• The Korean Journal of Pain
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• v.32 no.3
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• pp.160-167
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• 2019

Background: Pain is a complex mechanism which involves different systems, including the opioidergic and GABAergic systems. Due to the side effects of chemical analgesic agents, attention toward natural agents have been increased. Artemisinin is an herbal compound with widespread modern and traditional therapeutic indications, which its interaction with the GABAergic system and antinoniceptive effects on neuropathic pain have shown. Therefore, this study was designed to evaluate the antinociceptive effects of artemisinin during inflammatory pain and interaction with the GABAergic and opioidergic systems by using a writhing response test. Methods: On the whole, 198 adult male albino mice were used in 4 experiments, including 9 groups (n = 6) each with three replicates, by intraperitoneal (i.p.) administration of artemisinin (2.5, 5, and 10 mg/kg), naloxone (2 mg/kg), bicuculline (2 mg/kg), saclofen (2 mg/kg), indomethacin (5 mg/kg), and ethanol (10 mL/kg). Writhing test responses were induced by i.p. injection of 10 mL/kg of 0.6% acetic acid, and the percentage of writhing inhibition was recorded. Results: Results showed significant dose dependent anti-nociceptive effects from artemisinin which, at a 10 mg/kg dose, was statistically similar to indomethacin. Neither saclofen nor naloxone had antinociceptive effects and did not antagonize antinociceptive effects of artemisinin, whereas bicuculline significantly inhibited the antinocicptive effect of artemisinin. Conclusions: It seems that antinocicptive effects of artemisinin are mediated by $GABA_A$ receptors.

• 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 Pain
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• v.13 no.1
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• pp.38-43
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• 2000

Background: Preemptive analgesia may decrease postoperative pain by preventing nociceptive inputs generated during surgery. The preemptive effect of intravenous nalbuphine was examined in gynecological surgery. Methods: Forty female patients scheduled for gynecological surgery were randomly allocated into two groups. Each patient received 10 mg of intravenous nalbuphine as a bolus dose at the closure of peritoneum in group I (n=20) and before the skin incision in group II (n=20). After the bolus dose, the intravenous patient controlled analgesia (IV-PCA) which contained 50 mg of nalbuphine, 120 mg of ketorolac, 0.25 mg of droperidol and 90 ml of 5% dextrose water was given continuously at the rate of 2 ml/min. The postoperative visual analogue scale pain score (VAS), the total amount of the analgesics used, the degree of satisfaction of the patients and the developement of side effects were examined for 2 days. Results: VAS were significantly lower in group II than in group I after 9 and 12 hours. The cumulative consumption of analgesics in group II was significantly less than in group I. Most patients were satisfied with this regimen. There were no remarkable side effects. Conclusions: Preemptive analgesia with intravenous nalbuphine decreased postoperative pain and analgesic requirement. The analgesic effect of IV-PCA with nalbuphine-ketorolac was effective in control of postoperative pain in gynecologic surgery.

• International Journal of Oral Biology
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• v.37 no.3
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• pp.121-129
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• 2012

Previous clinical studies have demonstrated that gabapentin, a drug that binds to the voltage-gated calcium channel ${\alpha}2{\delta}1$ subunit proteins, is effective in the management of neuropathic pain, but there is limited evidence that addresses the participation of glial cells in the antiallodynic effects of this drug. The present study investigated the participation of glial cells in the anti-nociceptive effects of gabapentin in rats with trigeminal neuropathic pain produced by mal-positioned dental implants. Under anesthesia, the left mandibular second molar was extracted and replaced by a miniature dental implant to induce injury to the inferior alveolar nerve. Mal-positioned dental implants significantly decreased the air-puff thresholds both ipsilateral and contralateral to the injury site. Gabapentin was administered intracisternally beginning on postoperative day (POD) 1 or on POD 7 for three days. Early or late treatment with 0.3, 3, or 30 ${\mu}g$ of gabapentin produced significant anti-allodynic effect in the rats with mal-positioned dental implants. On POD 9, in the mal-positioned dental implants group, OX-42, a microglia marker, and GFAP, an astrocyte marker, were found to be up-regulated in the medullary dorsal horn, compared with the naive group. However, the intracisternal administration of gabapentin (30 ${\mu}g$) failed to reduce the number of activated microglia or astrocytes in the medullary dorsal horn. These findings suggest that gabapentin produces significant antinociceptive effects, which are not mediated by the inhibition of glial cell function in the medullary dorsal horn, in a rat model of trigeminal neuropathic pain.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.15 no.9
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• pp.5594-5601
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• 2014

The aim of this study was to evaluate the analgesic effects of Samultang by measuring the anti-inflammatory and antioxidative activities in formalin-induced orofacial pain. The anti-inflammatory and anti-oxidative effects were measured by western blot analysis for p38 MAPK(Mitogen-activated protein kinases), iNOS(induceble nitric oxide synthase) and NOX4(nicotinamide adenine dinucleotide phosphate4) in a rat's brain and medulla oblongata. Samultang significantly attenuated the increased formalin-induced nociceptive response and inhibited the p38 MAPK and iNOS that led to inflammatory pain. In addition, this study indicated that Samultang possess antioxidative effects through the blockade of NOX4. These findings suggest that Samultang plays an important role in the peripheral processing of inflammatory pain in the orofacial area.

• Journal of Veterinary Science
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• v.22 no.1
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• pp.9.1-9.11
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• 2021

Background: Scalding burn injuries can occur in everyday life but occur more frequently in young children. Therefore, it is important to develop more effective burn treatments. Objectives: This study examined the effects of bee venom (BV) stimulation on scalding burn injury-induced nociception in mice as a new treatment for burn pain. Methods: To develop a burn injury model, the right hind paw was immersed temporarily in hot water (65℃, 3 seconds). Immediately after the burn, BV (0.01, 0.02, or 0.1 mg/kg) was injected subcutaneously into the ipsilateral knee area once daily for 14 days. A von Frey test was performed to assess the nociceptive response, and the altered walking parameters were evaluated using an automated gait analysis system. In addition, the peripheral and central expression changes in substance P (Sub P) were measured in the dorsal root ganglion and spinal cord by immunofluorescence. Results: Repeated BV treatment at the 2 higher doses used in this study (0.02 and 0.1 mg/kg) alleviated the pain responses remarkably and recovered the gait performances to the level of acetaminophen (200 mg/kg, intraperitoneal, once daily), which used as the positive control group. Moreover, BV stimulation had an inhibitory effect on the increased expression of Sub P in the peripheral and central nervous systems by a burn injury. Conclusions: These results suggest that a peripheral BV treatment may have positive potency in treating burn-induced pain.

• Korean Journal of Plant Resources
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• v.23 no.6
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• pp.513-518
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• 2010

In the present study, the antinociceptive profiles of Dianthus chinensis L extract were examined in ICR mice. Dianthus chinensis L extract administered orally (200 mg/kg) showed an antinociceptive effect as measured by the tail-flick and hot-plate tests. In addition, Dianthus chinensis L extract attenuated the writhing numbers in the acetic acid-induced writhing test. Furthermore, the cumulative nociceptive response time for intrathecal (i.t.) injection of substance P ($0.7\;{\mu}g$) was diminished by Dianthus chinensis L extract. Intraperitoneal (i.p.) pretreatment with yohimbine ($\alpha_2$-adrenergic receptor antagonist) attenuated antinociceptive effect induced by Dianthus chinensis L extract in the writhing test. However, naloxone (opioid receptor antagonist) or methysergide (5-HT serotonergic receptor antagonist) did not affect antinociception induced by Dianthus chinensis L extract in the writhing test. Our results suggest that Dianthus chinensis L extract shows an antinociceptive property in various pain models. Furthermore, this antinociceptive effect of Dianthus chinensis L extract may be mediated by $\alpha_2$-adrenergic receptor, but not opioidergic and serotonergic receptors.

• Natural Product Sciences
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• v.7 no.3
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• pp.76-82
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• 2001

The pharmacological activities of the acetonitrile (MeCN), hexane extracts and isolated pure terpenoidal compound Lupeol from the leaves of Teclea nobilis, Delile (TN), on inflammation induced by carrageenan an implantation of cotton pellets in rats; the nociceptive response using writhing and tail flick tests and the antipyretic activity in yeast-induced fever were examined in mice. Oral administration of TN extracts at doses of 150 and 300 mg/ks and lupeol 5 and 10 mg/kg showed a significant anti-inflammatory activity in rats. The extracts of TN and lupeol significantly decreased the number of contractions and stretchings induced by acetic acid and heat-induced pain in mice. The antipyretic effect of extracts and lupeol was also found to be significant. The behavioral observation of animals showed that the hexane extract and lupeol caused CNS depressant activity and did not produce any toxic or lethal effects in animals at various dose levels. The results suggest that the Teclea nobilis extracts and lupeol possesses anti-inflammatory, analgesic and antipyretic activities.

• The Korean Journal of Pain
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• v.18 no.2
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• pp.133-137
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• 2005

Background: Cannabinoids have shown antinociceptive action. The aims of this study were to examine the effect of chronic infusion of a cannabinoids receptors agonist (WIN 55,212-2) for thermal nociception at the spinal level, and to also observe the development of toxicity. Methods: Male Sprague-Dawley rats were implanted with lumbar intrathecal catheters with the nociceptive response (withdrawal response latency) determined by exposing the plantar surface of the hindpaw to radiant heat. Initially, the effect of intrathecal WIN 55,212-2 was evaluated followed by the change in the effect at 1, 2, 3 and 4 weeks after repeated infusion. Finally, the histopathological findings were assessed 1 and 4 weeks following the infusion of WIN 55,212-2. Results: Intrathecal WIN 55,212-2 was found to produce a limited antinociception during the thermal test. %MPE of WIN 55,212-2 at 1, 2, 3, and 4 weeks after infusion was not different from each other. No abnormal pathological findings were observed following a chronic intrathecal infusion of WIN 55,212-2. Conclusions: WIN 55,212-2, a cannabinoids receptors agonist, may be useful in the management of thermal nociception, without changing the effectiveness or causing the toxicity following a chronic infusion at the spinal level.

• The Korean Journal of Pain
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• v.14 no.2
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• pp.225-230
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• 2001

Background: Opioids such as morphine are widely used in the treatment for pain, but chronic treatment with morphine can be complicated by the development of tolerance. The mechnisms of tolerance were still not completely understood, but recently it has been reported that NOS inhibitors can prevent development of morphine tolerance in animals. The present study accessed the possible role of supraspinal NO on antinociceptive effect of morphine in morphine tolerance using a highly specific inhibitor of the neuronal isoform of NOS, 1-(2-trifluoromethylphenyl) imidazole (TRIM). Methods: Thirty two male SD rats (300 g) were prepared with intracerebroventricular (icv) and IV cannulae. We administrated IV morphine, 3 mg/kg, daily for 4 days, resulting in tolerance. On the fifth day, a challenge dose of morphine, 3 mg/kg, was administered following pretreatment with icv TRIM, $10{\mu}g$. We also evaluated the antinociceptive effect of icv TRIM alone and the effect on a single dose of morphine (3 mg/kg) in morphine nave rats. Antinociception from morphine was determined by response to intraplantar injection of 5% formalin $100{\mu}l$ was qualified as the number of flinches in the first 0-10 min (first phase), 10-40 min Phase IIa, and 40-60 min (Phase IIb). Results: Pretreatment with icv TRIM significantly enhanced the antinociceptive effects of systemically administered morphine in morphine tolerant rats. The antinociceptive effect of morphine in opioid nave rats was also significantly increased by pretreatment with icv TRIM. Conclusions: Our results further support the hypothesis that supraspinal NO modulates morphine-sensitive nociceptive process in morphine tolerance due to chronic intravenous administration.