• The Korean Journal of Physiology and Pharmacology
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• 제21권1호
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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.

• Journal of Acupuncture Research
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• 제20권4호
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• pp.11-23
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• 2003

Objective: In this study, the analgesic effect of gold injection aqua-acupuncture on CFA induced arthritis in rats was inverstigated. Furthermore, to determine the antinociceptive mechanism of gold injection aqua-acupuncture, naloxone and yohimbine were administrated intraperitoneally 15min prior to the gold injection aqua-acupuncture. Methods: The experimental groups were divided into 6 groups. Control group, NSI, AMI, AMI+SL : AMI+Nx, AMI+Yb. Thereafter we measured the chages of TFL between control and experimental groups. Results: 1. The tail flick latency induced by CFA was significantly increased on AMI as compared with the NSI group. 2. Effect of sodium aurothiomalate aqua-acupuncture in TFL on CFA was decreased after application of naloxone. The anti-nociceptive effect of AMI was completely antagonized by naloxone(an opioid receptor antagonist). 3. Effect of sodium aurothiomalate aqua-acupuncture in TFL on CFA was decreased after application of yohimbine. The anti-nociceptive effect of AMI was completely antagonized by yohimbine(${\alpha}2$-adrenoceptor antagonist). Conclusions: According to the results, gold injection aqua-acupuncture has significant analgesic effects on adjuvant induced arthritis in rats and the effect of anti-nociception was mediated by opiodergic system and ${\alpha}2$-adrenergic system.

• 약학회지
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• 제51권6호
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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.

• 대한한의학회지
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• 제28권4호
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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.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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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)

• 대한임상전기생리학회지
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• 제5권1호
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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.

• 한국식생활문화학회지
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• 제39권1호
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• pp.74-81
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• 2024

Ulcerative colitis (UC) is a chronic inflammatory intestinal disease characterized by an imbalance in immune function and the overexpression of inflammatory cytokines and mediators. Vitamin B2, also known as riboflavin (Libof), is an essential water-soluble vitamin with numerous beneficial properties, including antioxidant, anti-aging, anti-inflammatory, anti-nociceptive, and anti-cancer effects. In this study, we aimed to investigate the protective effects of Libof on dextran sulfate sodium (DSS)-induced experimental colitis. The C57BL/6 mice were used as the in vivo model of chronic colitis to investigate the anti-inflammatory effects of Libof. RAW 264.7 cells were used for the in vitro investigation of the molecular mechanisms underlying these effects. In vivo, Libof alleviated the DSS-induced disease activity index (DAI), colon length shortening, and colonic pathological damage. In vitro, Libof inhibited lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 production in RAW 264.7 cells. Moreover, Libof inhibited LPS-induced nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression in RAW 264.7 cells. In conclusion, these findings indicate that Libof shows potential as an agent for the treatment of UC.

• The Korean Journal of Physiology and Pharmacology
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• 제14권6호
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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.

• Biomolecules & Therapeutics
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• 제25권3호
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• pp.259-265
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• 2017

This study aimed to investigate the analgesic effect of substance P (SP) in an animal model of neuropathic pain. An experimental model of neuropathic pain, the chronic constriction injury (CCI) model, was established using ICR mice. An intravenous (i.v.) injection of SP (1 nmole/kg) was administered to the mice to examine the analgesic effects of systemic SP on neuropathic pain. Behavioral testing and immunostaining was performed following treatment of the CCI model with SP. SP attenuated mechanical allodynia in a time-dependent manner, beginning at 1 h following administration, peaking at 1 day post-injection, and decaying by 3 days post-injection. The second injection of SP also increased the threshold of mechanical allodynia, with the effects peaking on day 1 and decaying by day 3. A reduction in phospho-ERK and glial fibrillary acidic protein (GFAP) accompanied the attenuation of mechanical allodynia. We have shown for the first time that i.v. administration of substance P attenuated mechanical allodynia in the maintenance phase of neuropathic pain using von Frey's test, and simultaneously reduced levels of phospho-ERK and GFAP, which are representative biochemical markers of neuropathic pain. Importantly, glial cells in the dorsal horn of the spinal cord (L4-L5) of SP-treated CCI mice, expressed the anti-inflammatory cytokine, IL-10, which was not seen in vehicle saline-treated mice. Thus, i.v. administration of substance P may be beneficial for improving the treatment of patients with neuropathic pain, since it decreases the activity of nociceptive factors and increases the expression of anti-nociceptive factors.

• The Korean Journal of Pain
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• 제35권2호
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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.