Hyejung Lee

Bee venom injection into an acupuncture point reduces arthritis associated edema and nociceptive responses

&NA; 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 Freunds 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 Freunds 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.

Tumoral acidic pH-responsive MPEG-poly(β-amino ester) polymeric micelles for cancer targeting therapy

Herein, we evaluated the tumoral low pH targeting characteristics of pH-responsive polymer micelles in cancer targeting therapy. To design the pH-responsive polymeric micelles, hydrophilic methyl ether poly(ethylene glycol) (MPEG) and pH-responsive/biodegradable poly(beta-amino ester) (PAE) were copolymerized using a Michael-type step polymerization, resulting in an MEPG-PAE block copolymer. The amphiphilic MPEG-PAE block copolymer formed polymeric micelles with nano-sized diameter by self-assembly, which showed a sharp pH-dependant micellization/demicellization transition at the tumoral acidic pH value (pH 6.4). For the cancer image and therapy, fluorescence dye, tetramethylrhodamine isothiocyanate (TRITC), or anticancer drug, camptothecin (CPT), was efficiently encapsulated into the pH-responsive polymeric micelles (pH-PMs) by a simple solvent casting method. The TRITC or CPT encapsulated pH-PMs (TRITC-pH-PMs or CPT-pH-PMs) showed rapid release of TRITC or CPT in weakly acidic aqueous (pH 6.4) because they still presented a sharp tumoral acid pH-responsive micellization/demicellization transition. The pH-PMs with 10wt.% of TRITC could deliver substantially more fluorescence dyes to the target tumor tissue in MDA-MB231 human breast tumor-bearing mice, compared to the control polymeric micelles of PEG-poly(l-lactic acid) (PEG-PLLA). Importantly, CPT-pH-PMs exhibited significantly increased therapeutic efficacy with minimum side effects by other tissues in breast tumor-bearing mice, compared to free CPT and CPT encapsulated PEG-PLLA micelles. The tumoral acidic pH-responsive polymeric micelles are highly useful for cancer targeting therapy.

The water-soluble fraction of bee venom produces antinociceptive and anti-inflammatory effects on rheumatoid arthritis in rats.

We recently demonstrated that bee venom (BV) injection into the Zusanli acupoint produced a significantly more potent anti-inflammatory and antinociceptive effect than injection into a non-acupoint in a Freunds adjuvant induced rheumatoid arthritis (RA) model. However, the precise BV constituents responsible for these antinociceptive and/or anti-inflammatory effects are not fully understood. In order to investigate the possible role of the soluble fraction of BV in producing the anti-arthritic actions of BV acupuncture, whole BV was extracted into two fractions according to solubility (a water soluble fraction, BVA and an ethylacetate soluble fraction, BVE) and the BVA fraction was further tested. Subcutaneous BVA injection (0.9 mg/kg/day) into the 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. BVA treatment also reduced the increase in serum interleukin-6 caused by RA induction to levels observed in non-arthritic animals. In addition, BVA therapy significantly reduced arthritis-induced nociceptive behaviors (i.e. nociceptive scores for mechanical hyperalgesia and thermal hyperalgesia). Finally, BVA treatment significantly suppressed adjuvant-induced Fos expression in the lumbar spinal cord at 3 weeks post-adjuvant injection. In contrast, BVE treatment (0.05 mg/kg/day) failed to show any anti-inflammatory or antinociceptive effects on RA. The results of the present study demonstrate that BVA is the effective fraction of whole BV responsible for the antinociception and anti-inflammatory effects of BV acupuncture treatment. Thus it is recommended that this fraction of BV be used for long-term treatment of RA-induced pain and inflammation. However, further study is necessary to clarify which constituents of the BVA fraction are directly responsible for these anti-arthritis effects.

In vivo tumor diagnosis and photodynamic therapy via tumoral pH-responsive polymeric micelles

We report protoporphyrin IX (PpIX) encapsulated pH-responsive micelles for cancer treatment. This system showed pH-responsive micellization/demicellization transition at tumoral acidic pH and enabled in vivo tumor diagnosis and therapy simultaneously.

Does Deqi (needle sensation) exist

The mechanism, by which acupuncture works is not yet clear, therefore there is no unequivocal consensus about styles and sensations of needling. To enhance the scientific base of acupuncture, needling somehow should be objectified. The term Deqi is understood to represent all or at least the main form of phenomena to acupuncture stimulation. The characteristics of Deqi, however, have always been based on a translation of original Chinese description. Hoping to find a clue to develop sham (placebo) method for subject blinding, we investigated which sensations are frequently expected and experienced, and whether or not these expectations and experiences of sensations are similar in naive subjects. The acupuncture sensation scale developed by Vincent et al. (1989) was translated into Korean. Thirty-eight healthy acupuncture naïve female volunteers (mean age 29.1, range 25-39) were asked to complete the sensation scale of acupuncture according to what they expected needling to feel like before needling. Needling was done on left Hegu (LI4) point in the hand and consisted of insertion, stimulation for 30 seconds, and removal. Directly after needling, the subjects were asked to complete the same sensation scale according to what they experienced. The subjects expected to feel hurting, penetrating, sharp, tingling, pricking and stinging, and actually experienced aching, spreading, radiating, pricking and stinging more than 60% of the time. Comparison between expectation and experience, the subjects expected more penetrating, tingling, pricking and burning than they experienced, and on the contrary experienced more aching, pulling, heavy, dull, electric and throbbing than they expected. Traditionally described sensations of Deqi are something beyond just a general pain dimension in the Korean population. Further study involving acupuncture experienced subjects or subjects from other cultures need to confirm this finding. Moreover, sham acupuncture should be studied.

Nicotine-induced behavioral sensitization is associated with extracellular dopamine release and expression of c-Fos in the striatum and nucleus accumbens of the rat

It is well known that repeated injections of nicotine produce progressively larger increases in locomotor activity, an effect referred to as behavioral sensitization. This study was carried out to investigate the neural mechanisms underlying nicotine-induced behavioral sensitization using in vivo microdialysis and Fos-like immunohistochemistry (FLI). Rats were given repeated injections of saline or nicotine (0.4 mg/kg s.c., twice daily for 7 days) followed by one challenge injection on the 4th day after the last daily injection. Systemic challenge with nicotine produced a much larger increase in locomotor activity in nicotine-pretreated rats (659.1+/-94.9 counts/2 h) than in saline-pretreated rats (218.1+/-61 counts/2 h). A direct local challenge of nicotine (1 or 5 mM) via a microdialysis probe in the nucleus accumbens or striatum induced a much greater dose-dependent increase of dopamine (DA) output in nicotine-pretreated rats than in saline-pretreated rats. Furthermore, in parallel with the behavioral and biochemical data, systemic challenge with nicotine produced marked Fos-like immunohistochemistry in the nucleus accumbens and the striatum in the nicotine-pretreated rats. Taken together, this study demonstrates that behavioral sensitization is clearly associated with an increase in DA release and activation of Fos-like immunoreactive cells in the striatum and the nucleus accumbens produced by repeated nicotine treatment. Our results strongly suggest that the striatum and the nucleus accumbens may play a major role in nicotine-induced behavioral sensitization. The present results are discussed in terms of the development and expression of nicotine-induced behavioral sensitization.

Acupuncture prevents 6-hydroxydopamine-induced neuronal death in the nigrostriatal dopaminergic system in the rat parkinson's disease model

Parkinsons disease (PD) is a chronic neurodegenerative disorder, and it has been suggested that treatments promoting survival and functional recovery of affected dopaminergic neurons could have a significant and long-term therapeutic value. In the present study, we investigated the neuroprotective effects of acupuncture on the nigrostriatal system in rat unilaterally lesioned with 6-hydroxydopamine (6-OHDA, 4 microg/microl, intrastriatal injection) using tyrosine hydroxylase (TH) and receptor for brain-derived neurotrophic factor, trkB, immunohistochemistries. Two weeks after the lesions were made, rats presented with asymmetry in rotational behavior (118.3 +/- 17.5 turns/h) following injection with apomorphine, a dopamine receptor agonist (0.5 mg/kg, sc). In contrast, acupunctural treatment at acupoints GB34 and LI3 was shown to significantly reduce this motor deficit (14.6 +/- 13.4 turns/h). Analysis via TH immunohistochemistry revealed a substantial loss of cell bodies in the substantia nigra (SN) (45.7% loss) and their terminals in the dorsolateral striatum ipsilateral to the 6-OHDA-induced lesion. However, acupunctural treatment resulted in the enhanced survival of dopaminergic neurons in the SN (21.4% loss) and their terminals in the dorsolateral striatum. Acupuncture also increased the expression of trkB significantly (35.6% increase) in the ipsilateral SN. In conclusion, we observed that only acupuncturing without the use of any drug has the neuroprotective effects against neuronal death in the rat PD model and these protective properties of acupuncture could be mediated by trkB.

Development and Validation of Acupuncture Fear Scale

Objectives. Strong aversions to acupuncture have been an obstacle to understanding its intrinsic action of acupuncture. Thus, it is necessary to evaluate the nature and extent of fear of acupuncture treatment. Our study aims to develop and validate an instrument that evaluates a patients fear of acupuncture treatment. Methods. We have developed an acupuncture fear scale, a 16-item instrument which assesses the acupuncture fear score and uses it to survey 275 participants in South Korea, thus testing the reliability and validity of the instrument. Results. Internal consistency was high (Cronbachs alpha = 0.935). Test-retest reliability (Spearmans rank correlation coefficient) among 33 participants out of 275 ranged from 0.565 to 0.797 (P < 0.001). Principal component analysis revealed two factors accounting for 68% of the variance, which are painful sensation and possible adverse events, respectively. The acupuncture fear scale was positively correlated with the total of fear of pain questionnaire-III (r = 0.423, P < 0.001). Conclusions. The acupuncture fear scale can be a valid and reliable instrument that can measure fear of acupuncture treatment. These results strongly suggest that it would be a clinically useful tool to assess fear of acupuncture in the acupuncture clinic setting and an important instrument to understand the complex social-behavioral component of acupuncture modality.

Tai Chi Qigong for the quality of life of patients with knee osteoarthritis: a pilot, randomized, waiting list controlled trial

Objective: To evaluate the effects of Tai Chi Qigong training on the quality of life and physical function of patients with osteoarthritis of the knee. Design: A preliminary, single-blind, randomized controlled trial. Setting: General community, performed at Hwaseong City Health Center. Participants: Forty-four elderly subjects (mean age, 69.1 ± 5.4 years) with knee osteoarthritis. Intervention: The patients were randomized (2:1) to: (1) an eight-week Tai Chi Qigong training programme or (2) a waiting list control group. The programme involved eight weeks of group Tai Chi Qigong sessions, with 60 minutes per session twice a week. Main outcome measures: The primary outcome was quality of life measured with the Short Form 36 (SF-36) at baseline and week 8. Secondary outcomes included the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and 6-m walking time. Results: The training group had statistically significant improvements in the quality of life (changes of SF-36, Qigong versus control: 21.6 ± 16.8 versus 9.8 ± 13.6, P<0.05) and 6-m walking test (change in walking time, Qigong versus control: —1.6 ± 1.7 versus —0.2 ± 0.8 s, P<0.01). The WOMAC scores in the training group were markedly improved, although the differences were not statistically significant. Conclusions: Tai Chi Qigong training appears to have beneficial effects in terms of the quality of life and physical functioning of elderly subjects with knee osteoarthritis. However, more rigorous trials are needed to confirm the efficacy of this training for patients with osteoarthritis of the knee.

Effects of acupuncture on chronic corticosterone-induced depression-like behavior and expression of neuropeptide Y in the rats

Repeated injection of corticosterone (CORT) induces dysregulation in the HPA axis, resulting in depression and anxiety. Many studies have shown that acupuncture, which is widely used for the treatment of stress and mental illness, in East Asian countries, is an effective therapeutic intervention for psychosomatic disorders. We investigated the influence of acupuncture therapy on chronic CORT-induced behavioral responses to the forced swimming test (FST) and elevated plus maze (EPM) and expression of neuropeptide Y (NPY) in the rat brain using immunohistochemistry. Male Sprague-Dawley rats were injected with CORT (40 mg/kg, i.p.) once daily for 19 consecutive days. The dysregulation of HPA axis by external injection of CORT was confirmed by measuring the CORT concentration in plasma and the expression level of CRF in hypothalamus. Acupuncture was performed at the PC6 acupoint for 5 min before CORT injection. Acupuncture significantly reduced depression- and anxiety-like behavior and increased NPY expression in the hypothalamus. These results demonstrated that stimulation of the PC6 acupoint suppresses the symptopathology of the hypoactivated HPA axis in chronic CORT-induced rat model of depression.