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Peripheral neuropathy is one of the most common complications of both type 1 and type 2 diabetes. The most common diabetic neuropathy (DN) is distal symmetric polyneuropathy, with characteristic glove- and stocking-like presentation of distal sensory or motor function loss. Because painful DN is associated with increased mortality and morbidity, early recognition and preventive measures are essential. Nevertheless, diagnosing DN or painful DN is challenging, particularly in patients with early and mild neuropathy, and there is no established gold standard. Furthermore, there is no established DN treatment other than improved glycemic control, and only symptomatic management is available for painful DN. However, thanks to health-conscious living, almost one-third of patients with painful DN derive sufficient pain relief with existing pharmacotherapies. These include antidepressants (tricyclic acid, serotonin-norepinephrine reuptake inhibitor), anticonvulsants (calcium-channel blocker, sodium channel blocker), and others (sarpogrelate). A more precise and distinct symptom profile from patients with painful DN may help identify patients more responsive to one treatment versus another. In addition to pharmacological, physical, cognitive, or educational management for painful DN, large randomized clinical trials are needed to identify the most effective minimally invasive interventions. Transcutaneous electrical nerve stimulation, pain scrambler therapy, sympathetic ganglion block, and botulinum toxin injections have been investigated as alternative therapeutic outcomes.

BackgroundKetamine infusions are frequently employed for refractory complex regional pain syndrome (CRPS), but there are limited data on factors associated with treatment response. Sympathetic blocks are also commonly employed in CRPS for diagnostic and therapeutic purposes and generally precede ketamine infusions.ObjectivesWe sought to determine whether demographic and clinical factors, and technical and psychophysical characteristics of sympathetic blocks are associated with response to ketamine infusion.MethodsIn this multi-center retrospective study, 71 patients who underwent sympathetic blocks followed by ketamine infusions at 4 hospitals were evaluated. Sympathetically maintained pain (SMP) was defined as ≥ 50% immediate pain relief after sympathetic block and a positive response to ketamine was defined as ≥ 30% pain relief lasting over 3 weeks.ResultsFactors associated with a positive response to ketamine in univariable analysis were the presence of SMP (61.0% success rate vs 26.7% in those with sympathetically independent pain; P = .009) and post-block temperature increase (5.66 ± 4.20 in ketamine responders vs 3.68 ± 3.85 in non-responders; P = .043). No psychiatric factor was associated with ketamine response. In multivariable analysis, SMP (OR 6.54 [95% CI 1.83, 23.44]) and obesity (OR 8.75 [95% 1.45, 52.73]) were associated with a positive ketamine infusion outcome.ConclusionsThe response to sympathetic blocks may predict response to ketamine infusion in CRPS patients, with alleviation of the affective component of pain and predilection to a positive placebo effect being possible explanations.

Objective To compare the clinical effectiveness of sodium polynucleotide, classic hyaluronic acid, and crosslinked hyaluronic acid for the management of painful knee osteoarthritis. Design Randomized, double-blind, parallel-group clinical trial. Setting Multicenter study. Subjects Patients with chronic painful knee osteoarthritis. Methods Ninety patients were selected and randomized into polynucleotide, classic hyaluronic acid, and crosslinked hyaluronic acid groups (30 per group). Intra-articular injections of the viscosupplement for each group were administered to the patients three times at one-week intervals. The primary outcome was differences in changes of weight-bearing pain scores at 16 weeks between the groups. The secondary outcomes were changes in the intensity of knee pain during weight-bearing, walking, and rest, and functional disability, quality of life, and adverse events during the 16-week follow-up period. Results At 16 weeks, the polynucleotide group showed a higher reduction in pain score using a Visual Analog Scale score (0–100) than the classic hyaluronic acid (−17.6 [95% CI = −35.1 to −0.1]; P = .048) and crosslinked hyaluronic acid (−22.4 [95% CI = −41.5 to −3.3]; P = .016) groups. The polynucleotide and crosslinked hyaluronic acid groups showed an early-onset reduction in knee pain during weight-bearing, walking, and rest. All three groups showed reductions in functional disability and improved quality of life at 16 weeks without inter-group differences. No severe adverse events were reported throughout the study period. Conclusion Polynucleotide significantly relieves pain more and relieves pain faster in patients with knee osteoarthritis than classic and crosslinked hyaluronic acid, with improved health-related quality of life.

Acromioclavicular joint (ACJ) space narrowing has been considered to be an important diagnostic image parameter of ACJ osteoarthritis (ACJO). However, the morphology of the ACJ space is irregular because of osteophyte formation, subchondral irregularity, capsular distention, sclerosis, and erosion. Therefore, we created the ACJ cross-sectional area (ACJCSA) as a new diagnostic image parameter to assess the irregular morphologic changes of the ACJ.To hypothesize that the ACJCSA is a new diagnostic image parameter for ACJO.ACJ samples were obtained from 35 patients with ACJO and 30 healthy individuals who underwent shoulder magnetic resonance (S-MR) imaging that revealed no evidence of ACJO. Oblique coronal, T2-weighted, fat-suppressed S-MR images were acquired at the ACJ level from the two groups. We measured the ACJCSA and the ACJ space width (ACJSW) at the ACJ on the S-MR images using our imaging analysis program. The ACJCSA was measured as the cross-sectional area of the ACJ. The ACJSW was measured as the narrowest point between the acromion and the clavicle.The average ACJCSA was 39.88 ± 10.60 mmThe optimal ACJSW cutoff score was 2.37 mm, with 88.6% sensitivity and 96.7% specificity. Even though both the ACJCSA and ACJSW were significantly associated with ACJO, the ACJCSA was a more sensitive diagnostic image parameter.

Background The present study was designed to test the hypothesis that botulinum toxin would prolong the duration of a lumbar sympathetic block measured through a sustained increase in skin temperature. The authors performed a randomized, double-blind, controlled trial to investigate the clinical outcome of botulinum toxin type A for lumbar sympathetic ganglion block in patients with complex regional pain syndrome. Methods Lumbar sympathetic ganglion block was conducted in patients with lower-extremity complex regional pain syndrome using 75 IU of botulinum toxin type A (botulinum toxin group) and local anesthetic (control group). The primary outcome was the change in the relative temperature difference on the blocked sole compared with the contralateral sole at 1 postoperative month. The secondary outcomes were the 3-month changes in relative temperature differences, as well as the pain intensity changes. Results A total of 48 participants (N = 24/group) were randomly assigned. The change in relative temperature increase was higher in the botulinum toxin group than in the control group (1.0°C ± 1.3 vs. 0.1°C ± 0.8, respectively; difference: 0.9°C [95% CI, 0.3 to 1.5]; P = 0.006), which was maintained at 3 months (1.1°C ± 0.8 vs. –0.2°C ± 1.2, respectively; P = 0.009). Moreover, pain intensity was greatly reduced in the botulinum toxin group compared with the control group at 1 month (–2.2 ± 1.0 vs. –1.0 ± 1.6, respectively; P = 0.003) and 3 months (–2.0 ± 1.0 vs. –0.6 ± 1.6, respectively; P = 0.003). There were no severe adverse events pertinent to botulinum toxin injection. Conclusions In patients with complex regional pain syndrome, lumbar sympathetic ganglion block using botulinum toxin type A increased the temperature of the affected foot for 3 months and also reduced the pain. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

This Practice Advisory presents a comprehensive and evidence-based set of position statements and recommendations for the use of contrast media in interventional pain procedures. The advisory was established by an international panel of experts under the auspices of 11 multinational and multispecialty organizations based on a comprehensive review of the literature up to December 31, 2019. The advisory discusses the risks of using gadolinium-based contrast agents. These include nephrogenic systemic fibrosis, gadolinium brain deposition/retention, and encephalopathy and death after an unintentional intrathecal gadolinium injection. The advisory provides recommendations on the selection of a specific gadolinium-based contrast agent in patients with renal insufficiency, those who had multiple gadolinium-enhanced magnetic resonance imaging examinations, and in cases of paraspinal injections. Additionally, recommendations are made for patients who have a history of mild, moderate, or severe hypersensitivity reactions to contrast medium.

Neuromodulation is an expanding area of pain medicine that incorporates an array of non-invasive, minimally invasive, and surgical electrical therapies. In this Series paper, we focus on spinal cord stimulation (SCS) therapies discussed within the framework of other invasive, minimally invasive, and non-invasive neuromodulation therapies. These therapies include deep brain and motor cortex stimulation, peripheral nerve stimulation, and the non-invasive treatments of repetitive transcranial magnetic stimulation, transcranial direct current stimulation, and transcutaneous electrical nerve stimulation. SCS methods with electrical variables that differ from traditional SCS have been approved. Although methods devoid of paraesthesias (eg, high frequency) should theoretically allow for placebo-controlled trials, few have been done. There is low-to-moderate quality evidence that SCS is superior to reoperation or conventional medical management for failed back surgery syndrome, and conflicting evidence as to the superiority of traditional SCS over sham stimulation or between different SCS modalities. Peripheral nerve stimulation technologies have also undergone rapid development and become less invasive, including many that are placed percutaneously. There is low-to-moderate quality evidence that peripheral nerve stimulation is effective for neuropathic pain in an extremity, low quality evidence that it is effective for back pain with or without leg pain, and conflicting evidence that it can prevent migraines. In the USA and many areas in Europe, deep brain and motor cortex stimulation are not approved for chronic pain, but are used off-label for refractory cases. Overall, there is mixed evidence supporting brain stimulation, with most sham-controlled trials yielding negative findings. Regarding non-invasive modalities, there is moderate quality evidence that repetitive transcranial magnetic stimulation does not provide meaningful benefit for chronic pain in general, but conflicting evidence regarding pain relief for neuropathic pain and headaches. For transcranial direct current stimulation, there is low-quality evidence supporting its benefit for chronic pain, but conflicting evidence regarding a small treatment effect for neuropathic pain and headaches. For transcutaneous electrical nerve stimulation, there is low-quality evidence that it is superior to sham or no treatment for neuropathic pain, but conflicting evidence for non-neuropathic pain. Future research should focus on better evaluating the short-term and long-term effectiveness of all neuromodulation modalities and whether they decrease health-care use, and on refining selection criteria and treatment variables.

Objectives To determine the prevalence and breakdown of pain symptoms among patients with coronavirus disease 2019 (COVID-19) infection admitted for nonpain symptoms and the association between the presence of pain and intensive care unit (ICU) admission and death. Patients and Methods In this multicenter prospective study, data on the intensity and type of pain were collected on 169 patients with active severe acute respiratory syndrome coronavirus 2 infection at 2 teaching hospitals in the United States and Korea and on 8 patients with acute pain at another large teaching hospital between February 1, 2020, and June 15, 2020. Results Sixty-five of 169 patients (38.5%) reported an active pain condition. Among the 73 patients with pain, the most common pain symptoms were headache (n=22; 30.1%), chest pain (n=17; 23.3%), spinal pain (n=18; 24.7%), myalgia (n=13; 17.8%), abdominal or pelvic pain (n=13; 17.8%), arthralgia (n=11; 15.1%), and generalized pain (n=9; 12.3%). Those reporting headache as their main symptom were less likely to require ICU admission (P=.003). Acetaminophen or nonsteroidal anti-inflammatory drugs were prescribed to 80.8% (n=59), opioids to 17.8% (n=13), adjuvants to 8.2% (n=6), and ketamine to 5.5% (n=4) of patients with pain. When age 65 years and older and sex were controlled for in multivariable analysis, the absence of pain was associated with ICU admission (odds ratio, 2.92; 95% CI, 1.42 to 6.28; P=.004) and death (odds ratio, 3.49; 95% CI, 1.40 to 9.76; P=.01). Conclusion Acute pain is common during active COVID-19 infection with the most common manifestations being headache, chest pain and spine pain. Individuals without pain were more likely to require intensive care and expire than those with pain. Reasons why pain may be associated with reduced mortality include that an intense systemic stimulus (eg, respiratory distress) might distract pain perception or that the catecholamine surge associated with severe respiratory distress might attenuate nociceptive signaling.

Purpose Ultrasound-guided thoracic paravertebral block (US-TPVB) is considered a treatment option for the management of acute pain in various pain-related conditions. We conducted a prospective pilot study to evaluate the possibility of US-TPVB as a sympathetic blockade in patients with neuropathic pain disorders in the upper extremities. Patients and Methods A total of 12 patients underwent US-TPVB between the T2 and T3 paravertebral space with 10 mL of 1% mepivacaine. The temperature change (°C) before and after the procedure was compared between the ipsilateral and contralateral hands. We counted the proportion of patients showing a temperature increase ≥1.5°C and compared a change in the pain intensity before and after the procedure. Results The median increase in the temperature change between the ipsilateral and contralateral hands was 1.54°C (interquartile range, 1.28–2.20). There were seven patients (58.3%) who showed a temperature difference ≥1.5°C between both hands after the US-TPVB. Eleven patients (91.7%) reported a reduction in pain according to the score on the 11-point numerical rating scale. No serious complications relevant to the procedure were reported. Conclusion US-TPVB could be a useful technique for sympathetic blockade in patients with upper extremity pain.

Objective To investigate the opioid consumption and the healthcare resource utilization in patients with the intrathecal drug delivery system (IDDS) therapy and the comprehensive medical management (CMM) alone. Design A retrospective cohort study with a customized claims database. Setting In a university-based hospital. Subjects Patients with complex regional pain syndrome, post-laminectomy syndrome, and fibromyalgia. Methods Using propensity score matching (1:3), we selected patients with morphine infusion through IDDS (IDDS group) and CMM alone (CMM group). The primary endpoints were comparisons of average morphine equivalents daily dosages (MEDD, mg/day) for 6 and 12 months from an index date. The number of emergency room (ER) visits and hospitalizations and the total medical expenditures were compared as secondary outcomes. Results In total, 82 patients (N = 23 in the IDDS group and N = 59 in the CMM group) were analyzed. Although a 6-month average MEDD did not reach statistical significance, a 12-month average MEDD was significantly decreased in the IDDS group compared to the CMM group (53.2 ± 46.3 vs 123.9 ± 176.4, respectively; P = 0.008). ER visits were more frequent in the IDDS group than the CMM group at baseline (5.4 vs 0.5, respectively; P = .002), which was maintained for 12 months (P Conclusions The combined IDDS therapy had some benefits in reducing opioid consumption for 1-year follow-up compared to the CMM alone in chronic noncancer pain patients.

Background The past two decades have witnessed a surge in the use of cervical spine joint procedures including joint injections, nerve blocks and radiofrequency ablation to treat chronic neck pain, yet many aspects of the procedures remain controversial. Methods In August 2020, the American Society of Regional Anesthesia and Pain Medicine and the American Academy of Pain Medicine approved and charged the Cervical Joint Working Group to develop neck pain guidelines. Eighteen stakeholder societies were identified, and formal request-for-participation and member nomination letters were sent to those organizations. Participating entities selected panel members and an ad hoc steering committee selected preliminary questions, which were then revised by the full committee. Each question was assigned to a module composed of 4–5 members, who worked with the Subcommittee Lead and the Committee Chairs on preliminary versions, which were sent to the full committee after revisions. We used a modified Delphi method whereby the questions were sent to the committee en bloc and comments were returned in a non-blinded fashion to the Chairs, who incorporated the comments and sent out revised versions until consensus was reached. Before commencing, it was agreed that a recommendation would be noted with >50% agreement among committee members, but a consensus recommendation would require ≥75% agreement. Results Twenty questions were selected, with 100% consensus achieved in committee on 17 topics. Among participating organizations, 14 of 15 that voted approved or supported the guidelines en bloc, with 14 questions being approved with no dissensions or abstentions. Specific questions addressed included the value of clinical presentation and imaging in selecting patients for procedures, whether conservative treatment should be used before injections, whether imaging is necessary for blocks, diagnostic and prognostic value of medial branch blocks and intra-articular joint injections, the effects of sedation and injectate volume on validity, whether facet blocks have therapeutic value, what the ideal cut-off value is for designating a block as positive, how many blocks should be performed before radiofrequency ablation, the orientation of electrodes, whether larger lesions translate into higher success rates, whether stimulation should be used before radiofrequency ablation, how best to mitigate complication risks, if different standards should be applied to clinical practice and trials, and the indications for repeating radiofrequency ablation. Conclusions Cervical medial branch radiofrequency ablation may provide benefit to well-selected individuals, with medial branch blocks being more predictive than intra-articular injections. More stringent selection criteria are likely to improve denervation outcomes, but at the expense of false-negatives (ie, lower overall success rate). Clinical trials should be tailored based on objectives, and selection criteria for some may be more stringent than what is ideal in clinical practice.

BackgroundThe past two decades have witnessed a surge in the use of lumbar facet blocks and radiofrequency ablation (RFA) to treat low back pain (LBP), yet nearly all aspects of the procedures remain controversial.MethodsAfter approval by the Board of Directors of the American Society of Regional Anesthesia and Pain Medicine, letters were sent to a dozen pain societies, as well as representatives from the US Departments of Veterans Affairs and Defense. A steering committee was convened to select preliminary questions, which were revised by the full committee. Questions were assigned to 4–5 person modules, who worked with the Subcommittee Lead and Committee Chair on preliminary versions, which were sent to the full committee. We used a modified Delphi method, whereby the questions were sent to the committee en bloc and comments were returned in a non-blinded fashion to the Chair, who incorporated the comments and sent out revised versions until consensus was reached.Results17 questions were selected for guideline development, with 100% consensus achieved by committee members on all topics. All societies except for one approved every recommendation, with one society dissenting on two questions (number of blocks and cut-off for a positive block before RFA), but approving the document. Specific questions that were addressed included the value of history and physical examination in selecting patients for blocks, the value of imaging in patient selection, whether conservative treatment should be used before injections, whether imaging is necessary for block performance, the diagnostic and prognostic value of medial branch blocks (MBB) and intra-articular (IA) injections, the effects of sedation and injectate volume on validity, whether facet blocks have therapeutic value, what the ideal cut-off value is for a prognostic block, how many blocks should be performed before RFA, how electrodes should be oriented, the evidence for larger lesions, whether stimulation should be used before RFA, ways to mitigate complications, if different standards should be applied to clinical practice and clinical trials and the evidence for repeating RFA (see table 12 for summary).ConclusionsLumbar medial branch RFA may provide benefit to well-selected individuals, with MBB being more predictive than IA injections. More stringent selection criteria are likely to improve denervation outcomes, but at the expense of more false-negatives. Clinical trials should be tailored based on objectives, and selection criteria for some may be more stringent than what is ideal in clinical practice.

Background: The aim of this study was to investigate the clinical characteristics of complex regional pain syndrome (CRPS) in young male patients in South Korea, especially focusing on the association with military service. Methods: From January 2007 to May 2017, we investigated the electronic medical records of 430 consecutive patients, aged 18 to 30 years, who visited Seoul National University Hospital Pain Center, with a suspected diagnosis of CRPS at the initial visit. The following patient details were available for analysis: demographic and disease-related variables, relevance to military service, medications, and the treatment modalities received. Results: Out of 430 patients, 245 (57.0%) were diagnosed with CRPS, of which, 200 were male patients and 45 were female patients. Of the male patients, 95 (47.5%) developed CRPS during military service. CRPS during military service was more likely to result from sprain/strain, and the incidence of CRPS was significantly higher in the lower extremities in patients from the military service group than in those from the non-military service group. During the follow-up period, 37.9% of male CRPS patients (n = 61/161) were treated successfully. Patients with moderate to severe initial pain intensity, and diagnosed during their military service, showed better outcomes. Conclusions: Our results demonstrated that manifestation of CRPS in the young Korean population was more common in male and among those male CRPS patients, about half the cases developed during the military service period.

Objective We investigated the thoracic segment corresponding to the inferior margin of the rhomboid major muscle (RMM) using ultrasound (US) to evaluate its potential as a reliable anatomic landmark for segment identification. Design A prospective observational study. Setting An operating room. Subjects Patients who underwent procedures around the thoracic spine. Methods Four hundred segments corresponding to the RMM’s inferior margin were identified through the use of paravertebral sagittal US and confirmed by fluoroscopy in 100 participants in the prone position with upward and downward shoulder rotation, comprising four datasets (up-right, up-left, down-right, and down-left). The US identification of the RMM’s inferior margin was dichotomously scored (clear vs ambiguous). Each dataset was divided into two groups (dominant segment group vs remaining segments group), which were compared. Factors relevant to the dominant segment associated with the RMM’s inferior border were determined through univariable analyses. Results The T6 segment was observed most commonly (59.5%) along the RMM’s inferior border on paravertebral sagittal US acquired in the prone position, followed by T5 (25.0%), T7 (12.8%), and T4 (2.7%). The segments corresponding to the RMM remained unchanged by shoulder posture in most participants (n = 74, 74%). The RMM’s inferior border was clearly distinguishable in 330 cases (82.5%). When the RMM’s inferior border was clearly identified, the corresponding segment was likely to match T6 in all datasets, with odds ratios ranging from 3.24 to 6.2. Conclusions The RMM’s inferior border over the transverse process corresponded to T6 most frequently on paravertebral sagittal US, and its deep fascia was clearly visible in most cases.

Background Deep spinal infection is a devastating complication after epidural injection. This study aimed to investigate the incidence of deep spinal infection primarily after outpatient single-shot epidural injection for pain. Secondarily, this study assessed the national trends of the procedure and risk factors for said infection. Methods Using South Korea’s National Health Insurance Service sample cohort database, the 10-yr national trend of single-shot epidural injections for pain and the incidence rate of deep spinal infection after the procedure with its risk factors were determined. New-onset deep spinal infections were defined as those occurring within 90 days of the most recent outpatient single-shot epidural injection for pain, needing hospitalization for at least 1 night, and receiving at least a 4-week course of antibiotics. Results The number of outpatient single-shot epidural injections per 1,000 persons in pain practice doubled from 40.8 in 2006 to 84.4 in 2015 in South Korea. Among the 501,509 injections performed between 2007 and 2015, 52 cases of deep spinal infections were detected within 90 days postprocedurally (0.01% per injection). In multivariable analysis, age of 65 yr or more (odds ratio, 2.91; 95% CI, 1.62 to 5.5; P = 0.001), living in a rural area (odds ratio, 2.85; 95% CI, 1.57 to 5.0; P < 0.001), complicated diabetes (odds ratio, 3.18; 95% CI, 1.30 to 6.7; P = 0.005), multiple epidural injections (three times or more) within the previous 90 days (odds ratio, 2.34; 95% CI, 1.22 to 4.2; P = 0.007), and recent use of immunosuppressants (odds ratio, 2.90; 95% CI, 1.00 to 6.7; P = 0.025) were significant risk factors of the infection postprocedurally. Conclusions The incidence of deep spinal infection after outpatient single-shot epidural injections for pain is very rare within 90 days of the procedure (0.01%). The data identify high-risk patients and procedure characteristics that may inform healthcare provider decision-making. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

Background As national opioid consumption in South Korea has soared, well-validated screening tools for opioid use disorder (OUD) have become indispensable. The aims of our study were to evaluate OUD using the Korean version of the CAGE-Adapted to Include Drugs (CAGE-AID) and the CAGE-Opioid (an alternative version of the CAGE-AID), and to investigate clinical predictors that might be useful to screen for OUD in conjunction with the CAGE-AID/Opioid questionnaires. Methods A single-center, prospective, observational study was performed. After linguistic validation of the Korean version of the CAGE-AID/Opioid questionnaires, we assessed OUD in patients with chronic opioid treatment. Multivariable logistic models of the CAGE-AID/Opioid questionnaires combined with relevant clinical predictors were established. Then, the receiver operating characteristic curve analysis of the multivariable CAGE-AID/Opioid models was conducted to assess diagnostic accuracy to screen for OUD. Next, we calculated predicted probability with >85% sensitivity and >50% specificity in each CAGE-AID and CAGE-Opioid model. Using the optimal value of the predicted probability, a cutoff score of the CAGE-AID/Opioid questionnaires combined with the relevant clinical factors was suggested to screen for OUD. Results Among 201 participants, 51 patients showed ≥1 OUDs. In the multivariable regression model, male sex, comorbid neuropsychiatric disorder, and current heavy drinking significantly remained as clinical variables to predict OUD combined with the scores of the Korean CAGE-AID/Opioid questionnaire. The area under the curve was 0.77 (95% confidence interval, 0.71-0.83) for the CAGE-AID model and 0.78 (95% confidence interval, 0.71-0.83) for the CAGE-Opioid model. The optimal predicted probability values to screen for OUD in the CAGE-AID/Opioid models were >0.135 (sensitivity, 0.86; specificity, 0.52) and >0.142 (sensitivity, 0.86; specificity, 0.53), respectively. When we used these predictive probabilities, the cutoff score of the CAGE-AID/Opioid questionnaires ranged from 0 to 3, which was dependent on the presence of the relevant clinical variables in each model. Conclusions In this study, one fourth of the total participants with chronic opioid treatment showed OUD in the Korean population. The multivariable models of the CAGE-AID/Opioid with sex, comorbid neuropsychiatric disorder, and current heavy drinking are valid parameters to screen for OUD, with the cutoff scores of the CAGE-AID/Opioid questionnaires ranging from 0 to 3 depending on the presence of the clinical variables.

The aim of this study was to investigate distinct neurometabolites in the right and left thalamus and insula of patients with complex regional pain syndrome (CRPS) compared with healthy controls using proton magnetic resonance spectroscopy. Levels of N-acetylaspartate (NAA), N-acetylaspartylglutamate (NAAG), myo-inositol (ml), glutamine (Gln), glycerophosphocholine (GPC), glutathione (GSH), and alanine (Ala) relative to total creatine (tCr) levels, including creatine and phosphocreatine, were determined in the right and left thalamus and insula in 12 patients with CRPS compared with 11 healthy controls using magnetic resonance spectroscopy. Levels of NAAG/tCr and Ala/tCr were higher in patients with CRPS than in controls in the left thalamus. NAAG/tCr, ml/tCr, and Gln/tCr levels were higher but NAA/tCr levels were lower in the right insula of patients with CRPS compared with controls. There were negative correlations between GSH/tCr and pain score (McGill Pain Questionnaire) in the left thalamus. These findings are paramount to understand and determine all aspects of the complex pathophysiological mechanisms that underlie CRPS, including involvement of the central and parasympathetic nervous systems as well as oxidative stress and antioxidants. Thus, the distinct metabolites presented herein may be essential to understand a strong diagnostic and prognostic potential for CRPS and to develop effective medical treatments.

Objective: Although the clinical features and pathophysiology of complex regional pain syndrome (CRPS) have been studied in the peripheral and central nervous systems, few plausible pathological interactions are known among the metabolites in these systems. Thus, the purpose of this study was to investigate abnormal relationships and interactions between peripheral metabolites and central neurometabolites in patients with CRPS. Methods: Various metabolites and molecules were measured in the peripheral blood, and central neurometabolites in the right and left thalamus using proton magnetic resonance spectroscopy in 12 patients with CRPS and 11 healthy controls. Interactions between peripheral metabolites in blood and central neurometabolites in the right and left thalamus were also investigated. Results: The interactions between peripheral and central metabolites were different in the right and left hemispheres of healthy subjects, suggesting the presence of right hemisphere-dependent energy homeostasis and left hemisphere-dependent acid-base homeostasis that enables effective functioning. The interactions between central and peripheral metabolites in CRPS patients were distinct from those in healthy individuals, supporting the possibility of abnormal interactions and disrupted homeostasis between peripheral and central metabolites, which may result from neuroinflammation and immune system dysfunction. Conclusion: To the authors’ knowledge, this is the first report describing abnormal metabolic dysfunction and disrupted homeostasis in interactions between metabolites of the peripheral and central nervous systems in CRPS. The approach used to uncover hidden pathophysiologies will improve understanding of how chronic pain can disrupt homeostasis in interactions between two systems and how alternative metabolites can be activated to recover and compensate for pathological dysfunctions in patients with CRPS.

High-intensity focused ultrasound (HIFU) is a noninvasive thermodestructive procedure targeting internal organs with concentrated sonification energy that may cause pain. We aimed to compare the effectiveness of epidural analgesia (EA) and monitored anesthesia care (MAC) in HIFU treatment of uterine adenomyosis.Sixty-eight patients were included in this case-control study. Thirty-seven patients underwent MAC; 31 patients underwent fluoroscope-guided epidural analgesia. The primary outcome was a frequency of patients reporting severe or very severe intraoperative pain. Secondary outcomes were differences in dosages of analgesics, ablation ratio, and other clinical factors.The EA group reported a significantly lower frequency of severe or very severe intraoperative pain than did the MAC group (41.9% vs. 75.7%; p = .006). Consumption of remifentanil during treatment was significantly lower in the EA group (173 ± 189 µg vs. 426 ± 380 µg; p = .001), as was the use of fentanyl in the recovery room (52 ± 38 µg vs. 75 ± 44 µg; p = .030). Multivariable analysis revealed EA to be the largest contributing factor to increased nonperfused volume ratio (B = 0.41; 95% confidence interval = 0.29 to 0.53; p .001). The frequency of thermal injury after HIFU was significantly lower in the EA group (22.6% vs. 54.1%; p = .008).EA during HIFU treatment of uterine adenomyosis improved quality of pain control and ablation ratio over MAC without increasing risk of treatment-related complications. EA also reduced consumption of opioid analgesics during and after HIFU treatment.

Ho-Jin Lee,1 Eunjoo Choi,1 Francis Sahngun Nahm,1 Seong-Soo Choi,2 Young-Hoon Kim,3 Jee Youn Moon,4 Shin Hyung Kim,5 Chan-Woo Cho,6 Pyung Bok Lee1,7 1Department of Anesthesiology and Pain Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea; 2Department of Anesthesiology and Pain Medicine, Asan Medical Center, Seoul, Republic of Korea; 3Department of Anesthesiology and Pain Medicine, Seoul St. Mary’s Hospital, Seoul, Republic of Korea; 4Department of Anesthesiology and Pain Medicine, Seoul National University Hospital, Seoul, Republic of Korea; 5Department of Anesthesiology and Pain Medicine, Severance Hospital, Seoul, Republic of Korea; 6Seoul Chan Pain Clinic, Seoul, Republic of Korea; 7Department of Anesthesiology and Pain Medicine, Seoul National University, Seoul, Republic of Korea Purpose: We aimed to investigate the prevalence of fibromyalgia (FM) in patients who visited outpatient pain clinics in Korea, using the modified 2010 American College of Rheumatology (ACR) criteria and to evaluate comorbid conditions that may be associated with FM.Patients and methods: Outpatients, aged ≥18 years, who first visited pain clinics at any of the 14 tertiary care university hospitals, were recruited for this study. Modified 2010 ACR criteria were used to diagnose FM. Participants’ demographic information and eleven comorbid measures (sleep disturbance, fatigue, irritable bowel syndrome, amnesia, hypothyroidism, headache, anxiety, depression, rheumatism, low back pain, and history of traffic accident) were also investigated via additional questionnaires.Results: We recruited 1,233 outpatients (754 men and 479 women). Based on the modified 2010 ACR criteria, 13.38% (165/1,233 patients, 95% CI: 11.48–15.28) of patients had FM. As participants with a history of FM were excluded, the prevalence of FM was 11.0% (123/1,118 patients). Patients with FM were more likely to have one or more of the eleven predetermined comorbid conditions. Patients who were female and who had a previous history of FM, sleep disturbance, headache, or a history of traffic accident were more likely to have FM.Conclusion: FM, according to the modified 2010 ACR criteria, appears to be a common disorder among chronic pain patients referred to tertiary care university hospital pain clinics. Therefore, physicians treating pain should consider this prevalence of FM among pain clinic patients. Keywords: tertiary care centers, chronic pain, diagnosis, fibromyalgia

Objectives. So far, dysfunction in mental rotation has been assessed in relation to the left- or right-sided CRPS. Here we examined mental rotation in patients with upper or lower limb CRPS. Considering the potential role of socio-emotional functioning on the perception of body image, we further investigated the association between performance on mental rotation and socio-emotional characteristics. Methods. We examined the performance of 36 patients with upper or lower limb CRPS on the limb laterality recognition. Accuracy and response times for pictures of hands and feet at 4 rotation angles were evaluated. Socio-emotional functioning was measured by the Interpersonal Reactivity Scale and the Toronto Alexithymia Scale. Results. Patients with upper limb pain showed longer RTs to recognize the laterality of hands than feet (P = 0.002), whereas patients with lower limb pain showed longer RTs for feet than hands (P = 0.039). Exploratory correlation analyses revealed that RTs for feet were negatively correlated with the levels of empathic ability to take another’s perspective (P = 0.006) and positively correlated with the level of emotional difficulty in identifying feelings (P = 0.006). Conclusions. This study is the first to report selectively impaired mental rotation of hands vs feet in patients with upper or lower limb CRPS. The findings suggest that impaired mental rotation derives from relative deficits in the representation of the affected limb. Correlations between impaired mental rotation and socio-emotional inability indicate that an altered body schema may be closely associated with impaired social cognitive aspects in CRPS patients.

Background: The study investigated virtual reality (VR) immersion in alleviating procedure-related pain in patients with chronic pain undergoing fluoroscopy-guided minimally-invasive intervention in a prone position at an outpatient clinic. Methods: In this prospective randomized controlled study, 38 patients undergoing lumbar sympathetic ganglion block were randomized into either the VR or the control group. In the VR group, procedure-related pain was controlled via infiltration of local anesthetics while watching a 30-minute VR hypnotic program. In the control group, the skin infiltration alone was used, with the VR device switched off. The primary endpoint was an 11-point score on the numerical rating scale, indicating procedure-related pain. Patients’ satisfaction with pain control, anxiety levels, the need for additional local anesthetics during the procedure, hemodynamic stability, and any adverse events were assessed. Results: Procedure-related pain was significantly lower in the VR group (3.7 ± 1.4) than in the control group (5.5 ± 1.7; P = 0.002). Post-procedural anxiety was lower in the VR group than in the control group (P = 0.025), with a significant reduction from pre-procedural anxiety (P < 0.001). Although patients’ satisfaction did not differ significantly (P = 0.158) between the groups, a higher number of patients required additional local anesthetics in the control group (n = 13) than in the VR group (n = 4; P = 0.001). No severe adverse events occurred in either group during the study. Conclusions: VR immersion can be safely used as a novel adjunct to reduce procedural pain and anxiety during fluoroscopic pain intervention.

Objective: To test the effectiveness of electroacupuncture (EA) for managing intractable neuropathic pain (NeP) and assess the protocol for a larger confirmatory trial. Design: A prospective, multi...

Purpose Ultrasound-guided thoracic paravertebral block (US-TPVB) is considered a treatment option for the management of acute pain in various pain-related conditions. We conducted a prospective pilot study to evaluate the possibility of US-TPVB as a sympathetic blockade in patients with neuropathic pain disorders in the upper extremities. Patients and Methods A total of 12 patients underwent US-TPVB between the T2 and T3 paravertebral space with 10 mL of 1% mepivacaine. The temperature change (°C) before and after the procedure was compared between the ipsilateral and contralateral hands. We counted the proportion of patients showing a temperature increase ≥1.5°C and compared a change in the pain intensity before and after the procedure. Results The median increase in the temperature change between the ipsilateral and contralateral hands was 1.54°C (interquartile range, 1.28–2.20). There were seven patients (58.3%) who showed a temperature difference ≥1.5°C between both hands after the US-TPVB. Eleven patients (91.7%) reported a reduction in pain according to the score on the 11-point numerical rating scale. No serious complications relevant to the procedure were reported. Conclusion US-TPVB could be a useful technique for sympathetic blockade in patients with upper extremity pain.

ObjectiveTo compare the nonadaptive manual system with the position-adaptive system in subjects with permanent spinal cord stimulator (SCS) implantation over a two-year follow-up period.DesignRetrospective study.SettingTertiary university-based national hospital.SubjectsPatients who underwent permanent SCS implantation procedures.MethodsPatients were divided into an adaptive group and a nonadaptive group according to the type of implanted SCS device. The primary outcome was the change (%) in pain intensity from baseline between the adaptive and nonadaptive groups at 24 months after SCS implantation. The secondary outcomes were comparisons of detailed clinical variables such as the scores of patient pain and satisfaction during the two-year follow-up after SCS therapy. Further, the number of subjects with SCS removal or revision within two years after SCS implantation was investigated.ResultsOf 187 patients with permanent SCS implantation, 85 in the nonadaptive group and 64 in the position-adaptive group were finally analyzed. The reduction in pain intensity at 24 months was higher in the adaptive group (−38.6%) than in the nonadaptive group (−30.8%, P = 0.05). Similarly, patient satisfaction with the SCS treatment at 24 months was superior in the adaptive group than in the nonadaptive group (85.7% vs 67.5% were satisfied in each group, respectively, P = 0.024). During the two years, 5.3% of patients (N = 10) underwent SCS removal and 7.0% (N = 13) underwent revision procedures.ConclusionsThere was a trend of a sustained reduction in pain intensity as well as improvement in patient satisfaction at two-year follow-up in the position-adaptive system, suggesting long-term benefit over the nonadaptive manual system during SCS treatment.

BackgroundWe aimed to investigate the prevalence of dysautonomia in complex regional pain syndrome (CRPS) via the combined autonomic nervous system (ANS) function tests, including the deep breathing test (DBT), orthostatic test (OST) and sympathetic skin response (SSR).MethodWe retrospectively examined 263 patients who underwent the combined ANS tests to evaluate CRPS between August 2013 and December 2016. Based on the Budapest clinical criteria, patients were stratified into confirmed-CRPS or suspected-CRPS groups. We performed binary logistic regression analysis using the inverse probability of treatment weighting to investigate the association between the tests and CRPS. Sensitivity and specificity were calculated to assess the diagnostic performance of the ANS tests for CRPS. We compared the results of these tests between the outcomes of sympathetic nerve blocks (SNBs).ResultsAmong 247 patients, finally included in this study, 199 patients (80.6%) were diagnosed with CRPS. Abnormal results of overall or each ANS function test showed significant associations with CRPS, excluding OST (overall abnormality: OR 2.44, 95% CI 1.51 to 3.95; pConclusionDysautonomia, as evaluated using the combined ANS tests, were observed in a small portion of patients with CRPS. The diagnostic performances of these tests for CRPS were inadequate for clinical purposes.

BackgroundAlthough there is a low incidence of complications associated with epidural injections, pain physicians should still remain vigilant for potentially serious adverse outcomes. This study aimed to identify and describe the major complications of epidural injections.MethodsThis retrospective, observational, medicolegal study analyzed closed cases of precedents involving complications of epidural injections from January 1997 to August 2019 using the database of the Supreme Court of Korea’s judgement system. Clinical characteristics and judgement statuses were analyzed.ResultsOf the 73 potential cases assessed for eligibility, a total of 49 malpractice cases were included in the final analysis. Thirty-three claims resulted in payments to the plaintiffs, with a median payment of US$103 828 (IQR: US$45 291–US$265 341). The most common complication was infection (n=13, 26.5%), followed by worsening pain (n=8, 16.3%). Physician malpractice before, during, and after the procedure was claimed by plaintiffs in 18 (36.7%), 44 (89.8%), and 31 (63.3%) cases, respectively. Of these cases, 6 (33.3%), 19 (43.2%), and 15 (48.4%), respectively, were adjudicated in favor of the plaintiffs by the courts. In cases involving postprocedural physician errors, the majority (13/15) of the plaintiff verdicts were related to delayed management. Violation of the physician’s duty of informed consent was claimed by plaintiffs in 31 (63.3%) cases, and 14 (45.2%) of these cases were judged medical malpractice.ConclusionsOur data will allow pain physicians to become acquainted with the major epidural injection-associated complications that underlie malpractice cases.

Background Lumbar sympathetic neurolysis (LSN) is a treatment option for complex regional pain syndrome (CRPS). We examined whether LSN-related temperature changes are associated with clinical outcome and investigated relationships between the outcome of LSN and clinical variables in patients with CRPS-I. Methods We included 95 patients with CRPS-I affecting a single lower extremity, by the Budapest criteria, and who underwent LSN after successful lumbar sympathetic blocks, in this retrospective study. Fluoroscopy-guided LSN was conducted with 1.5 mL of 99% alcohol at L2 and L3 vertebral levels. Positive outcome was defined as a reduction of ≥50% on a numeric rating scale pain score at 6 months after LSN. The relationship between successful outcome and clinical variables was analyzed. Results Positive LSN outcome occurred in 49.5% of patients, and it was suggested that Sympathetically maintained pain may accompany CRPS-I in 28% of patients. The overall temperature in the affected limb was increased after LSN, without contralateral limb temperature changes, but did not differ significantly between the positive and negative outcome groups (P = 0.590). Temperature after LSN in warm-type CRPS was reduced in the affected limb, without contralateral limb temperature changes. The absolute temperature change was significantly greater in cold-type than in warm-type CRPS (P = 0.026). In multivariate analysis, a short duration of pain and concurrent cold intolerance were significant factors predicting a positive outcome after LSN. Conclusions LSN may be effective in some patients with CRPS, irrespective of temperature changes and temperature asymmetry pattern. A short duration of pain and concurrent cold intolerance significantly predict successful LSN.

Percutaneous epidural adhesiolysis (PEA) is a minimally invasive procedure that is performed to relieve low back and/or lower limb pain secondary to adhesions or scarring in the epidural space that is refractory to conservative treatment. The optimal concentration of hypertonic saline might be an important factor in the safety and efficacy of PEA. We evaluated differences in the efficacy and safety of 2 concentrations of hypertonic saline (5% and 10%) used in lumbar PEA at our institutions in a retrospective study.Patients who received lumbar PEA between January 2009 and June 2014 at either of 2 large civilian teaching institutions in South Korea were assigned to the 5% or 10% groups according to the osmolality of saline. The primary outcome of this study was the difference in change in the 11-point numerical rating scale (NRS) scores of low back and leg pain from baseline to 6 months after PEA between patients in the 2 groups. The number of additional epidural injections, patients' satisfaction with PEA, and any complications that occurred within 6 months after PEA were reviewed.This study included 543 patients (5% group, 333; 10% group, 210). Post-PEA NRS pain scores were significantly lower compared with those at baseline in both groups; however, there were no significant differences between the 2 groups at 6 months or any time point after PEA with regard to any of the clinical characteristics, except infusion-related pain, which exhibited borderline significance for greater scores in the 10% group compared with those in the 5% group (P = .041). Multivariable linear regression analysis with adjustments for covariates, including the number of additional epidural injections, revealed no significant association between patient group and the decrease in NRS pain scores at 6 months of follow-up. Transient adverse events related to PEA were recorded in 3 patients (10% group, 2; 5% group, 1).In PEA, 5% hypertonic saline exhibited similar positive outcomes after 6 months of follow-up as 10% hypertonic saline, with less infusion-related pain. This result suggests that infusion of 5% hypertonic saline may be considered as an alternative to 10% hypertonic saline in lumbar PEA. Further prospective randomized studies are required to better appreciate the outcome with regard to the use of different concentrations of hypertonic saline for PEA.

The lumbar sympathetic ganglion block (LSGB) is widely used for diagnosing and treating sympathetically maintained pain disorders. The LSGB has been conventionally carried out under fluoroscopy or computed tomography guidance. However, as ultrasound technology improved, ultrasound-guided interventions have been expanding their territory to deeper structures. Ultrasound guidance provides many benefits including protecting vascular injection, shortening procedure time in some cases, and reducing the emission of radiation. In this report, we describe a successful case of a US-guided LSGB without major complications. We expect that US-guided LSGBs can be implemented and furnished in the daily outpatient clinical setting by highly trained pain physicians.

Background: Because it affords greater accuracy than landmark-based techniques, ultrasound guidance may reduce the volume of local anesthetic required for sympathetic blockade of the upper extremity. We hypothesized that 4 mL would provide a similar clinical effect when compared to larger volumes. Methods: One hundred and two patients with chronic neuropathic pain of the upper extremity or face were randomly assigned to receive an ultrasound-guided (USG) stellate ganglion block (SGB) with either 4 mL (group A), 6 mL (group B) or 8 mL (group C) mL of 1.0% lidocaine. Skin temperatures of the face, hand, and axillary fold were measured bilaterally at baseline, 10, 20, and 30 min after the block. Our primary outcome was the relative increase in hand temperature on the blocked side at 30 min and our non-inferiority margin was &minus, 0.6 &deg, C. Secondary outcomes included success rate (as defined by a relative temperature increase of &ge, 1.5 &deg, C), pain relief, degree of ptosis and side-effects. Results: The 95% confidence intervals for the difference of the means exceeded our non-inferiority margin (A versus B: &minus, 0.76 to 0.24, A versus C: &minus, 0.89 to 0.11) for temperature changes in the hand, however, success rates were similar (44, 45 and 55% for A, B and C respectively, p = 0.651). No intergroup differences were found in temperature-related outcomes for the other measurement sites (face, axilla). The incidence of minor side-effects was significantly higher in group C and no block-related complications were noted. Conclusions: We were unable to establish the non-inferiority of a 4 mL volume for sympathetic blockade of the hand. The clinical significance of these findings is unclear as success rates were similar between the different groups. In contrast, the 6- and 8 mL volumes were not associated with greater temperature changes in the face and axilla.

Complex regional pain syndrome (CRPS) and fibromyalgia (FM) share many features. Both can cause severe pain and are considered to have a mechanism of action, including dysfunction of the sympathetic nervous system. However, they have clinical differences in pain range and degree. The present study aimed to find neurophysiologic differences between CRPS and FM using quantitative electroencephalography (QEEG). Thirty-eight patients with CRPS and 33 patients with FM were included in the analysis. Resting-state QEEG data were grouped into frontal, central, and posterior regions to analyze for regional differences. General linear models were utilized to test for group differences in absolute and relative powers. As a result, the CRPS group relative to FM group showed lower total absolute powers in the beta band (F = 5.159, P

BackgroundAlthough the quantitative sensory axon reflex test (QSART) is used to evaluate sudomotor dysfunction in the diagnosis of complex regional pain syndrome (CRPS), its validity remains controversial. This study investigated the diagnostic performance of the QSART for CRPS and assessed associations between results of the QSART and other clinical variables.MethodsWe examined the electronic medical records of 196 consecutive patients who underwent the QSART with a suspected diagnosis of CRPS, during the period from January 2013 to December 2015. To assess the diagnostic performance of the QSART for CRPS based on the Budapest research criteria, we calculated sensitivity, specificity, positive likelihood ratio and negative likelihood ratio. Furthermore, we performed binary logistic regression analyses to investigate the relationships between QSART results and other clinical variables.ResultsThe sensitivity and specificity of the QSART for diagnosing CRPS were 67.6% and 40.6%, respectively. The OR for diagnosing CRPS using the QSART was not statistically significant (1.43; 95% CI 0.65 to 3.14; p=0.376), whereas it was for distinguishing CRPS types I and II (4.11; 95% CI 1.34 to 12.57; p=0.013). In multivariable analysis, there were no correlations between the results of the QSART and other variables, except hypertension (OR=0.34; 95% CI 0.13 to 0.91; p=0.032).ConclusionThe QSART showed low diagnostic value as a screening or a confirmatory test for CRPS according to the Budapest research criteria. CRPS type II was more likely than CRPS type I to result in abnormal QSART results.

Sedation protocols during spinal anesthesia often involve sedative drugs associated with complications. We investigated whether virtual reality (VR) distraction could be applied during endoscopic urologic surgery under spinal anesthesia and yield better satisfaction than pharmacologic sedation. VR distraction without sedative was compared with pharmacologic sedation using repeat doses of midazolam 1&ndash, 2 mg every 30 min during urologic surgery under spinal anesthesia. We compared the satisfaction of patients, surgeons, and anesthesiologists, as rated on a 5-point prespecified verbal rating scale. Two surgeons and two anesthesiologists rated the scale and an overall score was reported after discussion. Thirty-seven patients were randomized to a VR group (n = 18) or a sedation group (n = 19). The anesthesiologist&rsquo, s satisfaction score was significantly higher in the VR group than in the sedation group (median (interquartile range) 5 (5&ndash, 5) vs. 4 (4&ndash, 5), p = 0.005). The likelihood of both patients and anesthesiologists being extremely satisfied was significantly higher in the VR group than in the sedation group. Agreement between the scores for surgeons and those for anesthesiologists was very good (kappa = 0.874 and 0.944, respectively). The incidence of apnea was significantly lower in the VR group than in the sedation group (n = 1, 5.6% vs. n = 7, 36.8%, p = 0.042). The present findings suggest that VR distraction is better than drug sedation with midazolam in terms of patient&rsquo, s and anesthesiologist&rsquo, s satisfaction and avoiding the respiratory side effects of midazolam during endoscopic urologic surgery under spinal anesthesia.