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1.  Evaluation of the neurological safety of epidurally-administered pregabalin in rats 
Background
The primary site of action of pregabalin, i.e. the α-2-δ subunit of the voltage-dependent calcium channel, is located at the dorsal root ganglion and dorsal horn of the spinal cord. Therefore, the epidural administration of pregabalin could have advantages over oral administration. However, the possibility of its neurotoxicity should be excluded before any attempt at epidural administration. We evaluated the neuronal safety of epidurally-administered pregabalin by observing the sensory/motor changes and examining the histopathology of spinal cord in rats.
Methods
Sixty rats of 180-230 g were divided into three groups; 3 mg of pregabalin dissolved in 0.3 ml saline (group P, n = 20), 0.3 ml 40% alcohol (group A, n = 20), or 0.3 ml normal saline (group N, n = 20) was administered epidurally to the rats in each group. Pinch-toe test, motor function evaluation, and histopathologic examination of vacuolation, chromatolysis, meningeal inflammation, and neuritis were performed at the 1st, 3rd, 7th, and 21st day after each epidural administration.
Results
All rats enrolled in group P, like those in group N, showed neither sensory/motor dysfunction nor any histopathological abnormality over the 3-week observation period. In contrast, in group A, 80% of the rats showed abnormal response to the pinch-toe test and all rats showed decreased motor function during the entire evaluation period. In addition, all histopathologic findings of neurotoxicity were observed exclusively in group A.
Conclusions
The epidurally administered pregabalin (about 15 mg/kg) did not cause any neurotoxic evidence, in terms of both sensory/motor function evaluation and histopathological examination in rats.
doi:10.4097/kjae.2012.62.1.57
PMCID: PMC3272531  PMID: 22323956
Epidural injection; Neurotoxicity; Pregabalin
2.  Psychometric Characteristics of the Korean Version of the Roland-Morris Disability Questionnaire 
Journal of Korean Medical Science  2011;26(10):1364-1370.
The aims of this study were; 1) to develop the final version of the Korean Roland-Morris Disability Questionnaire (RDQ), and 2) to compare the responsiveness between the RDQ and the Oswestry Disability Index (ODI) scores in patients having low back pain. The psychometric properties of the final Korean RDQ were evaluated in 221 patients. Among them, 30 patients were reliability tested. Validity was evaluated using an 11-point numerical rating scale (NRS) and the Korean ODI. The receiver operating characteristic (ROC) curve analysis of the RDQ and the ODI was compared in 54 patients with lumbar zygapophyseal (facet) joint pain. There was a moderate relationship between the RDQ and NRS (r = 0.59, P < 0.01) and a strongly positive correlation between the RDQ and the ODI (r = 0.76, P < 0.001). The Korean RDQ with the higher area under the ROC curve showed a better overall responsive performance than did the ODI in patients with lumbar facet joint pain after medial branch radiofrequency neurotomy (P < 0.01). The results of the study present the final version of the Korean RDQ is valid for assessing functional status in a Korean population with chronic low back pain.
doi:10.3346/jkms.2011.26.10.1364
PMCID: PMC3192350  PMID: 22022191
Low Back Pain; Oswestry Disability Index; Psychometric Properties; Roland-Morris Disability Questionnaire
3.  Occipital nerve stimulation in a patient with an intractable chronic headache -A case report- 
Korean Journal of Anesthesiology  2011;60(4):298-301.
Occipital nerve stimulation (ONS) is a form of peripheral nerve stimulation used to treat refractory headaches. The trial of ONS was carried with the midline incision C1-2 level, inserted electrical lead subcutaneously to oblique and cephalad direction followed by trajectory of blunt dissection. We used 8 pole electrical lead to cover lesser occipital nerve, greater occipital nerve, third occipital nerve and great auricular nerve. We anchored the lead at the midline insertion site after confirming the stimulation of the patient. And then we looped and tightened the lead loosely, connected the lead and the extension under right supraspinatus muscle region. After 1 week trial period, we performed the permanent implantation of occipital nerve stimulator. We inserted internal pulse generator under a pocket located at right infraclavicular region. The VAS score dropped from 8/10 to 1-2/10. No serious complications were detected during 1 month follow-up.
doi:10.4097/kjae.2011.60.4.298
PMCID: PMC3092968  PMID: 21602983
Headache; Occipital nerve stimulation; Occipital neuralgia; Peripheral nerve stimulation
4.  Cervicogenic headache arising from hidden metastasis to cervical lymph node adjacent to the superficial cervical plexus -A case report- 
Korean Journal of Anesthesiology  2011;60(2):134-137.
The differential diagnosis of headache is often difficult because the symptom of headache is overlapping. Superficial cervical plexus block is useful in diagnosis and treatment of headache. Headache arising from the neck and radiating to the frontotemporal regions and possibly to the supraorbital region has been defined as cervicogenic headache. A positive response to anesthetic blocks is one of the diagnostic criteria of cervicogenic headache. We experienced a case of headache arising from direct lymph node metastasis of hepatocellular carcinoma adjacent to the superficial cervical plexus during treatment of cervicogenic headache under ultrasonographic guidance. Especially in patients with medical history of cancer, practitioners should consider the possibility of metastasis to cervical lymph nodes and using ultrasonography to evaluate the cervical area prior to the practice.
doi:10.4097/kjae.2011.60.2.134
PMCID: PMC3049882  PMID: 21390170
Cervicogenic headache; Diagnostic block; Metastasis; Superficial cervical plexus; Ultrasonography
5.  Neuroimaging Studies of Chronic Pain 
The Korean Journal of Pain  2010;23(3):159-165.
The evolution of brain imaging techniques over the last decade has been remarkable. Along with such technical developments, research into chronic pain has made many advances. Given that brain imaging is a non-invasive technique with great spatial resolution, it has played an important role in finding the areas of the brain related to pain perception as well as those related to many chronic pain disorders. Therefore, in the near future, brain imaging techniques are expected to be the key to the discovery of many unknown etiologies of chronic pain disorders and to the subjective diagnoses of such disorders.
doi:10.3344/kjp.2010.23.3.159
PMCID: PMC2935976  PMID: 20830260
brain imaging; chronic pain
6.  Development of Korean Academy of Medical Sciences Guideline-Rating the Impairment in Pain 
Journal of Korean Medical Science  2009;24(Suppl 2):S330-S337.
Pain-related impairment assessment by the fifth edition of the American Medical Association Guides had many ambiguous points, and therefore, it was not applicable directly in Korea. Several disputable pain disorders were excluded from the list of impairment evaluation, and complex regional pain syndrome was chosen as the first object of impairment evaluation. Scales such as Korean version of modified Barthel index for assessing the activity of daily livings and Beck Depression Inventory for assessing depression were added, and pain severity, pain treatment, pain behavior, etc. were scored. In order to objectify as much as possible and to remove the room for misuse, we develop a new rating system based on the concept of total score.
doi:10.3346/jkms.2009.24.S2.S330
PMCID: PMC2690066  PMID: 19503691
Pain; Disability Evaluation; Complex Regional Pain Syndrome
7.  Epidemiology of Complex Regional Pain Syndrome: A Retrospective Chart Review of 150 Korean Patients 
Journal of Korean Medical Science  2008;23(5):772-775.
Complex regional pain syndrome (CRPS) is a chronically painful and disabling disorder. However, no data are available even on the epidemiology of CRPS in Korea. This study was undertaken to retrospectively assess the epidemiologic characteristics of CRPS in 150 consecutive patients at a tertiary chronic pain center from March 2002 to February 2006. Information was obtained regarding patients' demographics, nature of injury, and treatment modalities. Seventy-one percent of patients had CRPS type I. The mean 11-point verbal numerical rating scale score at initial examinations and at the time of study were 8.0 and 5.7, respectively. Thirty-two percent of patients showed no change or increase in pain intensity during follow-up at our pain center. The mean duration of CRPS symptoms prior to our pain center evaluation and prior to the time of study were 27 months and 50 months, respectively. These patients had seen on average 5 different physicians before being referred to our center. This study shows that the majority of CRPS patients were referred to our center after more than 2 yr of symptoms. The clinical implication of such delayed transfer and strategies to avoid this problem are discussed.
doi:10.3346/jkms.2008.23.5.772
PMCID: PMC2580014  PMID: 18955780
Complex Regional Pain Syndromes; Epidemiology; Treatment
9.  Structurally related nucleotides as selective agonists and antagonists at P2Y1 receptors 
The P2Y1 receptor responds to adenine nucleotides and is present in platelets, heart, smooth muscles prostate, ovary, and brain. A selective antagonist may be useful as an antithrombotic agent. We have analyzed the binding site of this G protein-coupled receptor using ligand design, site-directed mutagenesis, and homology modeling based on rhodopsin. We have designed and synthesized a series of deoxyadenosine 3′,5′-bisphosphate derivatives that act as antagonists, or, in some cases with small structural changes, as agonists or partial agonists. The 2-position accommodates Cl or thioethers, whereas the N6-position is limited to Me or Et. 2′-Substitution with OH or OMe increases agonist efficacy over 2′-H. Using molecular modeling of the binding site, the oxygen atoms of the ribose moiety were predicted to be non-essential, i.e. no specific H-bonds with the receptor protein appear in the model. We have, therefore, substituted this moiety with carbocylics, smaller and larger rings, conformationally constrained rings, and acyclics, with retention of affinity for the receptor. With simplified pharmacophores we are exploring the steric and electronic requirements of the receptor binding site, and the structural basis of receptor activation.
PMCID: PMC4313380  PMID: 11347970
G protein-coupled receptors; Nucleotides; P2Y1; Molecular modeling
10.  Adenosine A3 Receptor Agonists Protect HL-60 and U-937 Cells from Apoptosis Induced by A3 Antagonists 
The effects of novel, selective adenosine (ADO) A3 receptor antagonists of diverse structure on cells of the human HL-60 leukemia and U-937 lymphoma cell lines were examined. Both 3-ethyl 5-benzyl 2-methyl-6-phenyl-4-phenylethynyl-1,4-(±)-dihydropyridine3,5-dicarboxylate (MRS 1191, 0.5µM) and 6-carboxymethyl-5,9-dihydro-9-methyl-2-phenyl-[1,2,4]-triazolo[5,1-a][2,7]naphthyridine (L-249313, 0.5 µM) induced apoptotic cell death and expression of bak protein. Low concentrations of the A3 receptor agonist 2-chloro-N6-(3-iodobenzyl)adenosine-5′-N-methyluxonamide (Cl-IB-MECA, 10 nM or 1 µM) protected against antagonist-induced cell death. At concentrations ≥ 10 µM, the agonist alone produced apoptosis and bak expression in various cell lines. It is suggested that there exists a tonic low level of A3 receptor activation, possibly induced by release of endogenous adenosine, that results in cell protection.
doi:10.1006/bbrc.1997.6290
PMCID: PMC4309999  PMID: 9125172
11.  The Value of SPECT/CT in Localizing Pain Site and Prediction of Treatment Response in Patients with Chronic Low Back Pain 
Journal of Korean Medical Science  2014;29(12):1711-1716.
In many circumstances, causing sites of low back pain (LBP) cannot be determined only by anatomical imaging. Combined functional and morphological imaging such as bone scan with single-photon emission computed tomography/computed tomography (SPECT/CT) may be helpful in identifying active lesions. The purpose of this study was to evaluate the usefulness of bone SPECT/CT in localizing the pain site and the treatment of chronic LBP. One hundred seventy-five patients suffering from chronic LBP who underwent SPECT/CT were included, retrospectively. All of the patients received multiple general treatments according to the symptoms, and some of them underwent additional target-specific treatment based on SPECT/CT. Numerical rating scale (NRS) pain score was used to assess the pain intensity. Of 175 patients, 127 showed good response to the given therapies, while the rest did not. Overall, 79.4% of patients with definite active lesions showed good response. Patients with mild active or no lesions on SPECT/CT had relatively lower response rate of 63.0%. Good response was observed by the treatment with the guidance of active lesions identified on SPECT/CT. SPECT/CT could be useful in identifying active lesions in patients with chronic LBP and guiding the clinicians to use adequate treatment.
Graphical Abstract
doi:10.3346/jkms.2014.29.12.1711
PMCID: PMC4248596  PMID: 25469075
Low Back Pain; Tomography, Emission-Computed, Single-Photon; Tomography, X-Ray Computed; Pain Management; Technetium-99m (Tc-99m), Methylene Diphosphonate (MDP)
12.  The relationship between perioperative nausea and vomiting and serum serotonin concentrations in patients undergoing cesarean section under epidural anesthesia 
Korean Journal of Anesthesiology  2014;67(6):384-390.
Background
Serotonin-also known as 5-hydroxytryptamine or 5-HT-can induce nausea and vomiting (NV) by peripheral mechanisms via the activation of 5-HT3 receptors. In this study, we observed perioperative NV, including intraoperative NV, and changes in serum 5-HT concentrations. We evaluated the relationship between perioperative NV and serum 5-HT levels in patients undergoing cesarean section under epidural anesthesia, and carried out a pilot study to determine if further studies on a larger scale were justified.
Methods
Twenty-eight patients who were scheduled for cesarean section under epidural anesthesia were included in the study. Patients were assigned to 2 groups according to the occurrence of NV after induction, i.e., an NV-positive or an NV-negative group. Serum 5-HT concentrations were measured before induction, at the time that NV occurred (in the case of the NV-positive group) or 5 min after the umbilical cord clamping (in the case of the NV-negative group) during surgery, and at 2 h postoperatively.
Results
NV occurred in 10 of the 28 patients. No significant differences in serum 5-HT concentrations were found within or between the two groups.
Conclusions
This study suggests that there is no correlation between serum 5-HT concentration and the occurrence of perioperative NV in patients undergoing cesarean section under epidural anesthesia, and the findings do not seem to support further investigations regarding a possible relationship between serum 5-HT concentration and perioperative NV.
doi:10.4097/kjae.2014.67.6.384
PMCID: PMC4280475  PMID: 25558338
Cesarean section; Epidural anesthesia; Perioperative nausea and vomiting; Serum serotonin
13.  Proteomic Identification of Altered Cerebral Proteins in the Complex Regional Pain Syndrome Animal Model 
BioMed Research International  2014;2014:498410.
Background. Complex regional pain syndrome (CRPS) is a rare but debilitating pain disorder. Although the exact pathophysiology of CRPS is not fully understood, central and peripheral mechanisms might be involved in the development of this disorder. To reveal the central mechanism of CRPS, we conducted a proteomic analysis of rat cerebrum using the chronic postischemia pain (CPIP) model, a novel experimental model of CRPS. Materials and Methods. After generating the CPIP animal model, we performed a proteomic analysis of the rat cerebrum using a multidimensional protein identification technology, and screened the proteins differentially expressed between the CPIP and control groups. Results. A total of 155 proteins were differentially expressed between the CPIP and control groups: 125 increased and 30 decreased; expressions of proteins related to cell signaling, synaptic plasticity, regulation of cell proliferation, and cytoskeletal formation were increased in the CPIP group. However, proenkephalin A, cereblon, and neuroserpin were decreased in CPIP group. Conclusion. Altered expression of cerebral proteins in the CPIP model indicates cerebral involvement in the pathogenesis of CRPS. Further study is required to elucidate the roles of these proteins in the development and maintenance of CRPS.
doi:10.1155/2014/498410
PMCID: PMC4182003  PMID: 25313364
14.  Analysis of Correlation between 24-Hour Urinary Sodium and the Degree of Blood Pressure Control in Patients with Chronic Kidney Disease and Non-Chronic Kidney Disease 
Journal of Korean Medical Science  2014;29(Suppl 2):S117-S122.
We investigated the association between 24-hr urinary sodium (24UNA) and adequacy of blood pressure (BP) control in patients with chronic kidney disease (CKD) and nonCKD. All data were collected retrospectively by accessing the electrical medical records in patients with 24-hr urine collection and serum creatinine. Enrolled 400 subjects were subgrouped by the amount of 24UNA, or CKD stage. The appropriate BP was defined as BP < 130/80 mmHg for subjects with proteinuria, and BP < 140/90 mmHg for subjects without proteinuria. The mean level of 24UNA was 166±76 mEq/day. The 24UNA group was an independently related factor to diastolic BP as a continuous variable. The rate of appropriate BP control in patients with proteinuria was highest in 24UNA <100 mEq/L (P=0.012). The odds to fail achievement of BP target in subjects with 24UNA≥90 mEq/day was 2.441 (1.249-4.772, P=0.009) higher than that of 24UNA <90 mEq/day among participants with proteinuria. There was difference in the amount of 24UNA between CKD and non-CKD except each stage of CKD group. In conclusion, salt intake estimated by 24-hr urine sodium excretion is a risk factor to achieve appropriate BP control.
Graphical Abstract
doi:10.3346/jkms.2014.29.S2.S117
PMCID: PMC4194281  PMID: 25317015
Salt; Hypertension; Blood pressure; Renal insufficiency
15.  Estimated Amount of 24-Hour Urine Sodium Excretion Is Positively Correlated with Stomach and Breast Cancer Prevalence in Korea 
Journal of Korean Medical Science  2014;29(Suppl 2):S131-S138.
Stomach cancer is one of the most common cancers in Korea. The aim of this study was to identify the association between the prevalence of cancer, particularly stomach cancer, and the amount of 24-hr urine sodium excretion estimated from spot urine specimens. The study included 19,083 subjects who took part in the Korean National Health and Nutritional Examination Survey between 2009 and 2011. The total amount of urine sodium excreted in a 24-hr period was estimated by using two equations based on the values for spot urine sodium and creatinine. In subjects who had an estimated 24-hr urine sodium excretion of more than two standard deviations above the mean (group 2), the prevalence of stomach cancer was higher than in subjects with lower 24-hr sodium excretion (group 1). By using the Tanaka equation to estimate it, the prevalence of stomach cancer was 0.6% (114/18,331) in group 1, whereas it was 1.6% (9/568) in group 2 (P=0.006). By using the Korean equation, the prevalence was 0.6% (115/18,392) in group 1, and 1.6% in group 2 (8/507) (P=0.010). By using the Tanaka equation, breast cancer in women is more prevalent in group 2 (1.9%, 6/324) than group 1 (0.8%, 78/9,985, P=0.039). Higher salt intake, as defined by the estimated amount of 24-hr urine sodium excretion, is positively correlated with a higher prevalence of stomach or breast cancer in the Korean population.
Graphical Abstract
doi:10.3346/jkms.2014.29.S2.S131
PMCID: PMC4194283  PMID: 25317017
24-Hour Urine Sodium; Spot Urine Sodium; Cancer
16.  Estimation of Daily Salt Intake through a 24-Hour Urine Collection in Pohang, Korea 
Journal of Korean Medical Science  2014;29(Suppl 2):S87-S90.
There is an established relationship between a high salt diet and public health problems, especially hypertension and cardiovascular disease. We estimated daily salt intake in a group of adults and assessed its association with related variables in Pohang, Korea. We conducted a cross-sectional survey in 2013 with 242 adults. Urine was collected for 24 hr to estimate daily salt intake, and questionnaires about salt preference were administered. The mean daily salt intake was 9.9±4.6 g. There was no difference in salt intake between high systolic blood pressure (SBP) participants and normal SBP participants (10.5±4.7 g/d vs. 9.6±4.3 g/d, P=0.339), but high diastolic blood pressure (DBP) participants reported more salt intake than normal DBP participants (10.4±4.9 g/d vs. 9.7±4.1 g/d, P=0.049). Salt intake and body mass index demonstrated a positive correlation (P=0.001). A preference for Korean soup or stew was associated with high salt intake (P=0.038). Dietary salt intake in Korean adults is still higher than the recommendation from the World Health Organization. More efforts should be made to reduce the salt consumption of Korean adults.
doi:10.3346/jkms.2014.29.S2.S87
PMCID: PMC4194289  PMID: 25317022
Salt Intake; 24-hr Urine Collection; Hypertension; Public Health
17.  Not Salt Taste Perception but Self-Reported Salt Eating Habit Predicts Actual Salt Intake 
Journal of Korean Medical Science  2014;29(Suppl 2):S91-S96.
Excessive dietary salt intake is related to cardiovascular morbidity and mortality. Although dietary salt restriction is essential, it is difficult to achieve because of salt palatability. However, the association between salt perception or salt eating habit and actual salt intake remains uncertain. In this study, we recruited 74 healthy young individuals. We investigated their salt-eating habits by questionnaire and salt taste threshold through a rating scale that used serial dilution of a sodium chloride solution. Predicted 24-hr urinary salt excretions using Kawasaki's and Tanaka's equations estimated dietary salt intake. Participants' mean age was 35 yr, and 59.5% were male. Salt sense threshold did not show any relationship with actual salt intake and a salt-eating habit. However, those eating "salty" foods showed higher blood pressure (P for trend=0.048) and higher body mass index (BMI; P for trend=0.043). Moreover, a salty eating habit was a significant predictor for actual salt intake (regression coefficient [β] for Kawasaki's equation 1.35, 95% confidence interval [CI] 10-2.69, P=0.048; β for Tanaka's equation 0.66, 95% CI 0.01-1.31, P=0.047). In conclusion, a self-reported salt-eating habit, not salt taste threshold predicts actual salt intake.
Graphical Abstract
doi:10.3346/jkms.2014.29.S2.S91
PMCID: PMC4194290  PMID: 25317023
Salt-Eating Habit; Salt Taste Threshold; Salt Intake
18.  Estimating 24-Hour Urine Sodium Level with Spot Urine Sodium and Creatinine 
Journal of Korean Medical Science  2014;29(Suppl 2):S97-S102.
The 24-hr urine sodium excretion level was estimated based on the spot urine sodium, and the efficacy of the formula was validated to determine the status of low salt intake <100 mEq Na/day. The 24-hr urine samples were collected from 400 patients. The 24-hr urine creatinine level was estimated with the use of three formulas: a newly derived Korean equation (E24UCR_K), and Tanaka (E24UCR_T) and Cockcroft-Gault (E24UCR_CG) equations. The correlation coefficients between the estimated and measured 24-hr urine creatinine for these three equations were 0.863, 0.846, and 0.896, respectively (All P<0.001). After estimating the 24-hr urine sodium levels, the correlation coefficients between the estimated and measured 24-hr urine sodium levels were 0.466, 0.490, and 0.516, respectively (All P<0.001). The sensitivity of three formulas to estimate the measured 24-hr urine sodium≥100 mEq/day using the estimated amount≥100 mEq/day was 84.3%, 87.6%, and 84.8%, respectively. In conclusion, the three equations used to estimate the 24-hr urine sodium content were useful to determine the status of low salt intake.
Graphical Abstract
doi:10.3346/jkms.2014.29.S2.S97
PMCID: PMC4194291  PMID: 25317024
24-hr Urine Sodium; Spot Urine Sodium; Spot Urine Creatinine
19.  Therapeutic Effect of Epidurally Administered Lipo-Prostaglandin E1 Agonist in a Rat Spinal Stenosis Model 
The Korean Journal of Pain  2014;27(3):219-228.
Background
A lipo-prostaglandin E1 agonist is effective for the treatment of neurological symptoms of spinal stenosis when administered by an oral or intravenous route. we would like to reveal the therapeutic effect of an epidural injection of lipo-prostaglandin E1 on hyperalgesia in foraminal stenosis.
Methods
A total of 40 male Sprague-Dawley rats were included. A small stainless steel rod was inserted into the L5/L6 intervertebral foramen to produce intervertebral foraminal stenosis and chronic compression of the dorsal root ganglia (DRG). The rats were divided into three groups: epidural PGE1 (EP) (n = 15), saline (n = 15), and control (n = 10). In the EP group, 0.15 µg.kg-1 of a lipo-PGE1 agonist was injected daily via an epidural catheter for 10 days from postoperative day 3. In the saline group, saline was injected. Behavioral tests for mechanical hyperalgesia were performed for 3 weeks. Then, the target DRG was analyzed for the degree of chromatolysis, chronic inflammation, and fibrosis in light microscopic images.
Results
From the fifth day after lipo-PGE1 agonist injection, the EP group showed significant recovery from mechanical hyperalgesia, which was maintained for 3 weeks (P < 0.05). Microscopic analysis showed much less chromatolysis in the EP group than in the saline or control groups.
Conclusions
An epidurally administered lipo-PGE1 agonist relieved neuropathic pain, such as mechanical hyperalgesia, in a rat foraminal stenosis model, with decreasing chromatolysis in target DRG. We suggest that epidurally administered lipo-PGE1 may be a useful therapeutic candidate for patients with spinal stenosis.
doi:10.3344/kjp.2014.27.3.219
PMCID: PMC4099234  PMID: 25031807
epidural administration; hyperalgesia; spinal stenosis
20.  Potential Role of Bacterial Infection in Autoimmune Diseases: A New Aspect of Molecular Mimicry 
Immune Network  2014;14(1):7-13.
Molecular mimicry is an attractive mechanism for triggering autoimmunity. In this review, we explore the potential role of evolutionary conserved bacterial proteins in the production of autoantibodies with focus on granulomatosis with polyangiitis (GPA) and rheumatoid arthritis (RA). Seven autoantigens characterized in GPA and RA were BLASTed against a bacterial protein database. Of the seven autoantigens, proteinase 3, type II collagen, binding immunoglobulin protein, glucose-6-phosphate isomerase, α-enolase, and heterogeneous nuclear ribonuclear protein have well-conserved bacterial orthologs. Importantly, those bacterial orthologs are also found in human-associated bacteria. The wide distribution of the highly conserved stress proteins or enzymes among the members of the normal flora and common infectious microorganisms raises a new question on how cross-reactive autoantibodies are not produced during the immune response to these bacteria in most healthy people. Understanding the mechanisms that deselect auto-reactive B cell clones during the germinal center reaction to homologous foreign antigens may provide a novel strategy to treat autoimmune diseases.
doi:10.4110/in.2014.14.1.7
PMCID: PMC3942510  PMID: 24605075
Molecular mimicry; Autoantigens; Bacterial orthologs; Granulomatosis with polyangiitis; Rheumatoid arthritis
21.  Epidural Steroid Injection in Korean Pain Physicians: A National Survey 
The Korean Journal of Pain  2013;27(1):35-42.
Background
Epidural steroid injection (ESI) is one of the most common procedures for patients presenting low back pain and radiculopathy. However, there is no clear consensus on what constitutes appropriate steroid use for ESIs. To investigate optimal steroid injection methods for ESIs, surveys were sent to all academic pain centers and selected private practices in Korea via e-mail.
Methods
Among 173 pain centers which requested the public health insurance reimbursements for their ESIs and were enrolled in the Korean Pain Society, 122 completed questionnaires were returned, for a rate of 70.5%; also returned were surveys from 39 academic programs and 85 private practices with response rates of 83.0% and 65.9%, respectively.
Results
More than half (55%) of Korean pain physicians used dexamethasone for ESIs. The minimum interval of subsequent ESIs at the academic institutions (3.1 weeks) and the private practices (2.1 weeks) were statistically different (P = 0.01).
Conclusions
Although there was a wide range of variation, there were no significant differences between the academic institutions and the private practices in terms of the types and single doses of steroids for ESIs, the annual dose of steroids, or the limitations of doses in the event of diabetes, with the exception of the minimum interval before the subsequent ESI.
doi:10.3344/kjp.2014.27.1.35
PMCID: PMC3903799  PMID: 24478899
dexamethasone; dose; epidural; radiculopathy; spinal pain; steroid; survey; triamcinolone
22.  Risk Factors for Suicidal Ideation among Patients with Complex Regional Pain Syndrome 
Psychiatry Investigation  2013;11(1):32-38.
Objective
Chronic pain frequently coexists with psychiatric symptoms in patients diagnosed with complex regional pain syndrome (CRPS). Previous studies have shown a relationship between CRPS and the risk of suicide. The purpose of this study was to assess risk factors for suicidal ideation in patients with CRPS.
Methods
Based on criteria established by the International Association for the Study of Pain, 39 patients diagnosed with CRPS Type 1 or Type 2 were enrolled in this study. Suicidal ideation was assessed using item 3 of the Hamilton Depression Rating Scale (HAMD), and symptoms of pain were evaluated using the short form of the McGill Pain Questionnaire (SF-MPQ). Psychiatric symptoms were assessed in using the Structured Clinical Interview for DSM-IV Disorders (SCID-I, SCID-II), the HAMD, the Hamilton Anxiety Rating Scale (HAMA), the Global Assessment of Functioning Scale (GAF), and the Pittsburgh Sleep Quality Index (PSQI).
Results
Twenty-nine patients (74.4%) were at high risk and 10 (25.6%) were at low risk for suicidal ideation. Risk factors significantly associated with suicidal ideation included depression (p=0.002), severity of pain (p=0.024), and low scores on the GAF (p=0.027). No significant correlations were found between suicidal ideation and anxiety or quality of sleep.
Conclusion
Significant risk factors for suicidal ideation in patients with CRPS include severity of pain, depressive symptoms, and decreased functioning. These results suggest that psychiatric evaluation and intervention should be included in the treatment of CRPS.
doi:10.4306/pi.2014.11.1.32
PMCID: PMC3942549  PMID: 24605121
Complex regional pain syndrome; Depression; Anxiety; Suicidal ideation
23.  Tacrolimus Decreases Albuminuria in Patients with IgA Nephropathy and Normal Blood Pressure: A Double-Blind Randomized Controlled Trial of Efficacy of Tacrolimus on IgA Nephropathy 
PLoS ONE  2013;8(8):e71545.
Background
Treatment remains uncertain for IgA nephropathy patients with mild to moderate proteinuria, for whom anti-hypertensive medication or the RAS blocker is not applicable due to low blood pressure.
Trial design
A double blinded randomized trial.
Methods
The anti-proteinuric effect of tacrolimus was explored for 40 biopsy-proven mild IgA nephropathies for 16 weeks. We randomly assigned patients either to receive tacrolimus or placebo with stratification by using a renin angiotensin system blocker. The primary outcome was the percentage change of final UACR compared to the baseline value (pcUACR).
Results
The mean value of pcUACR at 12-week and 16-week visits (primary outcome) was decreased more in the Tac group compared to the control group (–52.0±26.4 vs –17.3±29.3%, p = 0.001). At each visit, pcUACR was also decreased more in the Tac group compared to the control group. In the Tac group, the pcUACRs were –60.2±28.2%, –62.2±33.9%, –48.5±29.8%, and –55.5±24.0%, and, in the control group, –6.8±32.2%, –2.5±35.9%, –12.7±34.2%, and –21.9±30.6%, at 4-week, 8-week, 12-week, and 16-week visits, respectively. The pre-defined secondary outcomes were better in the Tac group compared to the control group. The frequency of decrease in pcUACR and percentage change of UPCR (pcUPCR) ≥50% at 16 weeks were 65.0% (13/20) and 55.0% (11/20)in the Tac group, and 25.0% (5/20) and 15.0% (3/20), in the control group, respectively (p = 0.025 for pcUACR and p = 0.019 for pcUPCR). However, tacrolimus wasn't effective with a dose of 0.05 mg/kg/day in patients taking ARB. The adverse events were tolerable.
Conclusion
Tacrolimus effectively reduced proteinuria in IgA nephropathy with normal blood pressure. This suggested that tacrolimus could be an alternative to corticosteroid and RAS blocker for IgA nephropathy patients who cannot endure anti-hypertensive medication.
Trial Registration
Clinicaltrial.gov NCT1224028
doi:10.1371/journal.pone.0071545
PMCID: PMC3747236  PMID: 23977072
24.  FcγRIIb mediates amyloid-β neurotoxicity and memory impairment in Alzheimer’s disease 
The Journal of Clinical Investigation  2013;123(7):2791-2802.
Amyloid-β (Aβ) induces neuronal loss and cognitive deficits and is believed to be a prominent cause of Alzheimer’s disease (AD); however, the cellular pathology of the disease is not fully understood. Here, we report that IgG Fcγ receptor II-b (FcγRIIb) mediates Aβ neurotoxicity and neurodegeneration. We found that FcγRIIb is significantly upregulated in the hippocampus of AD brains and neuronal cells exposed to synthetic Aβ. Neuronal FcγRIIb activated ER stress and caspase-12, and Fcgr2b KO primary neurons were resistant to synthetic Aβ-induced cell death in vitro. Fcgr2b deficiency ameliorated Aβ-induced inhibition of long-term potentiation and inhibited the reduction of synaptic density by naturally secreted Aβ. Moreover, genetic depletion of Fcgr2b rescued memory impairments in an AD mouse model. To determine the mechanism of action of FcγRIIb in Aβ neurotoxicity, we demonstrated that soluble Aβ oligomers interact with FcγRIIb in vitro and in AD brains, and that inhibition of their interaction blocks synthetic Aβ neurotoxicity. We conclude that FcγRIIb has an aberrant, but essential, role in Aβ-mediated neuronal dysfunction.
doi:10.1172/JCI66827
PMCID: PMC3696552  PMID: 23921129
25.  Scrambler Therapy for Patients with Cancer Pain - Case Series - 
The Korean Journal of Pain  2013;26(1):65-71.
More than 80% of cancer patients experience cancer pain. Among them, more than 50% experience moderate to severe pain. To control cancer pain, a variety of methods have been used, including medications and nerve blocks. In some patients, however, it is impossible to perform nerve blocks due to caner metastasis into the epidural space, while in other patients, opioid dose escalation is impossible due to opioid side effects; thus, cancer pain management is difficult. Scrambler therapy is a novel approach for pain control that uses EKG-like pads, which are applied above and below the site of pain. Scrambler therapy synthesizes 16 different types of nerve action potentials that provide "non-pain" information via cutaneous nerves. The advantages of this treatment are that it is non-invasive and safe and has no significant side effects. In this case series, we report the treatment results of using scrambler therapy in three cancer patients with intractable pain.
doi:10.3344/kjp.2013.26.1.65
PMCID: PMC3546214  PMID: 23342211
cancer; electric stimulation/methods; intractable; pain; scrambler therapy

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