• Journal of Acupuncture Research
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• v.21 no.6
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• pp.51-62
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• 2004

Objective: To investigate the analgesic effect and its serotonergic mechanism, especially related with 5-HTI and 5-HT2 receptor, of electroacupuncture(EA) in the rat model of collagen-induced arthritis(CIA). Methods : Immunization of male Sprague-Dawley rats with bovine type II (C II) collagen emulsified in Freund's incomplete adjuvant, followed by a booster injection 14 days later, leads to development of arthritis in more than 70% of rats by 21 days postinjection. After three weeks of first immunization, EA stimulation(2 Hz, 0.07 mA, 0.3 ms) was delivered into Jogsamni($ST_{36}$) for 30 minutes. Analgesic effect was evaluated by tail flick latency(TFL). We compared the analgesic effect of EA with TFLs between pretreatment of normal saline and pretreatment of spiroxatrine (5-HT1 receptor antagonist, 1mg/kg, intraperitoneal) and spiperone (5-HT2 receptor antagonist, 1 mg/kg, intraperitoneal) in CIA. Results : 1. TFLs were gradually decreased in CIA as increasing severity of arthritis. 2. Jogsamni($ST_{36}$) EA stimulation in CIA increased TFLs and the effect lasted for 60 minutes. 3. Increased TFLs with Jogsamni($ST_{36}$) EA stimulation were inhibited by pretreatment of spiroxatrine and spiperone in CIA. Conclusions : Jogsamni($ST_{36}$) EA showed analgesic effects in CIA The analgesic effects of Jogsamni($ST_{36}$) EA were inhibited by spiroxatrine and spiperone pretreatment. These observations suggest that 5-HT1 and 5-HT2 serotonergic receptor, which involve the release of serotonin neurotransmitter, play an important roles in analgesic mechanism of EA stimulation.

• Journal of Acupuncture Research
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• v.29 no.3
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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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• v.36 no.3
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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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• v.22 no.2
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• pp.19-32
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• 2005

Objectives : to evaluate the analgesic effect of bee venom acupuncture on Choksamni (ST36) in the collagen-induced arthritis rats and investigate the role played by serotonergic receptor subtypes (5-HT1a, 5-HT2a) in the antinociceptive effect of bee venom acupuncture in a thermal hyperalgesia test Methods : Experiments were performed on 5 week-aged 60 male Sprague-Dawley rats according to National Institute of Health guidelines and the ethical guidelines of the International Association for the Study of Pain (IASP). Arthritis was induced with arthrogenic collagen emulsion (Bovine type II collagen ${\mu}g$ with incomplete Freund's adjuvant $100\;{\mu}g$). The onset of arthritis was considered to be present when erythema and swelling were detected in at least one joint. The thermal hyperalgesia was evaluated weekly with tail flick test in the rats of severity grade 3 without any injury at tail and foot (including inflammation, ulceration, snap). In the fourth week after first immunization, the analgesic effect of bee venom acupuncture (Choksamni, ST36) was measured with consecutive tail flick latency after intraperitoneal injection of spiroxatrine (1mg/kg) and spiperone (1mg/kg). Results : Chronic inflammatory pain was induced as time elapsed after the immunization of arthrogenic collagen and the maximum value was reached from third to fifth week. Chronic inflammatory pain induced by CIA was inhibited by bee venom acupuncture on the left ST36. The analgesic effect of bee venom acupuncture was inhibited by intraperitoneal injection of 5-HT1a antagonist spiroxatrine and 5-HT2a antagonist spiperone. Conclusions : Therefore, a conclusion. that the analgesic effect of bee venom acupuncture in the chronic inflammatory pain is partially mediated by 5-HT1a and 5-HT2a receptors can be made.

• Journal of Acupuncture Research
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• v.22 no.2
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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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• v.40 no.2
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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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• v.19 no.4
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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.

• Korean Journal of Pharmacognosy
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• v.42 no.3
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• pp.246-252
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• 2011

Korean mistletoe Lectin (KML-C) is composed of A and B sub-chain. B chain binds to carbohydrates on cell surface and A chain hinders translation and induces an apoptosis as a RIP (ribosome inactivating protein). KML-C has very strong biological activities, it has seriously limits to use as a cancer therapy or adjuvant because of its toxicity to normal cells. This study is therefore conducted to see if B chain of KML-C might have immunological activity, especially adjuvant activities with less toxicity. We isolated B chain from KML-C using the lactose affinity chromatography, and examined their immunoadjuvant activity. The isolated B-chain did not show any cytotoxicity against tumor cell, RAW264.7, and P388D1 while KML-C had a very strong toxicity. This non-toxic effect was observed also by in-vivo study. Both humoral and cellular immunities were observed ; the antibody titer was increased when the mice were immunized with B-chain used as adjuvant like Freund's adjuvant, indicating that B chain of mistletoe lectin alone might be used for adjuvant; it also increased DTH in cellular immunity. These results suggest that B-chain of KML-C might be used for adjuvant used for the production of antibody or vaccine with less toxicity.

• International Journal of Oral Biology
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• v.46 no.3
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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.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2001.11a
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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.