• Proceedings of the PSK Conference
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• 2002.10a
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• pp.371.1-371.1
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• 2002

Triterpenoids. Ursolic acid (1). 23-hydroxyursolic acid (2). and tormentic acid (3) were obtained by the hydrolysis of BuOH fraction of Cussonia bancoensis extract and further chromatographic isolation to test antinociceptive and anti-inflammatory effect of C. bancoensis (Aratiaceae). Compound 1 and 2 exhibited anti-nociceptive effects, which were determined by acetic acid-induced writhing test and hot plate test. However. the effect of tormentic acid was not significant (omitted)

• YAKHAK HOEJI
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• v.51 no.6
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• pp.508-516
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• 2007

Thymus magnus is an endemic (Ulleung Island) species in Korea. This plant is used as diaphoretics and carminatives in traditional medicine. In the literature, few scientific assays were realized on this species, such as antibiotic (Streptococcus pneumoniae, Staphylococcus aureus, Salmonella enteritidis, and S. typhimurium) and antifungal activities. In order to clarify whether essential oil of T. magnus have pharmacological effects, anti-inflammatory, sedative, anti-depressant, analgesic, and sleep-prolonged effects were investigated using animal models. From this study, the following conclusions were attained; 1) Essential oil of T. magnus did not show any acute toxicity on mice when orally administered at the dose of 2-3 g/kg body weight. 2) Essential oil of T. magnus possessed strong anti-inflammatory activity, similar to that of a positive control prednisolone. 3) Essential oil of T. magnus had excellent analgesic activity, comparable to that of aspirin. 4) The essential oil of T. magnus possessed strong sleep-prolonged effect on pentobarbital induced-sleep test in mice model. 5) In the hot plate test, the essential oil of T. magnus had moderate effect. 6) And the essential oil of T. magnus had no significant effects in forced-swimming test and open-field test.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.1
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• pp.65-74
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• 2017

Here we investigated the central processing mechanisms of mechanical allodynia and found a direct excitatory link with low-threshold input to nociceptive neurons. Experiments were performed on male Sprague-Dawley rats weighing 230-280 g. Subcutaneous injection of interleukin 1 beta ($IL-1{\beta}$) ($1ng/10{\mu}L$) was used to produce mechanical allodynia and thermal hyperalgesia. Intracisternal administration of bicuculline, a gamma aminobutyric acid A ($GABA_A$) receptor antagonist, produced mechanical allodynia in the orofacial area under normal conditions. However, intracisternal administration of bicuculline (50 ng) produced a paradoxical anti-allodynic effect under inflammatory pain conditions. Pretreatment with resiniferatoxin (RTX), which depletes capsaicin receptor protein in primary afferent fibers, did not alter the paradoxical anti-allodynic effects produced by the intracisternal injection of bicuculline. Intracisternal injection of bumetanide, an Na-K-Cl cotransporter (NKCC 1) inhibitor, reversed the $IL-1{\beta}$-induced mechanical allodynia. In the control group, application of GABA ($100{\mu}M$) or muscimol ($3{\mu}M$) led to membrane hyperpolarization in gramicidin perforated current clamp mode. However, in some neurons, application of GABA or muscimol led to membrane depolarization in the $IL-1{\beta}$-treated rats. These results suggest that some large myelinated $A{\beta}$ fibers gain access to the nociceptive system and elicit pain sensation via $GABA_A$ receptors under inflammatory pain conditions.

• Korean Journal of Plant Resources
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• v.19 no.6
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• pp.660-664
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• 2006

The aerial part of Siegesbeckia pubescens (Compositae) has been used to treat rheumatoid arthritis and hypertension in the Oriental medicine. This crude drug has been used without process (SP-0) or with three times-process of steaming and drying (SP-3) or the nine times of that process (SP-9). To search for the antinociceptive anti-inflammatory components from this crude drug, activity-directed fractionation was performed on this crude drug. Since the $CHCl_3$ extract was shown to have a more potent effect than other extracts, it was subjected to silica gel & ODS column chromatography to yield two diterpene compounds (1). Compound 1 was structurally identified as ent-16 (H, 17-hydroxykauran-19-oic acid, which were tentatively named siegeskaurolic acid A. A main diterpene, siegeskaurolic acid A was tested for the antiiflammatory antinociceptive effects using both hot plate- and writhing anti-nociceptive assays and carrageenan-induced anti-inflammatory assays in mice and rats. Pretreatment with siegeskaurolic acid A (20 and 30mg/kg) significantly reduced the stretching episodes, action time of mice and carrageenan-induced edema. These results support that siegeskaurolic acid is a main diterpene responsible for antinociceptive and antiiflammatory action of S. pubescens. In addition, the assays on SP-0, SP-3 and SP-9 produced the experimental results that SP-9 had more significant effects than other two crude drugs. These results suggest that the processing on the original plant may lead to the higher pharmacological effect.

• The Journal of Korean Medicine
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• v.28 no.4
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• pp.124-135
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• 2007

Backgrounds : Scutellaria baicalensis has been used as a medicinal plant to treat various disease conditions accompanying inflammatory response and oxidative stress. Objectives : The aim of this study is to evaluate the effects of Scutellaria baicalensis against inflammatory, pain and edema Methods : In vitro, the effects of Scutellaria baicalensis against lipopolysaccharide-induced inflammation were investigated in mouse BV2 microglial cells. In vivo, the effects of Scutellaria baicalensis on acetic acid-induced writhing response, carrageenan-induced edema and the plantar test (nociceptive thermal stimulation) were investigated using rats and mice. Results : The present results showed that pre-treatment with the aqueous extract of Scutellaria baicalensis suppressed the lipopolysaccharide-stimulated cyclooxygenase-2 expressions in mouse BV2 microglial cells. The aqueous extract of Scutellaria baicalensis inhibited acetic acid-induced abdominal pain in mice and also reduced thermal pain in rats. However, no significant inhibition on carrageenan-induced edema in rats. Conclusions : The present study showed that Scutellaria baicalensis possesses anti-inflammatory and analgesic effects.

• Journal of Dental Anesthesia and Pain Medicine
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• v.22 no.2
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• pp.97-105
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• 2022

Background: The pentadecapeptide BPC-157 has been shown to have anti-inflammatory and wound healing effects on multiple target tissues and organs. Peptides have potent anti-inflammatory effects on periodontal tissues in rats with periodontitis. Few studies have investigated the effect of BPC-157 on pain after dental procedures or oral surgeries. The purpose of the present study was to investigate the antinociceptive effects of BPC-157 on postoperative incisional pain in rats. Methods: Sprague-Dawley rats were randomly divided into five groups: control (saline with the same volume), BPC10 (10 ㎍/kg of BPC-157), BPC20 (20 ㎍/kg of BPC-157), BPC40 (40 ㎍/kg of BPC-157), and morphine (5 mg/kg of morphine). A 1-cm longitudinal incision was made through the skin, fascia, and muscle of the plantar aspect of the hind paw in isoflurane-anesthetised rats. Withdrawal responses were measured using von Frey filaments at 0, 2, 6 h and 4, 7 d after incision. The formalin test was also performed to differentiate its anti-nociceptive effect from an inflammatory reaction or central sensitization. Pain behavior was quantified periodically in phases 1 and 2 by counting the number of flinches in the ipsilateral paw after injection with 30 µL of 5% formalin. Results: The threshold of mechanical allodynia was significantly increased in the BPC10, BPC20, BPC40 and morphine groups compared with that in the control group at 2 h. These increasing thresholds then returned to the levels of the control group. The BPC-157 group showed a much higher threshold at 4 days after incision than the control group. The thresholds of the BPC groups, except the morphine group, were normalized 7 days after incision. The flinching numbers of the BPC10, BPC20, BPC40 and morphine groups were significantly decreased in phase 1, but there was no decrease in the BPC-157 groups except the morphine group in phase 2. Conclusions: BPC-157 was effective only for a short period after incision. It was also effective during phase 1 but not during phase 2, as determined by the formalin test. BPC-157 might have a short antinociceptive effect, even though it has anti-inflammatory and wound healing effects.

• The Korean Journal of Pain
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• v.35 no.2
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• pp.173-182
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• 2022

Background: Neurokinin-1 (NK1) and calcitonin gene-related peptide (CGRP) play a vital role in pain pathogenesis, and these proteins' antagonists have attracted attention as promising pharmaceutical candidates. The authors investigated the anti-nociceptive effect of co-administration of the CGRP antagonist and an NK1 antagonist on pain models compared to conventional single regimens. Methods: C57Bl/6J mice underwent sciatic nerve ligation for the neuropathic pain model and were injected with 4% formalin into the hind paw for the inflammatory pain model. Each model was divided into four groups: vehicle, NK1 antagonist, CGRP antagonist, and combination treatment groups. The NK1 antagonist aprepitant (BIBN4096, 1 mg/kg) or the CGRP antagonist olcegepant (MK-0869, 10 mg/kg) was injected intraperitoneally. Mechanical allodynia, thermal hypersensitivity, and anxiety-related behaviors were assessed using the von Frey, hot plate, and elevated plus-maze tests. The flinching and licking responses were also evaluated after formalin injection. Results: Co-administration of aprepitant and olcegepant more significantly alleviated pain behaviors than administration of single agents or vehicle, increasing the mechanical threshold and improving the response latency. Anxiety-related behaviors were also markedly improved after dual treatment compared with either naive mice or the neuropathic pain model in the dual treatment group. Flinching frequency and licking response after formalin injection decreased significantly in the dual treatment group. Isobolographic analysis showed a meaningful additive effect between the two compounds. Conclusions: A combination pharmacological therapy comprised of multiple neuropeptide antagonists could be a more effective therapeutic strategy for alleviating neuropathic or inflammatory pain.

• Journal of the Korean Academy of Clinical Electrophysiology
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• v.5 no.1
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• pp.45-58
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• 2007

This study aims to examine the effects on nociceptive neuron excitability by application of electroacupuncture and Meloxicam gel in rat with inflammation. It used 24 rats for experiment, divided them into control group, electroacupuncture group(EA group), Meloxicam group(ME group), combination of electroacupuncture with Meloxicam group(EA+ME group), caused hyperalgesia by injecting ${\lambda}$-carrageenan into hindpaw and conducted treatment three times for experimental period. Noxious flexion withdrawal reflex(NFR) and somatosensory evoked potential(SEP) were measured immediately after induction, at 24 hours, 48 hours and 72 hours after induction. Change of NFR(reaction time, RMS) showed no significant differences among EA group, Meloxicam group, and EA+Meloxicam group, but all treatment groups showed significant differences compared to control group from 48 hours. In NFR threshold, there were significant differences between EA+Meloxicam and other groups. In SEP amplitude, there were significant differences between EA+Meloxicam and control group from 48 hours. This study showed that EA+Meloxicam gel had an effect on nociceptive neurone excitability. Therefore, it is considered that appropriate combination of anti-inflammatory drug with electroacupuncture for pain control will be very desirable.

• Journal of Acupuncture Research
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• v.26 no.6
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• pp.91-100
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• 2009

Objectives : The objective of this study is to investigate Anti-nociceptive and anti-inflammatory effects of Clematidis Radix (CR) herbal-acupuncture on the test rats with induced acute pain. Methods : The effects of Clematidis Radix (CR)-distillates were investigated in three types of models with three different pain. Highly purified distillate of CR called CR herbal-acupuncture was injected to Zusanli ($ST_{36}$) acupoint. In the tail flick test, the CR herbal-acupuncture treatment did not show a significant effect of relieving acute pain. To investigate the anti-inflammatory effect of CR herbal-acupuncture, the second testing model'pain was induced by injecting formalin to its planter. For the last model, carrageenan was injected into tarsal joint. the medicinal effect of CR herbal-acupuncture was evaluated through the behavioral analyses such as licking time, weight distribution ratio and ankle circumference. Results : In the formalin test, the analgesic effect of CR herbal-acupuncture was more pronounced in the late phase (for 20 min after the early phase) than in the early phase (for the first 10 min post formalin injection). It was proven by weight distribution ratio testing and ankle edema testing that herbal-acupuncture of CR inhibited arthritis caused by the carrageenan. Conclusions : These results revealed that CR herbal-acupuncture was effective to alleviate the inflammatory pain and could be used as an analgesic treatment with an anti-inflammatory effect.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.6
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• pp.359-364
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• 2010

Many therapeutic roles have been proposed for sigma-1 receptor (Sig-1R), but the involvement of Sig-1R in neuropathic pain has currently not been well explored. The present study aimed to evaluate the anti-nociceptive effect of Sig-1R antagonist (BD1047) in a rat model of chronic compression of the dorsal root ganglion (CCD), which is a model of human foraminal stenosis and radicular pain. When stainless steel rods were inserted into the intervertebral foramen of lumbar vertebrae 4 and 5, the CCD developed reliable mechanical (from 3 day) and cold allodynia (from 1 day) as compared with the sham operation group. The spinal expressions of Sig-1R and phosphorylation of extracellular signal-regulated kinase (pERK) were significantly increased from day 3 to day 14 after CCD surgery, as is consistent with the manifestation of allodynia. The BD 1047 (10, 30, 100 mg/kg) administered on postoperative days 0~5 dose-dependently suppressed both the induction of allodynia and the elevation of the spinal pERK expression in a manner comparable with that of gabapentin (100 mg/kg). At 7 days post-CCD surgery, BD1047 (10, 30, 100 mg/kg) administration also produced anti-nociceptive effects on the mechanical and cold allodynia similar with those of gabapentin (100 mg/kg). Therefore, this data suggested that Sig-1R may play an important role in both the development and maintenance of CCD-induced neuropathy.