae Han(5), Woung-Chon Mar(6), Alvin J. Beitz(7) and Jang-Hern Lee(1)

(1) Department of Veterinary Physiology, College of Veterinary Medicine and School of Agricultural Biotechnology, Seoul National University, Suwon, Korea

(2) Department of East-West Medicine, Graduate School, Kyung Hee University, Seoul, South Korea

(3) Department of Veterinary Radiology, College of Veterinary Medicine, Seoul National University, Suwon, Korea

(4) Department of Acupuncture & Moxibustion, College of Oriental Medicine, Kyung-Hee University, Seoul, Korea

(5) Hormone Research Center, Chonnam National University, Kwang-ju, Korea

(6) Natural Products Research Institute, Seoul National University, Seoul, Korea

(7) Department of Veterinary Pathobiology, College of Veterinary Medicine, University of Minnesota, St Paul, MN, USA

(*) Corresponding author

(Accepted for publication February 1, 2001)

COPYRIGHT 2001 Institute for Advanced Research in Asian Science and Medicine

COPYRIGHT 2001 Gale Group