• The Korean Journal of Physiology and Pharmacology
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• v.21 no.6
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• pp.657-666
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• 2017

Paclitaxel, a chemotherapeutic drug, induces severe peripheral neuropathy. Gabapentin (GBT) is a first line agent used to treat neuropathic pain, and its effect is mediated by spinal noradrenergic and muscarinic cholinergic receptors. Electro-acupuncture (EA) is used for treating various types of pain via its action through spinal opioidergic and noradrenergic receptors. Here, we investigated whether combined treatment of these two agents could exert a synergistic effect on paclitaxel-induced cold and mechanical allodynia, which were assessed by the acetone drop test and von Frey filament assay, respectively. Significant signs of allodynia were observed after four paclitaxel injections (a cumulative dose of 8 mg/kg, i.p.). GBT (3, 30, and 100 mg/kg, i.p.) or EA (ST36, Zusanli) alone produced dose-dependent anti-allodynic effects. The medium and highest doses of GBT (30 and 100 mg/kg) provided a strong analgesic effect, but they induced motor dysfunction in Rota-rod tests. On the contrary, the lowest dose of GBT (3 mg/kg) did not induce motor weakness, but it provided a brief analgesic effect. The combination of the lowest dose of GBT and EA resulted in a greater and longer effect, without inducing motor dysfunction. This effect on mechanical allodynia was blocked by spinal opioidergic (naloxone, $20{\mu}g$), or noradrenergic (idazoxan, $10{\mu}g$) receptor antagonist, whereas on cold allodynia, only opioidergic receptor antagonist blocked the effect. In conclusion, the combination of the lowest dose of GBT and EA has a robust and enduring analgesic action against paclitaxel-induced neuropathic pain, and it should be considered as an alternative treatment method.

• Journal of Dental Anesthesia and Pain Medicine
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• v.21 no.1
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• pp.1-14
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• 2021

This study aimed to evaluate and compare the pre-emptive analgesic efficacy of injected ketorolac to that of other agents for impacted third molar surgical removal in a healthy population. PubMed, Ovid SP, Cochrane databases were filtered from 1980 to July 2020 for potential papers using relevant MeSH terms and pre-specified inclusion and exclusion criteria independently by reviewers. Studies that compared pre-emptive intramuscular or intravenous administration of ketorolac to other agents were evaluated. The outcomes sought were self-reported postoperative pain (patient-perceived pain), median duration for rescue analgesic medication, total number of analgesics consumed in the recovery period, and global assessment (overall patient satisfaction) after the recovery period. Six studies were included in the final evaluation. The outcome of pain perception and the number of analgesics taken were significantly lower in the ketorolac group (intramuscular or intravenous) in most of the studies (n=5) than in the group of other drugs. The mean time for rescue analgesia intake was higher for the ketorolac group, and global assessment scores were also better in the ketorolac group. Although the included studies show significantly better outcomes such as postoperative pain, median time taken for rescue medication, total number of analgesics taken, and overall patient satisfaction with injected ketorolac group in comparison to injected diclofenac, dexamethasone, and tramadol, definitive conclusions cannot be made regarding the superiority of injected Ketorolac as a pre-emptive agent. A greater number of randomized control trials with a proper protocol are needed to make definitive conclusions.

• Korean Journal of Veterinary Research
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• v.47 no.1
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• pp.103-115
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• 2007

The aim of this study was to compare the reaction of the cardiovascular system, and the anesthetic effect among 3 experimental groups, epidural administration of medetomidine as a single agent, the combination of buprenorphine and medetomidine, and the combination of fentanyl and medetomidine. Twenty one dogs were anesthetized with isoflurane and allowed to breathe spontaneously. Epidural, arterial, and venous catheters were inserted. The tip of epidural catheter was positioned at the level of the space between the sixth and seventh lumbar vertebra. After a stable plane of anesthesia was achieved, these dogs were each administered one of the following treatments epidurally : medetomidine $10{\mu}g/kg$ (Group M), a combination of medetomidine $5{\mu}g/kg$ and buprenorphine $10{\mu}g/kg$ (Group M/B), and a combination of medetomidine $5{\mu}g/kg$ and fentanyl $10{\mu}g/kg$ (Group M/F). Heart rate (HR), Respiratory rate (RR), End-tidal carbon dioxide (EtCO2), and arterial blood pressure were measured before drug administration (base line) and 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, and 60 min postinjection. Blood gas analysis was performed before injection and 5, 15, 25, 35, 45, 60 min postinjection. Isoflurane was discontinued 80 min postinjection and pain/motor function were evaluated up to 260 min postinjection every 15 min. At the early stage of drug introduction (until 5 min), the HR was decreased significantly in all 3 groups compared with base line. In Group M, HR was significantly decreased compared with the other 2 groups. With time (starting 20 min after drug introduction), the HR was decreased significantly in Group M/B in respect to base line. However, no significant difference was seen number-wise in all 3 groups. During 60 min after drug introduction, the systolic, diastolic and mean arterial pressures were highest in Group M and lowest in Group M/F. Among 3 groups, drug action and motor loss duration were longest in Group M/F. Analgesic effect observed in the M/F group was the most prominent and long-lasting, compared to those seen in the other 2 groups. Given the fact that the recovery of motor function takes place in a short period of time after analgesic effects disappeared, additional use of M/F depending on the patient's condition would be a good way to achieve effective pain management. However, proper care should be taken to ensure the function of cardiovascular system in the patient because the administration of M/F under isoflurane anesthesia results in a significant decline in arterial blood pressure ($65{\pm}10mmHg$).

• 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 Pharmacology
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• v.16 no.2 s.27
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• pp.25-29
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• 1980

Etomidoline ($Nonspa^{\circledR}$), which is chemically related to tertiary amine, is new synthetic antispasmodic agent with analgesic action. Antispasmodic effect of this agent is stronger than hyoscine butylbromide ($Buscopan^{\circledR}$), quaternary amine, and the absorption from intestine is also much higher. This study was undertaken to determine the effect of etomidoline on duodenal motility and other smooth muscles of rabbit. Strips of various isolated smooth muscle, 2 cm long from adult rabbits weighting about 2 kg, were suspended in a muscle chamber containing Tyrode's solution, which was bubbled with oxygen gas, and the temperature of the solution was kept constant at $38^{\circ}C$. After being washed with fresh solution several times the strips of smooth muscle attained constant motility and tonus. Etomidoline and other drugs were added in various concentrations to the chamber. Contractility of the strips was measured by using polygraph (Grass, model 7). The results are as follows: 1) In isolated rabbit atrium etomidoline produces a slight depression of contractility and the rate is also decreased. 2) On the other hand, etomidoline relaxed isolated strips of stomach, duodenal, and detrusor of rabbit. This relaxing effect of etomidoline on isolated duodenal strip of rabbit was not blocked by ${\alpha}$-adrenergic blocking agent, phenoxybenzamine, but by ${\beta}$-adrenergic blocking agent, propranolol. 3) Etomidoline did not exert any effect on isolated aorta, gall bladder, and trigone of rabbit. From the above results, it may be concluded that the relaxing effect of etomidoline on duodenal strip is related ${\beta}$-adrenergic receptor.

• BMB Reports
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• v.30 no.1
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• pp.37-40
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• 1997

Earthworm extracts are known for anti-inflammatory, analgesic. antipyretic, and anticancer effects but can also influence blood circulation. It was previously shown that an earthworm, Lumbricus rubelius. contained a water-extractable anticoagulant which was a heat- and acid-stable molecule with hydrophilic property. In order to uncover the biochemical nature of this molecule, the anticoagulant was processed with various hydrolases such as trypsin, DNase, RNase. and lysozome. When the digested samples were analyzed with an in vitro coagulation test measuring activated partial thromboplastin time (APTT) and agarose gel electrophoresis, the anticoagulant proved to be a relatively homogeneous DNA fragment with relative molecular size around 72 base pairs. Interestingly, the activity was further stimulated with a trypsin digestion. RNA. on the other hand, did not prolong the APTT. It was also demonstrated that the DNA accelerated the antithrombin III (AT-III) inhibition of thrombin from $IC_{50}$ of 0.34 to 0.16 unit determined with S-2238 as a substrate, whereas heparin, a popular anticoagulant. shifted the value to 0.05. Therefore, it is suggested that the DNA could be considered as an alternative antithrombotic agent to heparin, which would exhibits bleeding side effects.

• Journal of the Korean Chemical Society
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• v.58 no.1
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• pp.92-99
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• 2014

The pH sensitive hydrogels composed of N-isopropylacrylamide (NIPA) and acryloyl phenylalanine (APA) were prepared by redox polymerization using N,N'-methylenebisacrylamide (MBA) as a crosslinker. Anti-inflammatory and analgesic agent, Keterolac Tromethamine (KT), was loaded successfully into poly(NIPA-co-APA) copolymeric hydrogels by swelling equilibrium method. To understand the nature of drug in the polymeric matrix, the newly synthesized drug loaded poly(NIPA-co-APA) copolymeric hydrogels were characterized by using differential scanning calorimetry (DSC) and X-ray diffraction (XRD) techniques. The scanning electron microscopy (SEM) technique result indicates the spherical smooth surface of the hydrogels. The drug (KT) releasing nature of the poly(NIPA-co-APA) hydrogels was studied in pH 1.2 and 7.4. Effects of drug loading, crosslinking agent, pH and the ionic strength of the external medium on swelling of hydrogels were also investigated.

• YAKHAK HOEJI
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• v.50 no.1
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• pp.47-51
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• 2006

The roots of Dipsacus asper are used in traditional Chinese medicine as an analgesic, enhancement of liver activity, an anti-inflammatory agent and the treatment of fractures. In order to investigate the antioxidative activity, Dipsaci Radix was extracted with MeOH and fractionated with $CHCl_3$, EtOAc, BuOH and water. MeOH ex. and its solvent fractions were determined on the free radical scavenging activity by DPPH method and antioxidative activity on low density lipoprotein oxidation. The EtOAc and BuOH fractions showed antioxidative activities and from their fractions, two compounds were isolated and identified as hederagenin 3-O-${alpha}$-L-arabino pyranoside (compound 1) and O-${\alpha}$-L-arabinopyranosyl hed-eragenin 28-O-${\beta}$-D-glucopyranosyl ($1{\to}6$)-${\beta}$-D-glucopyranosyl ester (compound 2). Saponin glycoside, compound I showed anti-oxidative activity.

• Biomolecules & Therapeutics
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• v.12 no.4
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• pp.198-201
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• 2004

This review focuses on finding neurochemical changes in physical dependence on butorphanol, a relatively potent mixed agonist-antagonist opioid analgesic agent that is five times more potent than morphine in antinociceptive effects. The chronic administration of butorphanol induces physical dependence. Withdrawal from such dependence can be reliably precipitated by administration of a narcotic antagonist, e.g., naloxone. Evidence for critical involvement of excitatory aminoacid (glutamate), opioid receptors, and phosphorylation of proteins in these phenomena is summarized.

• Journal of The Korean Dental Society of Anesthesiology
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• v.12 no.3
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• pp.173-176
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• 2012

Certain oral procedures require a sedated patient who is responsive to allow for the mouth opening and position change. Dexmedetomidine is a relatively selective alpha2-adrenoceptor agonist with sedative, analgesic, amnestic, and anesthetic-sparing effects. Large dose dexmedetomidine is suitable as a single agent for sedation and anxiolysis for plate removal in a patient with bilateral sagittal split osteotomy and Lefort 1 osteotomy with genioplasty.