• Journal of Acupuncture Research
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• 제29권3호
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• pp.55-65
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• 2012

Objectives : The purpose of this study was find out the therapeutic effects of Ulmus davidiana Planch pharmacopuncture(UPP) on the mice with collagen-induced rheumatoid arthritis. Methods : UPP was prepared and tested for therapeutic potential of rhematoid arthritis by measuring the inhibition of cyc1ooxgenase-2(COX-2) and phospholipase A2(PLA2) activities in mice. Results : UPP showed therapeutic effects on collagen-induced rheumatoid arthritis on week 8 and week 9. UPP also inhibited Freund's complete adjuvant induced chronic rheumatoid arthritis in mice. UPP showed significant inhibition of type I and type II PLA2 activities in a dose dependent manner. However, PGE2 Production was not decreased with UPP and lipopolysaccharide-induced COX-2 protein expression was not inhibited by UPP. Conclusions : These results suggest that UPP has an therapeutic effects on drug induced-rheumatoic arthritis by inhibiting PLA2 activity.

• International Journal of Oral Biology
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• 제36권3호
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• pp.143-148
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• 2011

The present study investigated the role of peripheral P2X receptors in inflammatory pain transmission in the orofacial area in rats. Experiments were carried out on male Sprague-Dawley rats weighing 220 to 280 g. Formalin (5%, 50 ${\mu}L$) and complete Freund's adjuvant (CFA, 25 ${\mu}L$) was applied subcutaneously to the vibrissa pad to produce inflammatory pain. TNP-ATP, a $P2X_{2,2/3,4}$ receptor antagonist, or OX-ATP, a $P2X_7$ receptor antagonist, was then injected subcutaneously at 20 minutes prior to formalin injection. One of the antagonists was administered subcutaneously at three days after CFA injection. The subcutaneous injection of formalin produced a biphasic nociceptive behavioral response. Subcutaneous pretreatment with TNP-ATP (80, 160 or 240 ${\mu}g$) significantly suppressed the number of scratches in the second phase produced by formalin injection. The subcutaneous injection of 50 ${\mu}g$ of OX-ATP also produced significant antinociceptive effects in the second phase. Subcutaneous injections of CFA produced increases in mechanical and thermal hypersensitivity. Both TNP-ATP (480 ${\mu}g$) and OX-ATP (100 ${\mu}g$) produced an attenuation of mechanical hypersensitivity. However, no change was observed in thermal hypersensitivity after the injection of either chemical. These results suggest that the blockade of peripheral P2X receptors is a potential therapeutic approach to the onset of inflammatory pain in the orofacial area.

• Journal of Acupuncture Research
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• 제22권2호
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• pp.33-41
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• 2005

Objective : The effect of Ulmus davidiana Planch(UD), which has long been known to have anti-inflammation and protective effects on damaged tissue, inflammation and bone among other functions, on the development of type II collagen (CII)-induced arthritis (CIA) in rats was studied. Methods : Male rats were immunized with an emulsion of $200\;{\mu}g$ of CII and complete Freund's adjuvant (CFA). The rats were then given intraperitoneal stimulation of Ulmus davidiana Planch herbal acupuncture(UDHA)or saline during the experiment. When compared with rats treated with saline as control, UDHA at doses of more than $20{\mu}g/100\;g$ rat once a day for 7 days inhibited the ability of inguinal lymph node cells to produce T cell cytokines interleukin-2, interleukin-6, $IFN-{\gamma}$ when the cells were obtained from rats 14 days after immunization and cultured in vitro with CII. Results : When rats were injected intraperitoneally, UD -treated group and control group rats did not differ significantly when low doses of UD was given to rats. Conclusion : The recommended dose of UD in the management and treatment of rat CIA will be more than $20{\mu}g/100\;g$, which is two-firth of human therapeutic dose. From the results, it was concluded that the effect of UDHA is dependent of dosage.

• International Journal of Oral Biology
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• 제40권2호
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• pp.71-77
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• 2015

The activation of glial cells in the spinal cord has been contribute to the initiation and maintenance of pain facilitation induced by peripheral inflammation and nerve injury. The present study investigated effects of botulinum toxin type A (BoNT-A), injected subcutaneously or intracisternally, on the expression of microglia and astrocytes in rats. Complete Freund's Adjuvant (CFA)-induced inflammation was employed as an orofacial chronic inflammatory pain model. A subcutaneous injection of $40{\mu}L$ CFA into the vibrissa pad was performed under 3% isoflurane anesthesia in SD rats. Immunohistochemical analysis for changes in Iba1 (a microglia marker) and GFAP (an astrocyte marker), were performed 5 days after CFA injection. Subcutaneous injection of CFA produced increases in Iba1 and GFAP expression, in the ipsilateral superficial lamia I and II in the medullary dorsal horn of rats. Subcutaneous treatment with BoNT-A attenuated the up-regulation of Iba1 and GFAP expressions induced by CFA injection. Moreover, intracisternal injection of BoNT-A also attenuated the up-regulated Iba1 and GFAP expressions. These results suggest that the anti-nociceptive action of BoNT-A is mediated by modulation activation of glial cells, including microglia and astrocyte.

• The Korean Journal of Physiology and Pharmacology
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• 제19권4호
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• pp.349-355
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• 2015

We examined the effects of peripherally or centrally administered botulinum neurotoxin type A (BoNT-A) on orofacial inflammatory pain to evaluate the antinociceptive effect of BoNT-A and its underlying mechanisms. The experiments were carried out on male Sprague-Dawley rats. Subcutaneous (3 U/kg) or intracisternal (0.3 or 1 U/kg) administration of BoNT-A significantly inhibited the formalin-induced nociceptive response in the second phase. Both subcutaneous (1 or 3 U/kg) and intracisternal (0.3 or 1 U/kg) injection of BoNT-A increased the latency of head withdrawal response in the complete Freund's adjuvant (CFA)-treated rats. Intracisternal administration of N-methyl-D-aspartate (NMDA) evoked nociceptive behavior via the activation of trigeminal neurons, which was attenuated by the subcutaneous or intracisternal injection of BoNT-A. Intracisternal injection of NMDA up-regulated c-Fos expression in the trigeminal neurons of the medullary dorsal horn. Subcutaneous (3 U/kg) or intracisternal (1 U/kg) administration of BoNT-A significantly reduced the number of c-Fos immunoreactive neurons in the NMDA-treated rats. These results suggest that the central antinociceptive effects the peripherally or centrally administered BoNT-A are mediated by transcytosed BoNT-A or direct inhibition of trigeminal neurons. Our data suggest that central targets of BoNT-A might provide a new therapeutic tool for the treatment of orofacial chronic pain conditions.

• International Journal of Oral Biology
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• 제46권3호
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• pp.119-126
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• 2021

Activation of transient receptor potential vanilloid 1 (TRPV1), a calcium permeable channel expressed in primary sensory neurons, induces the release of glutamate from their central and peripheral afferents during normal acute and pathological pain. However, little information is available regarding the glutamate release mechanism associated with TRPV1 activation in primary sensory neurons. To address this issue, we investigated the expression of vesicular glutamate transporter (VGLUT) in TRPV1-immunopositive (+) neurons in the rat trigeminal ganglion (TG) under normal and complete Freund's adjuvant (CFA)-induced inflammatory pain conditions using behavioral testing as well as double immunofluorescence staining with antisera against TRPV1 and VGLUT1 or VGLUT2. TRPV1 was primarily expressed in small and medium-sized TG neurons. TRPV1+ neurons constituted approximately 27% of all TG neurons. Among all TRPV1+ neurons, the proportion of TRPV1+ neurons coexpressing VGLUT1 (VGLUT1+/TRPV1+ neurons) and VGLUT2 (VGLUT2+/TRPV1+ neurons) was 0.4% ± 0.2% and 22.4% ± 2.8%, respectively. The proportion of TRPV1+ and VGLUT2+ neurons was higher in the CFA group than in the control group (TRPV1+ neurons: 31.5% ± 2.5% vs. 26.5% ± 1.2%, VGLUT2+ neurons: 31.8% ± 1.1% vs. 24.6% ± 1.5%, p < 0.05), whereas the proportion of VGLUT1+, VGLUT1+/TRPV1+, and VGLUT2+/TRPV1+ neurons did not differ significantly between the CFA and control groups. These findings together suggest that VGLUT2, a major isoform of VGLUTs, is involved in TRPV1 activation-associated glutamate release during normal acute and inflammatory pain.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2001년도 추계학술대회 및 정기총회
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• pp.84-84
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• 2001

The heartwood of Rhus verniciflua has been known to be effective for lingering intoxication and diabetes mellitus and rheumatoidal arthritis in traditional folk medicine in Korea. We have previously reported that antimutagenic effect of flavonoids derived from the heartwood extract of R. verniciflua, and sulfuretin was the active component. Recently, we have demonstrated that sulfuretin could be an anti-inflammatory principle of the R. verniciflua heartwood partially dependent on cyclooxigenase-inhibitory activity. The present study was undertaken to demonstrate the anti-rheumatoidal arthritis effect of the R. verniciflua heartwood extract, its EtOAc fraction and the main flavonoids, sulfuretin and fustin. All the test samples showed variably significant inhibitory effects on hind paw edema induced by Freund's complete adjuvant reagent (FCA reagent). Sulfuretin treatment with 10 mg/kg (i.p.) for seven days showed the inhibitory effect of 54.2${\pm}$3.0%, Similar trends in RA- and CRP tests, vascular permeability test and trypsin inhibitor test were also found. In addition, no dead mouse was found even when the dose was increased up to 5,000 mg/kg (i.p.). Treatment with 250-1,500 mg/kg on normal rats did not show any marked toxicological significances in the tests of body weight gain, wet weight of organs and hepatic functions. These results suggested that the heartwood of R. verniciflua could be an adequate crude drug for rheumatoidal arthritis with an active component of sulfuretin. The toxicological safety of the heartwood of R, verniciflua is contrasted to known severe allergenic action of the stem bark or its exudate.

• Korean Journal of Acupuncture
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• 제39권4호
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• pp.132-141
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• 2022

Objectives : Some acupoints are commonly utilized to treat a variety of diseases. The acupoints appear to have a wide range of effects caused by several mechanisms. The purpose of this study is to investigate into the potential role of microRNAs (miRNAs) in the multipotent effects of individual acupoint stimulation. Methods : We examined the miRNA expressions in the dorsal root ganglia (DRG) of neuropathic or inflammatory pain rats following ST36 and GB34 electroacupuncture (EA) stimulation. Neuropathic pain was induced by L5 spinal nerve ligation. Inflammatory pain was induced by knee joint injection of Complete Freund's adjuvant (CFA). EA was given under gaseous anesthesia with the same parameters (1mA, 2Hz, 30 min) in 5 consecutive days. Pain behaviors and miRNA expressions were analyzed. Results : In rats with neuropathic and inflammatory pain, EA treatments significantly enhanced the paw withdrawal threshold and weight-bearing force. After nerve injury, 36 miRNAs were upregulated in the DRG of neuropathic rats, while EA downregulated 10 of them. Furthermore, 14 miRNAs were downregulated following nerve damage, while one was increased by EA. 15 miRNAs were increased in the DRG of inflammatory rats following CFA injection, while 5 were downregulated by EA. Furthermore, 17 miRNAs were downregulated following CFA injection, while 7 were increased by EA. The miRNAs rno-miR-335, rno-miR-381-5p, rno-miR-1306-3p, and rno-miR-1839-3p were regulated by EA in both models. Conclusions : In two pain models, EA applied to ST36 and GB34 regulated miRNA expression differently. There appeared to be both acupoint-specific and non-specific miRNAs, and miRNA regulation of differential protein expression may modulate a variety of EA mechanisms.

• 대한약침학회지
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• 제26권3호
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• pp.257-264
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• 2023

Objectives: The study was designed to evaluate anti-arthritic activity of Ajmodadi Churna (AC) and its effect on Complete freund's adjuvant (CFA)-induced arthritis in Wistar rats. Methods: Arthritis was induced by injecting 0.2 mL CFA into sub plantar surface of left hind paw. Test sample AC-1 and AC-2, 200 and 400 mg/kg, respectively was given to the animals for 21 consecutive days. The increase in swelling was observed after induction of arthritis. The paw edema was measured on 0, 3, 7, 14 and 21 day using Vernier caliper after the induction of arthritis. The collected blood samples further used for the estimation of red blood cells (RBC), white blood cells (WBC), erythrocytes sedimentation rate (ESR), and hemoglobin (Hb), using hematology analyzer. Serum concentration of IL-6 and TNF-α were also measured using rat ELISA kits. Results: Results showed that a significant reduction in paw edema was observed in AC-2 treated rats. The paw edema was restored on day 21 was 4.48 mm for AC-2, which is near to the control group. The arthritis score in treated rats was found to be considerably lower than in the control group i.e. 0.83 for AC-2 and 1.50 for AC-1. A decrease in levels of RBC and hemoglobin were observed in arthritic rats. Inflammation was significantly reduced and serum levels of IL-6 and TNF-α were lowered after treatment with the test drug. Conclusion: It can be concluded from the study that AC possess significant anti-arthritic activity. Furthermore, this condition was linked to a reduction in abnormal humoral immune responses.

• 대한약침학회지
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• 제5권1호
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• pp.113-133
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• 2002

Objective: To investigate effects of Cervi Cornu on Adjuvant Athritis in rats, the edema inhibit rate, the anaJgesic effects, the number of WBC, RA facter, Platelet, the quantity of CRP, total protein, albumin and globuline in the blood serum were measured in the arthritis part. Results: The results obtained as fonows ; 1. After arthritis of Sprague dawley(SD) rats was induced by injecting Freund's complete adjuvant for 2 weeks, any treatment was not for Control group, acupunctured for Treat Ⅰ group. normal saJine was ora] administrated for the Treat Ⅱ group, Cervi Cornu Ex. was oral administrated for Treat Ⅲ, and Cervi Cornu Herbal-acupullcture was injected for Trea Ⅳ group during 2 weeks every other day. Selected point was on pressure pain point in both groups. And then the edema inhibit rate were checked. The edema inhibit rate was $46.03\%$ in Treat I group, $43.24\%$ Treat IV group, $37.44\%$ in Treat III. there was significance in the edema inhibit rate between Control group and Treat group, in order of Treat Ⅰ, Ⅳ, Ⅲ.(p<0.05) 2. The analgesic effects was $7.58{\pm}1.80$(${\times}10$gm) in Control group. $11.00{\pm}1.10$(${\times}10$gm) in Treat Ⅰ group. $99.92{\pm}1.28$(${\times}10$gm) in Treat Ⅲ group and $14.67{\pm}1.03$(${\times}10$gm) in Treat Ⅳ group. There was significance in the analgesic effects between Control group and Treat group(p<0.05) 3. The number of WBC was $14.72{\pm}1.48$(${\times}10^3$㎕) in control Group, $10.26{\pm}1.13$(${\times}10^3$㎕) in Treat Ⅰ group, $11.00{\pm}1.13$(${\times}103$㎕) in Treat Ⅱ Group and $9.63{\pm}1.75$(${\times}10^3$㎕) in Treat Ⅳ group. There was significance in the number of WBC between Control group and Treat group(p<0.05) 4. The content of total protein in the blood serum were $6.13{\pm}0.05$g/dl in control group, $5.73{\pm}0.14$g/dl in Treat I group, $5.88{\pm}0.13$g/dl in Treat Ⅲ group and $5.90{\pm}0.13$g/dl in Treat IV group. There was significance in The content of total protein in the blood serum between Control group and Treat group(p<0.05) 5. The contests of albumin in the blood serum were $2.32{\pm}0.12$g/dl in the Control group, $2.35{\pm}0.05$g/dl in Treat Ⅰ group, $2.35{\pm}0.05$g/dl in Treat Ⅱ group, $2.30{\pm}0.06$g/dl in Treat Ⅲ group, $2.42{\pm}0.08$g/dl in Treat IV group. There was no significance in The content of albumin in the blood serum between Control group and Treat group(p<0.05) 6. The contests of globulin in the blood semm were $3.68{\pm}0.08$g/dl in the Control group, $3.43{\pm}0.12$g/dl in Treat Ⅰ group, $3.55{\pm}0.10$g/dl in Treat IV group. There was significance in The content of globulin in the blood serum between Control group and Treat group(p<0.05) 7. The numbers of RA factor were $3.47{\pm}0.54$IU/ml in Control group and $2.38{\pm}0.50$IU/ml in Treat Ⅱ group. There was significance inThe numbers of RA factor between Control group and Treat group(p<0.05) 8. The numbers of platelet were $1126.33{\pm}1126.33{\pm}85.93{times}10^3$/㎕ in Control group, $1043.33{\pm}80.80{times}10^3$/㎕ in Treat Ⅰ group, $1116.82{\pm}77.93{times}10^3$/㎕ in Treat Ⅱ group, $1164.17{\pm}94.02{times}10^3$/㎕l in Treat Ⅲ group, $1076.67{\pm}54.84{times}10^3$/㎕ in Treat Ⅳ group. There was no significance in The numbers of platelet between Control group and Treat group(p<0.05) 9. The quantity of CRP were $0.05{\pm}0.01$mg/ml in Control group, $0.05{\pm}0.01$mg/ml in Treat Ⅰ group, $0.06{\pm}0.01$mg/ml in Treat Ⅱ group, $0.05{\pm}0.00$mg/ml in Treat Ⅲ group, $0.05{\pm}0.00$mg/ml in Treat Ⅳ group. There was no significance in The quantity of CRP between Control group and Treat group(p<0.05) Concluslon : From these results, it is shown Cervi Comu Herbal-acupuncture more efffective thaJJ Cervi Cornu Ex. on Adjuvant Arthritis in rats.