• Clinical and Experimental Pediatrics
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• v.46 no.7
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• pp.695-701
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• 2003

Purpose : It had been suggested that pain arising from deep somatic body regions influences neural activity within periaqueductal gray(PAG) of midbrain via distinct spinal pathways. Aspirin is one of the popular non-steroidal anti-inflammatory drugs used in the management of pain. Fos expression was used as a marker for neuronal activity throughout central neurons following painful peripheral stimulation. This study was prepared to investigate changes of c-Fos immunoreactivity in midbrain by deep pain and effects of aspirin. Methods : Male Sprague-Dawley rats were injected with 0.1 mL of 5% formalin in the plantar muscle of the right hindpaw. For experimental group II, aspirin was injected intravenously before injection of formalin. An aspirin-untreated group was utilized as group I. Rats were sacrificed at 0.5, 1, 2, 6 and 24 hours after formalin injection. Rat's brains were removed and sliced in rat brain matrix. Brain slices were coronally sectioned at interaural 1.00-1.36 mm. Serial sections were immunohistochemically reacted with polyclonal c-Fos antibody. The numbers of c-Fos protein immunoreactive neurons in ventrolateral periaqueductal gray(VLPAG) and dorsomedial periaqueductal gray(DMPAG) were counted and analyzed statistically with Mann-Whitney U tests. Results : Higher numbers of c-Fos protein immunoreactive neurons were found in VLPAG. In both VLPAG and DMPAG of formalin-treated group, the numbers of c-Fos protein immunoreactive neurons were significantly higher at all time points than the formalin-untreated group, which peaked at two hours. The numbers of c-Fos immunoreactive neuron of the aspirin-treated group were less compared to the aspirin-untreated group at each time point. Conclusion : These results provide some basic knowledge in understanding the mechanism of formalin-induced deep somatic pain and the effects of aspirin.

• Journal of dental hygiene science
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• v.15 no.6
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• pp.800-806
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• 2015

The aim of this study was to investigate whether intracisternal administrations of triptolide and N-nitro-L-arginine Methyl Ester (L-NAME) are involved in the regulation of temporomandibular joint (TMJ) pain. The TMJ pain was induced by the injection of 5% formalin ($30{\mu}l$) into TMJ capsule of rats. The pain behavioral responses was recorded the number of grooming or scratching on the left TMJ area for 9 successive 5 minutes intervals. Triptolide and L-NAME were administrated intracisternally 10 minutes before formalin injection. The intra-articular injection of formalin produced a biphasic pattern of pain response (first phase: 0~10 minutes and second phase: 11~45 minutes). The intracisternal administration of triptolide ($1{\mu}g/10{\mu}l$) and L-NAME ($0.1{\mu}g/10{\mu}l$) suppressed the TMJ pain behavior in each experiment. Co-administration of two drugs was shown the enhanced effect than the analgesic effect by single-administration of triptolide ($1{\mu}g/10{\mu}l$). The triptolide could be a useful analgesic agent for the treatment of TMJ pain, and it is expected to reduce the substantial amount of it via co-administration of synthetic chemical compound and natural products.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.3
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• pp.207-216
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• 2021

Several studies have previously reported that exposure to stress provokes behavioral changes, including antinociception, in rodents. In the present study, we studied the effect of acute cold-water (4℃) swimming stress (CWSS) on nociception and the possible changes in several signal molecules in male ICR mice. Here, we show that 3 min of CWSS was sufficient to produce antinociception in tail-flick, hot-plate, von-Frey, writhing, and formalin-induced pain models. Significantly, CWSS strongly reduced nociceptive behavior in the first phase, but not in the second phase, of the formalin-induced pain model. We further examined some signal molecules' expressions in the dorsal root ganglia (DRG) and spinal cord to delineate the possible molecular mechanism involved in the antinociceptive effect under CWSS. CWSS reduced p-ERK, p-AMPKα1, p-AMPKα2, p-Tyk2, and p-STAT3 expression both in the spinal cord and DRG. However, the phosphorylation of mTOR was activated after CWSS in the spinal cord and DRG. Moreover, p-JNK and p-CREB activation were significantly increased by CWSS in the spinal cord, whereas CWSS alleviated JNK and CREB phosphorylation levels in DRG. Our results suggest that the antinociception induced by CWSS may be mediated by several molecules, such as ERK, JNK, CREB, AMPKα1, AMPKα2, mTOR, Tyk2, and STAT3 located in the spinal cord and DRG.

• The Korean Journal of Pain
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• v.27 no.3
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• pp.246-252
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• 2014

Background: Neuropathic pain is generally defined as a chronic pain state resulting from peripheral and/or central nerve injury. There is a lack of effective treatment for neuropathic pain, which may possibly be related to poor understanding of pathological mechanisms at the molecular level. Curcumin, a therapeutic herbal extract, has shown to be effectively capable of reducing chronic pain induced by peripheral administration of inflammatory agents such as formalin. In this study, we aimed to show the effect of curcumin on pain behavior and serum COX-2 level in a Chronic Constriction Injury (CCI) model of neuropathic pain. Methods: Wistar male rats (150-200 g, n = 8) were divided into three groups: CCI vehicle-treated, sham-operated, and CCI drug-treated group. Curcumin (12.5, 25, 50 mg/kg, IP) was injected 24 h before surgery and continued daily for 7 days post-surgery. Behavioral tests were performed once before and following the days 1, 3, 5, 7 after surgery. The serum COX-2 level was measured on day 7 after the surgery. Results: Curcumin (50 mg/kg) decreased mechanical and cold allodynia (P < 0.001) and produced a decline in serum COX-2 level (P < 0.001). Conclusions: A considerable decline in pain behavior and serum COX-2 levels was seen in rat following administration of curcumin in CCI model of neuropathic pain. High concentration of Curcumin was able to reduce the chronic neuropathic pain induced by CCI model and the serum level of COX-2.

• Korean Journal of Pharmacognosy
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• v.44 no.1
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• pp.70-74
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• 2013

Ligularia stenocephala has been widely used as a traditional medicine for the treatment of lots of diseases such as asthma, arthritis, and jaundice. In this study, we evaluated the anti-nocicepitve activities of methanolic extract of L. stenocephala (MLS) using various pain models including thermal nociception as well as chemical nociception methods. MLS showed significant increase in latency time in the tail immersion test and hot-plate test. In addition, the number of acetic acid-induced abdominal constrictions was decreased by MLS. MLS also attenuated paw licking time in the formalin test. The combination test using naloxone revealed that the anti-nociceptive properties of MLS was not associated with opioid receptor activation. The present results demonstrate that MLS may possibly used as valuable analgesic agent for the treatment of nociceptive pain.

• Journal of dental hygiene science
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• v.15 no.4
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• pp.424-429
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• 2015

The aim of this study was to investigate whether peripheral or central administration of triptolide is involved in pain modulation in inflammatory orofacial pain. The inflammatory orofacial pain was induced by the injection of 5% formalin into right vibrissa pad of rats. The pain behavioral response was measured the number of grooming or scratching on the orofacial area for 9 successive 5 minutes intervals. Triptolide was administrated into the identified vibrissa pad (12.5, 25, $50{\mu}g/50{\mu}l$) or intracisternal space (0.01, 0.1, $1{\mu}g/10{\mu}l$) 10 min before formalin injection. The nociceptive responses were reduced in the 2nd phase (11~45 minutes), particularly 20, 30 minutes after fomalin injection following administration of triptolide into vibrissa pad (25, $50{\mu}g/50{\mu}l$). Intracisternal ($1{\mu}g/10{\mu}l$) administration of triptolide alleviated the formalin-induced pain behaviors in the 2nd phase, especially 25~40 minutes after formalin injection. Triptolide could be a promising analgesic agent in the treatment of inflammatory orofacial pain.

• Natural Product Sciences
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• v.17 no.4
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• pp.303-308
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• 2011

Spirodela polyrrhiza L. Schleid. (Lemnaceae), also known as 'duckweed', is a traditional medicine in Korea. The whole plant is used to treat many diseases, including the common cold, edema, acute nephritis, and urticaria. The present study investigated antinociceptive properties of the EtOAc soluble fraction of S. polyrrhiza (ESP). The antinociceptive activities of ESP were studied using experimental models of pain, including thermal nociception methods, such as the tail immersion test and the hotplate test. Moreover, we studied chemical nociception induced by intraperitoneal acetic acid and subplantar formalin in mice. ESP exhibited dose-dependent antinociceptive activity in both thermal and chemical pain models. In a drug combination test using the opioid receptor antagonist naloxone, diminished analgesic activities of ESP were observed, indicating that the antinociceptive activity of ESP is mediated by opioid receptors.

• Biomolecules & Therapeutics
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• v.24 no.4
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• pp.418-425
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• 2016

We measured anti-nociceptive activity of prim-o-glucosylcimifugin (POG), a molecule from Saposhnikovia divaricate (Turcz) Schischk. Anti-nociceptive or anti-inflammatory effects of POG on a formalin-induced tonic nociceptive response and a complete Freund's adjuvant (CFA) inoculation-induced rat arthritis pain model were studied. Single subcutaneous injections of POG produced potent anti-nociception in both models that was comparable to indomethacin analgesia. Anti-nociceptive activity of POG was dose-dependent, maximally reducing pain 56.6% with an $ED_{50}$ of 1.6 mg. Rats given POG over time did not develop tolerance. POG also time-dependently reduced serum TNF${\alpha}$, IL-$1{\beta}$ and IL-6 in arthritic rats and both POG and indomethacin reduced spinal prostaglandin E2 ($PGE_2$). Like indomethacin which inhibits cyclooxygenase-2 (COX-2) activity, POG dose-dependently decreased spinal COX-2 content in arthritic rats. Additionally, POG, and its metabolite cimifugin, downregulated COX-2 expression in vitro. Thus, POG produced potent anti-nociception by downregulating spinal COX-2 expression.

• The Korean Journal of Pain
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• v.9 no.2
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• pp.311-317
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• 1996

Background: Following peripheral nerve injury, rats will show a tactile allodynia and hyperalgesia. But the mechanism of allodynia is still obscure. Previous studies have shown this allodynia was reversed by intrathecal alpha-2 agonists and NMDA antagonists, but not by morphine. In formalin test, either the pretreatment of NMDA antagonist or morphine prevents the hyperalgesia. The present studies, using rats rendered allodynic by ligation of the left L5 and L6 nerves, aimed to investigate the effects of pretreatment of MK-801 and morphine on the development of tactile allodynia. Methods and Material: Male Sprague-Dawley rats (100~150g) were anesthetized with halothane, the left L5 and L6 spinal nerves were ligated tightly by 6-0 black silk. For sham operation muscle dissection was performed but the spinal nerve was not ligated. For pretreatment of drugs, MK-801 (NMDA antagonist; 0.3 mg/kg). CNQX (non-NMDA) antagonist; 0.3 mg/kg), morphine (1 mg/kg) or saline (placebo) was administered subcutaneously 30 minutes before operation. A second dose was administered subcutaneously 24 hours after operation and further doses were given daily for 2 days further. The volume of injection was 5 ml/kg. To assess the mechanical allodynia, paw withdrawal thresholds of ipsilateral limb were determined using 8 von Frey hairs. Results: Within 2 days saline, CNQX or morphine injected rats developed tactile allodynia (paw withdrawal threshold was about 2g), and persisted for over 2 weeks. Pretreatment of MK-801 delayed the development of tactile allodynia for 3 days comparing to that of saline injected rat. Conclusion: NMDA receptor in the central nerve system plays an important role in the development of tactile allodynia induced by peripheral nerve injury. But the mechanism may be different from hyperalgesia developed in formalin test.

• Natural Product Sciences
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• v.19 no.4
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• pp.311-315
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• 2013

Ribes fasciculatum (Saxifragaceae) has been widely used as a traditional medicine for the treatment of cough, antidote, cold, lacquer poison, and sore throat. In the present study, we evaluated the anti-nociceptive effects of ethyl acetate fraction of Ribes fasciculatum (ERF) in mice. Test results of tail-immersion test and hot plate test revealed that the ERF had strong anti-nociceptive activities on thermal nociception in a dose dependent manner, indicating ERF's anti-nociception on the central pain. Moreover, the acetic acid-induced chemical nociception was also significantly reduced by ERF treatment. This result shows that ERF may also work on the peripheral pain. We further performed formalin test to confirm ERF's anti-nociceptive properties and found that pain responses were significantly decreased by ERF treatment. Interestingly, in the combination test with naloxone, the analgesic activity of ERF was not changed, indicating that the opioid receptor was not involved in the ERF-mediated anti-nociception. These results indicate that ERF might be possibly used as a painkiller for the treatment of nociceptive pains.