• Korean Journal of Biological Psychiatry
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• v.19 no.4
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• pp.164-171
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• 2012

The placebo effect, a response observed during the placebo arm of a clinical trial, is produced by the psychobiological action of the placebo as well as by other potential contributors to symptom amelioration such as spontaneous improvement, regression to the mean, biases, concurrent treatments, and study design. From a psychological viewpoint, there are many mechanisms that contribute to placebo effects, including expectations, conditioning, learning, and anxiety reduction. Placebo responses are also mediated by opioid and non-opioid mechanisms including dopamine, serotonin, cholecystokinin, and immune mediators. During recent years, a trend towards increased placebo effects in clinical trials of neuropsychiatric drugs has been noted. Indeed, the placebo effects observed in clinical trials constitute an increasing problem and interfere with signal-detection analyses of potential treatments. Several potential factors including protocol/study design and conduct related factors may account for the placebo effect observed in clinical trials. This paper reviews key issues related to this problem and aims to identify potential solutions.

• The Journal of Korean Medicine
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• v.24 no.4
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• pp.34-42
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• 2003

This study was designed to investigate the modulation of the Corydalis tuber on glycine-activated ion current in rat periaqueductal gray (PAG) neurons. Aqueous extract from Corydalis tuber has been widely used for pain control such as dysmenorrhea, irregular menstruation or amenorrhea with abdominal cramping, neuralgia, headache and gastrointestinal spasm. The PAG region of the brain is known to be involved heavily with nociception. Modulation of the Corydalis tuber on glycine-induced ion current in rat periaqueductal gray (PAG) neurons was studied by a nystatin-perforated patch-clamp technique. High concentrations of Corydalis tuber elicited ion current, which was suppressed by strychnine application. Low concentrations of Corydalis tuber reduced glycine-induced ion currents in the PAG neurons. Inhibitory action of Corydalis tuber on glycine-activated ion current was reduced by treatment with naltrexone, a non- selective opioid antagonist. Application of N-methylmalemide (NEM), a sulfhydryl alkylating agent, also reduced the inhibitory action of Corydalis tuber on glycine-activated ion current in the PAG neurons. These results suggest that the inhibitory effect of Corydalis tuber on glycine-activated ion current in the PAG neurons is one of the analgesic mechanisms of the Corydalis tuber, which may activate descending pain control system in PAG neurons.

• Tuberculosis and Respiratory Diseases
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• v.68 no.5
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• pp.286-289
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• 2010

A 55-year old woman with advanced stage non-small cell lung cancer was admitted to hospital for the management of severe chest pain, which measured 7 out of 10 on a numerical rating scale (NRS). Despite palliative radiation and the application of multiple epidural blocks, she continued to experience severe cancer pain. We gradually increased the dose of transdermal fentanyl patches from $500{\mu}g/hr$ to $3,650{\mu}g/hr$, for 3 months without any significant side effects. Concomitantly, adjuvant therapy with antidepressants and anticonvulsants were added, decreasing the patient's pain to NRS 3~4 down from 7. After being transferred to a hospice clinic, her chest pain was well-controlled below NRS 4 by means of strong opioid medications, including the highest dose of transdermal fentanyl $4,050{\mu}g/hr$ for more than 16 months.

• Biomolecules & Therapeutics
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• v.26 no.2
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• pp.101-108
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• 2018

G protein-coupled receptors (GPCRs) are the largest superfamily of transmembrane receptors and have vital signaling functions in various organs. Because of their critical roles in physiology and pathology, GPCRs are the most commonly used therapeutic target. It has been suggested that GPCRs undergo massive genetic variations such as genetic polymorphisms and DNA insertions or deletions. Among these genetic variations, non-synonymous natural variations change the amino acid sequence and could thus alter GPCR functions such as expression, localization, signaling, and ligand binding, which may be involved in disease development and altered responses to GPCR-targeting drugs. Despite the clinical importance of GPCRs, studies on the genotype-phenotype relationship of GPCR natural variants have been limited to a few GPCRs such as b-adrenergic receptors and opioid receptors. Comprehensive understanding of non-synonymous natural variations within GPCRs would help to predict the unknown genotype-phenotype relationship and yet-to-be-discovered natural variants. Here, we analyzed the non-synonymous natural variants of all non-olfactory GPCRs available from a public database, UniProt. The results suggest that non-synonymous natural variations occur extensively within the GPCR superfamily especially in the N-terminus and transmembrane domains. Within the transmembrane domains, natural variations observed more frequently in the conserved residues, which leads to disruption of the receptor function. Our analysis also suggests that only few non-synonymous natural variations have been studied in efforts to link the variations with functional consequences.

• Journal of Korean Clinical Nursing Research
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• v.30 no.1
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• pp.45-53
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• 2024

Purpose: This study aimed to investigate the effectiveness of preoperative patient-controlled analgesia(PCA) education program on older patients with spine surgery. Methods: A quasi-experimental research with a non-equivalent control group pretest-posttest design was conducted to investigate the impact of a PCA education program before surgery on postoperative pain, pain knowledge and attitudes, and frequency of additional analgesic use. The sample size for experimental and control group was 55 respectively. Results: The experimental group, which underwent the PCA education program, had lower postoperative pain scores compared to the control group. Furthermore, the experimental group exhibited a higher level of knowledge on PCA (p<.001) and more positive attitudes toward analgesic use (p<.001). While there was a significant difference in the use of opioid analgesics for additional pain relief between two groups (p<.001), there was no significant difference in the use of non-opioid analgesics. Conclusion: The implementation of the PCA education program was found to increase knowledge and positive attitudes on the use of PCA. Moreover, it significantly alleviated pain, particularly during physical activity, within initial 48 hours after spinal surgey in older patients. Therefore, the findings of this study supported that the PCA education program could be used as a preoperative intervention to alleviate postoperative pain for older patients with spinal surgery.

• The Korean Journal of Pain
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• v.37 no.3
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• pp.211-217
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• 2024

Background: Tolerance to the analgesic effects of opioids and non-steroidal anti-inflammatory drugs (NSAIDs) is a major concern for relieving pain. Thus, it is highly valuable to find new pharmacological strategies for prolonged therapeutic procedures. Biguanide-type drugs such as metformin (MET) are effective for neuroprotection and can be beneficial for addressing opioid tolerance in the treatment of chronic pain. It has been proposed that analgesic tolerance to NSAIDs is mediated by the endogenous opioid system. According to the cross-tolerance between NSAIDs, especially sodium salicylate (SS), and opiates, especially morphine, the objective of this study was to investigate whether MET administration can reduce tolerance to the anti-nociceptive effects of SS. Methods: Fifty-six male Wistar rats were used in this research (weight 200-250 g). For induction of tolerance, SS (300 mg/kg) was injected intraperitoneally for 7 days. During the examination period, animals received MET at doses of 50, 75, or 100 mg/kg for 7 days to evaluate the development of tolerance to the analgesic effect of SS. The hot plate test was used to evaluate the drugs' anti-nociceptive properties. Results: Salicylate injection significantly increased hot plate latency as compared to the control group, but the total analgesic effect of co-treatment with SS + Met50 was stronger than the SS group. Furthermore, the effect of this combination undergoes less analgesic tolerance over time. Conclusions: It can be concluded that MET can reduce the analgesic tolerance that is induced by repeated intraperitoneal injections of SS in Wister rats.

• The Korean Journal of Pain
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• v.37 no.3
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• pp.218-232
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• 2024

Background: Cynara scolymus has bioactive constituents and has been used for therapeutic actions. The present study was undertaken to investigate the mechanisms underlying pain-relieving effects of the hydroethanolic extract of C. scolymus (HECS). Methods: The antinociceptive activity of HECS was assessed through formalin and acetic acid-induced writhing tests at doses of 50, 100 and 200 mg/kg intraperitoneally. Additionally, naloxone (non-selective opioid receptors antagonist, 2 mg/kg), atropine (non-selective muscarinic receptors antagonist, 1 mg/kg), chlorpheniramine (histamine H₁-receptor antagonist, 20 mg/kg), cimetidine (histamine H₂-receptor antagonist, 12.5 mg/kg), flumazenil (GABA_A/BDZ receptor antagonist, 5 mg/kg) and cyproheptadine (serotonin receptor antagonist, 4 mg/kg) were used to determine the systems implicated in HECS-induced analgesia. Impact of HECS on locomotor activity was executed by open-field test. Determination of total phenolic content (TPC) and total flavonoid content (TFC) was done. Evaluation of antioxidant activity was conducted employing 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay. Results: HECS (50, 100 and 200 mg/kg) significantly indicated dose dependent antinociceptive activity against pain-related behavior induced by formalin and acetic acid (P < 0.001). Pretreatment with naloxone, atropine and flumazenil significantly reversed HECS-induced analgesia. Antinociceptive effect of HECS remained unaffected by chlorpheniramine, cimetidine and cyproheptadine. Locomotor activity was not affected by HECS. TPC and TFC of HECS were 59.49 ± 5.57 mgGAE/g dry extract and 93.39 ± 17.16 mgRE/g dry extract, respectively. DPPH free radical scavenging activity (IC₅₀) of HECS was 161.32 ± 0.03 ㎍/mL. Conclusions: HECS possesses antinociceptive activity which is mediated via opioidergic, cholinergic and GABAergic pathways.

• Korean Journal of Acupuncture
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• v.34 no.4
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• pp.265-270
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• 2017

Objectives : The present study aimed to examine the analgesic effect of electroacupuncture(EA) applied to the brook point of the Liver meridian in the rat model of inflammatory pain and to investigate involvement of endogenouse opioid in the EA-induced analgesia. Methods : Knee arthritis was induced by injection of $125{\mu}l$ of complete Freund's adjuvant into the knee joint cavity unilaterally. To examine the level of pain, weight bearing forces(WBFs) of affected limb was measured. EA treatment was given at the LR2, LI4 or non-acupoint on the contralateral limb with frequency of 2 Hz and intensity of 2 mA under gaseous anesthesia. Results : After induction of arthritis, rats subsequently showed a reduced stepping force of the affected hindlimb due to a painful knee. EA applied to the LR2 point on the contralateral hind limb produced a significant improvement of stepping force of the hind limb lasting for at least 2 h, and this effect was equivalent to that obtained by 5 mg/kg of oral indomethacin. The effect of EA was specific to the acupoint since it could not be mimicked by EA applied to the LI4 point or the arbitrary non-acupoint. The analgesic effect was blocked by pretreatment with naltrexone(10 mg/kg, i.p.). Conclusions : These results suggest that acupuncture applied to LR2, brook point of Liver meridian suppresses inflammatory pain in a rat model of knee arthritis and this effect seems to be mediated by endogenous opioid systems.

• Journal of the Korean Orthopaedic Association
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• v.55 no.1
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• pp.1-8
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• 2020

The progression of aging and the increase in musculoskeletal diseases have led to an increase in invasive treatment methods, including various surgical methods, but conservative treatment should be attempted before surgical treatment in musculoskeletal diseases. Medication for pain control, such as acetaminophen, non-steroidal anti-inflammatory drugs, steroid, opioids, antidepressants, etc., is one of the most popular methods for pain control. If the pain receptors on peripheral organ are stimulated, pain is transmitted to the brain by the ascending pathway, and the brain then secretes endogenous opioids, such as endorphin, by the descending pathway for pain control. Opioids are substances that act on the opioid receptors, and there are three receptors for opioids. The affinity for each receptor varies according to the tissue and the patient's systemic status. Antidepressants work on the synapses in the central nervous system and its main mechanism is regulation of the ascending pathway. This is mainly effective in chronic pain and neuropathic pain, which is similar in effectiveness to opioids. This review focuses on the effectiveness, method of use, and side effects of opioids and antidepressants.

• The Korean Journal of Pain
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• v.26 no.3
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• pp.255-264
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• 2013

Background: We investigated the effects of pre-emptive administration of ketamine and norBNI on pain behavior and the expression of DREAM, c-Fos, and prodynorphin proteins on the ipsilateral side of the rat spinal cord at 2 and 4 hours after formalin injection. Methods: Eighty-four male Sprague Dawley rats were divided into 4 major groups consisting of control rats (C) (n = 12), rats given only formalin injections (F) (n = 24), and rats treated with pre-emptive administration of either ketamine (K+F) (n = 24) or norBNI (N+F) (n = 24). The non-control groups were further divided into subgroups consisting of rats that were sacrificed at 2 and 4 hours (n = 12 for each group) after formalin injection. Pain behavior was recorded for 1 hour. After 2 and 4 hours, the rats were sacrificed and the spinal cords (L4-L5 sections) were removed for immunohistochemistry and Western blot analysis. Results: The pain behavior response was reduced in the K+F group compared to the other groups during the second phase of the formalin pain response. We detected an increase in the nuclear DREAM protein level in the K+F group at 2 and 4 hours and a transient decrease in the N+F group at 2 hours; however, it increased at 4 hours after injection. Fos-like immunoreactivity (FLI) and Prodynorphin-like immunoreactivity (PLI) neurons decreased in the K+F group but increased in the N+F group at 2 hours after injection. While FLI decreased, PLI increased in all groups at 4 hours after injection. Conclusions: We suggest that NMDA and kappa opioid receptors can modulate DREAM protein expression, which can affect pain behavior and protein transcriptional processes at 2 hours and bring about either harmful or protective effects at 4 hours after formalin injection.