• The Korean Journal of Pain
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• v.11 no.2
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• pp.194-200
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• 1998

Background: Effect of nitric oxide on the hyperalgesia induced by inflammation is controversial. We attempted to find out the peripheral effects of nitric oxide (NO) on hyperalgesia induced by Freund's complete adjuvant (FCA) induced inflammation. Methods: Male Sprague Dawley rats were divided into three groups; control, low dose NG-nitro-L-arginine methyl ester (L-NAME, 500 ug), high dose L-NAME (5 mg). Inflammation was induced by injecting 0.1 ml of FCA intraplantarly, which shows typical hyperalgesia within twelve hours after injection and maintained for about one week. Drugs were injected 2 hours before, just before, and 3, 6, 9, 12 hours after the injection of FCA. Effect of L-NAME on hyperalgesia was assessed by measuring mechanical hyperalgesia and spontaneous pain for 3 days. Results: When injected at the site of inflammation, L-NAME caused dose dependent reduction of spontaneous hyperalgesia. Mechanical hyperalgesia was also reduced by high dose L-NAME (p<0.05). After systemic injection of high dose L-NAME in the back, no significant difference was noticed. Conclusions: This suggest that L-NAME reduces FCA induced hyperalgesia via peripheral action.

• Physical Therapy Korea
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• v.15 no.1
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• pp.69-76
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• 2008

This study was designed to determine the effects of swimming and low power laser on rheumatoid arthritis in Sprague-Dawley rats. Rheumatoid arthritis was induced in 36 rats among 48 Sprague-Dawley rats by the subcutaneous injection of .05 $m{\ell}$ Freund's Complete Adjuvant into the right hind paw and .05 $m{\ell}$ Freund's Complete Adjuvant into the right hind knee joint capsule. A second injection was performed by the same method using .1 $m{\ell}$ Freund's Complete Adjuvant per a rat. Arthritic rats were divided into 8 groups: each 1 week and 2 weeks of arthritic swimming, arthritic laser, arthritic case control and normal group. In this study, several experimental tests were performed to determine the concentration of Interleukin-6, the space of the knee joint and the thickness of the hind paw. The concentration of Interleukin-6 and hind paw thickness decreased in the swimming group and laser group as compared to the control group. The space of the knee joint increased significantly after the swimming exercise. Swimming and low power laser therapy positively affect rheumatoid arthritis in rats affect by decreasing the concentration of Interleukin-6 and hind paw thickness, and increasing the space of the knee joint.

• Journal of Acupuncture Research
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• v.22 no.4
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• pp.55-63
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• 2005

목적 : 만성 염증성 질환에 대한 전침효과를 알아보기 위해 complete Freund's adjuvant (CA) 유발 관절염 모델에서 염증관련 단백질의 변화를 살펴보았다. 방법 : Sprague-Dawley계 흰쥐의 족부에 CFA를 주사한 다음 3일 간격으로 2 Hz, 15 Hz 및 120 Hz 전침 자극을 주며 부종 형성여부를 plethysmometer로 측정하여 판정하였으며 30일 째 거퇴관절을 취하여 4% paraformaldehyde에 고정하고 EDTA용액에서 탈회시켜 파라핀연속 절편을 얻어 $NF-{\kappa}B$를 비롯한 5종의 염증관련 단백질의 발현을 면역조직화학적으로 살펴보았다. 결과 : 관절연골내 면역반응 중 연골기질은 반응이 없거나 약하고 연골세포는 $NF-{\kappa}Bp65,\;I-{\kappa}B{\alpha},\;iNOS$반응이 강하며 특히 유리연골층에서 더 현저하였으나 염증 및 전침자극에 따른 변화는 없었다. 관절낭에서 면역반응을 살펴보면 염증유발시 활액세포의 면역반응세포는 $I-{\kappa}B{\alpha}$가 감소한 반면 iNOS, $IL-1{\beta}$는 증가하며 특히 iNOS 증가가 현저하였으며 전침자극에 의해 iNOS가 감소하였다. 활액막조직에서 모든 면역반응이 증가하며 특히 $NF-{\kappa}Bp65,\;I-{\kappa}B{\alpha},\;iNOS$ 반응이 현저한데 전침자극에 의해 $IL-1{\beta}$를 제외한 모든 반응이 감소하였다. 결론 : 만성 염증성 동물모델의 거퇴관절 내 염증관련 단백질은 관절연골보다 관절낭에서 큰 변화를 보이며 전침처치에 의해 이들 단백질 발현이 억제되는 것으로 보아 전침이 만성 염증성 질환에 효과적임을 알 수 있다.

• Journal of Acupuncture Research
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• v.32 no.2
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• pp.65-75
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• 2015

Objectives : The purpose of this study was to investigate the effects of warm needling at $GB_{30}{\cdot}GB_{34}$ on Complete Freund's Adjuvant(CFA)-induced rheumatoid arthritis in rats. Methods : Arthritis was induced by injecting CFA subcutaneously into the left knee joint and paw. Acupuncture(AT) and warm needling(W-AT0.5, W-AT1.0) were injected at $GB_{30}{\cdot}GB_{34}$, every other day for a total of 5 times beginning on day 10 after the CFA injection. Thereafter, external shape, paw edema, serum aminotransferase and anti-inflammatory factors were assessed, and hematological and histological observations were made. Results : In paw edema volume all 3 groups(AT, W-AT0.5, W-AT1.0) showed significant decrease compared to the CFA control group. In TNF-${\alpha}$ and IL-6, all 3 groups showed significant decrease compared to CFA control group. In AST and ALT all 3 groups showed no significant change. In IL-$1{\beta}$, W-AT0.5 and W-AT1.0, groups showed significant decrease compared to the CFA control group. Leucocyte, erythrocyte and thrombocyte, all 3 groups showed no significant change. In histological observations, all 3 groups were similar to the intact group in terms of synoviocyte, cartilage lacuna and cartilage cells. Conclusions : The results suggest that warm needling at $GB_{30}{\cdot}GB_{34}$, has the effect of suppressing inflammation of CFA-induced rheumatoid arthritis in rats.

• Journal of Pharmacopuncture
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• v.6 no.2
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• pp.29-43
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• 2003

9Objective : We carried out this experimental study in order to investigate the effect of Chaenomelis Fructus(木瓜) extract and herbal-acupuncture on the arthritis induced by injecting Freund's complete adjuvant Method : 1. We categorized SD-rats into five groups as followings. (1) Control: Without any Treat (2) Treat I: treated by acupuncture (3) Treat II: treated by drinking 5% saline (4) Treat III: treated by drinking Chaenomelis Fructus(木瓜) extract (5) Treat IV: treated by Chaenomelis Fructus(木瓜) herbal-acupuncture 2. We established ten items for decision of experimental results as followings Edema rate, Pain endurance, WBC, Hemoglobin, Platelet, Total protein, Albumin, Globulin, RA factor, CRP Results : The groups that showed significant effects compared with Contol group were explained as followings. 1. Edema rate : Treat I , Treat III 2. Pain endurance : Treat I, Treat IV 3. WBC : Treat IV 4. Hemoglobin : Treat III 5. Plat99elet : Treat IV 6. Total protein : Treat I, Treat IV 7. Albumin : None 8. Globulin : Treat I, Treat IV 9. RA factor : Treat I, Treat IV 10. CRP : Treat IV Conclusion : Observing above experimental results, we can guess that the effects of acupuncture and Chaenomelis Fructus(木瓜) herbal-acupuncture on Freund's adjuvant arthritis are more superior than other ways. In addition, we can find that the latter is more better than the former in effect by two items(platelet, CRP).

• Journal of Acupuncture Research
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• v.20 no.3
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• pp.117-130
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• 2003

To study the analgesic and effect and its mechanism of eletroacupunture(EA) on the chronic inflammatory pain 50 rats were induced with arthralgesia by injecting complete freund's adjuvant(CFA). Two weeks after the injection of CFA, EA stimulation(2Hz, 0.07mA, 0.3ms) was delivered to Jogsamni($ST_{36}$) for 20 minutes. Analgesic effect was evaluated by using the tail flick latency(TFL) and the analgesic mechanism was observed by applying TFL with the pretreatment with naloxone and yohimbine. The results were as follows ; 1. TFL level for the model of adjuvant-induced arthritis decreased as time went by and it induced the hyperalgesia. 2. EA stimulation delivered to Jogsamni($ST_{36}$) for 20 minutes in the rat model of adjuvant-induced arthritis brought analgesic effect and its effect had lasted for 40 minutes after the stimulation. 3. The analgesic effect of Jogsamni($ST_{36}$) EA in the rat model of adjuvant-induced arthritis was blocked by pretreatment with naloxone(2mg/kg,i.p). This result suggests that the EA effect on the chronic inflammatory pain can be related to the endogenous opioid mechanism. 4. The analgesic effect of Jogsamni($ST_{36}$) EA in the rat model of adjuvant-induced arthritis was blocked by pretreatment with naloxone(2mg/kg,i.p). This result suggests that the EA effect on the chronic inflammatory pain can be related to the ${\alpha}_2$-adrenergic mechanism.

• The Korean Journal of Pain
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• v.13 no.2
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• pp.164-174
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• 2000

Background: After an injury to tissue such as the skin, hyperalgesia develops. Hyperalgesia is characterized by an increase in the magnitude of pain evoked by noxious stimuli. It has been postulated that in the mechanism of hyperalgesia (especially secondary hyperalgesia) and allodynia, a sensitization of central nervous system such as spinal dorsal horn may contribute to development of hyperalgesia. However, the precise mechanism is still unclear. In the present study, we investigated the roles of N-methyl-D-aspartate (NMDA) receptor and nitric oxide (NO) system in the mechanism of hyperalgesia, and their relations with c-fos expression Methods: Inflammation was induced by injection of complete Freund adjuvant (CFA) into unilateral hindpaw of Sprague-Dawley rat. Behavioral studies measuring paw withdrawal responses by von Frey filaments and paw withdrawal latencies by radiant heat stimuli and stainings of nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase and c-fos immunoreactivity were performed. The effects of MK-801, an NMDA receptor blocker and $N^\omega$-nitro-L-arginine (L-NNA), a nitric oxide synthase (NOS) inhibitor were evaluated. Results: 1) Injection of CFA induced mechanical allodynia, mechanical hyperalgesia and thermal hyperalgesia. And it increased the number of NADPH-diaphorase positive neurons and c-fos expression neurons. 2) MK-801 inhibited mechanical hyperalgesia and thermal hyperalgesia induced by CFA and reduced the number of NADPH-diaphorase positive neurons and c-fos expression neurons. 3) L-NNA inhibited the thermal hyperalgesia and reduced the number of NADPH-diaphorase positive neurons, but did not affect the number of c-fos expression neurons. Conclusions: These results suggest that in the mechanism of mechanical hyperalgesia, NMDA receptor but not NO-system is involved and in the case of thermal hyperalgesia both NMDA receptor and NO system are involved. NO system did not affect the expression of c-fos, but c-fos expression and NOS activity were dependent on the activity of NMDA receptor.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.2
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• pp.484-489
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• 2004

Objective : In order to study the effects of Herba ChelidoniiㆍClematis Florida ThunbㆍChaenomelis Fructus complex herbal acupuncture on anti-inflammation and liver in rats with arthritis induced Freund's complete adjuvant. Method : We performed several experimental items : that is edema value, numbers of WBC. total protein, total bilirrubin, SGOT, SGPT. Result: The change in the right plantar edema shows that Control group was reduced by 0% but, ST group ,Sample A group and Sample B group were reduced by 287.2%, 343.0%, 272.5% respectively. In the WBC count, ST group, Sample A group, Sample B group showed a decrease with statistical significance as compared with control group. In the total protein, Sample B group showed a decrease with statistical significance as compared with control group. In the total bilirrubin, SGOT, SGPT, None showed noxious variation with statistical significance as compared with control group. Conclusion : As a result of this experiment, it is concluded that Herba ChelidoniiㆍClematis Florida ThunbㆍChaenomelis Fructus complex herbal acupuncture showed that therapeutic effect of anti-inflammation in adjuvant arthritis and non-toxic effect of liver.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.2
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• pp.446-450
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• 2004

Objectives: In order to study the effects of Harpagophyti Radix in rats with arthritis induced by Freund's complete adjuvant. Methods : In this study, rats with arthritis induced by Freund's complete adjuvant were divided into four groups; Normal, Control, Sample A(Harpagophyti Radix 6mg/200g) and Sample B(Harpagophyti Radix 12mg/200g). After 1 week, separated searches were made on the change of edema rate, the count of WBC, the quantity of total protein, total bilirubin, GOT and GPT in the serum. Results: In the right plantar edema, both of Sample groups showed a decrease in comparison with Control group. In the count of WBC, the quantity of serum total protein and SGOT, Sample B showed a decrease with statistical significance in comparison with Control group. In the quantity of serum total bilirubin and SGPT, both of Sample groups did not show any harmful change in in comparison with Control group. Conclusion : Reviewing these experimental results, it appeared that Harpagophyti Radix showed the therapeutic effect of anti-inflammatation on adjuvant arthritis.

• Natural Product Sciences
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• v.16 no.3
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• pp.159-163
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• 2010

A mixture of several detoxified bacterial strains ($Sterodin^{(R)}$) has been studied for anti-inflammatory effect in Wistar rats on carrageenin, dextran and prostaglandin $E_1$ ($PGE_1$) induced edema in acute model and cotton pellet and carrageenin induced sub-acute model, while, Freund's adjuvant induced chronic model. The bacterial strains showed strong inhibitory activity in acute, sub-acute and chronic models of inflammation. Further, it reduced ${\alpha}1$ acid glycoprotein and ${\alpha}2$ macroglobulin levels in serum and prostaglandin $E_2$ in inflamed paw. These results indicated that the bacterial strains probably act through prostaglandin mediatory pathways and may be useful in treatment of inflammation.