Evaluation of thoracic sympathetic ganglion block as a predictor for response to ketamine infusion therapy and spinal cord stimulation in patients with chronic upper extremity pain.

OBJECTIVE: To investigate the predictive value of thoracic sympathetic ganglion block (TSGB) in response to ketamine infusion therapy (KIT) and spinal-cord stimulation (SCS) in patients with chronic upper-extremity pain including complex regional pain syndrome (CRPS). DESIGN: Retrospective. SETTING: Tertiary hospital single-center. SUBJECTS: Patients who underwent TSGB receiving KIT or SCS within a 3-year window. METHODS: Positive TSGB outcomes were defined as ≥ 2 0-10 Numerical Rating Scale (NRS) score reduction at 2 weeks post-procedure. Positive KIT and SCS outcomes were determined by ≥ 2 NRS score reduction at 2-4 weeks post-KIT and ≥4 NRS score reduction at 2-4 weeks post-SCS implantation, respectively. RESULTS: Among 207 patients who underwent TSGB, 38 received KIT and 34 underwent SCS implantation within 3 years post-TSGB; 33 patients receiving KIT and 32 patients receiving SCS were included. Among 33 patients who received KIT, 60.6% (n = 20) reported a ≥ 2 0-10 NRS pain-score reduction. Positive response to TSGB occurred in 70.0% (n = 14) KIT responders, significantly higher than that in 30.8% (n = 4) KIT non-responders. Multivariable analysis revealed a positive association between positive responses to TSGB and KIT (OR 7.004, 95% CI 1.26-39.02). Among 32 patients who underwent SCS implantation, 68.8% (n = 22) experienced short-term effectiveness. Positive response to TSGB was significantly higher in SCS responders (45.5%, n = 10) than in non-responders (0.0%). However, there were no associations between pain reduction post-TSGB and that post-KIT or post-SCS. CONCLUSIONS: A positive response to TSGB is a potential predictor for positive KIT and SCS outcomes among patients with chronic upper-extremity pain, including CRPS.

Comparison of Polynucleotide, Sodium Hyaluronate, and Crosslinked Sodium Hyaluronate for the Management of Painful Knee Osteoarthritis: A Multi-Center, Randomized, Double-Blind, Parallel-Group Study.

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.

Myth and Truth in Opioid Consumption with Intrathecal Morphine Pump Implantation in Chronic Pain: A Retrospective Cohort Study with Claims Database in South Korea.

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 < 0.001). Otherwise, the number of hospitalization and the medical expenditures for pain management were not different between the groups for 12 months. 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.

Sympathetic Blocks as a Predictor for Response to Ketamine Infusion in Patients with Complex Regional Pain Syndrome: A Multicenter Study.

BACKGROUND: Ketamine 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. OBJECTIVES: We sought to determine whether demographic and clinical factors, and technical and psychophysical characteristics of sympathetic blocks are associated with response to ketamine infusion. METHODS: In 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. RESULTS: Factors 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. CONCLUSIONS: The 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.

Neuromodulation for chronic pain.

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.

Botulinum Toxin Type A for Lumbar Sympathetic Ganglion Block in Complex Regional Pain Syndrome: A Randomized Trial.

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.

Can the Rhomboid Major Muscle Be Used to Identify the Thoracic Spinal Segment on Ultrasonography? A Prospective Observational Study.

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.

Dysfunctional energy metabolisms in fibromyalgia compared with healthy subjects.

This study aimed to investigate the levels of creatine (Cr) metabolites in the anterior cingulate cortex (ACC), thalamus, and insula of patients with fibromyalgia (FM) using proton magnetic resonance spectroscopy (MRS). The levels of Cr and phosphocreatine (PCr) relative to total Cr (tCr), which includes Cr and PCr, in the ACC, thalamus, and insula were determined using MRS in 12 patients with FM and in 13 healthy controls. The FM group had lower levels of PCr/tCr in the ACC and right insula compared to healthy controls. There was a negative correlation between Cr/tCr in the ACC and total pain levels (McGill Pain Questionnaire-Total; r = -0.579, p = 0.049) and between Cr/tCr in the left insula and affective pain levels (McGill Pain Questionnaire-Affective; r = -0.638, p = 0.047) in patients with FM. In addition, there were negative correlations between stress levels (Stress Response Inventory) and Cr/tCr in the right (r = -0.780, p = 0.005) and left thalamus (r = -0.740, p = 0.006), as well as in the right insula (r = -0.631, p = 0.028) in patients with FM. There were negative correlations between symptom levels of post-traumatic stress disorder (PTSD; PTSD checklist) and Cr/tCr in the right (r = -0.783, p = 0.004) and left thalamus (r = -0.642, p = 0.024) of patients with FM. These findings are paramount to understanding the decisive pathologies related to brain energy metabolism in patients with FM.

Abnormal neurometabolites in fibromyalgia patients: Magnetic resonance spectroscopy study.

This study aimed to investigate distinct neurometabolites in the anterior cingulate cortex (ACC), right and left thalamus, and insula of patients with fibromyalgia (FM) compared with healthy controls using proton magnetic resonance spectroscopy (MRS). Levels of N-acetylaspartate (NAA), N-acetylaspartylglutamate (NAAG), total NAA (tNAA = NAA + NAAG), myo-inositol (ml), glutamine (Gln), glutamate (Glu), Glx (Glu + Gln), glycerophosphocholine (GPC), total choline (tCho = GPC + phosphocholine) and glutathione (GSH) levels relative to total creatine (tCr) levels including creatine (Cr) and phosphocreatine (PCr) and relative to Cr levels were determined in the ACC, right and left thalamus, and insula in 12 patients with FM and 13 healthy controls using MRS. In the ACC, NAA/tCr (P = 0.028) and tCho/tCr (P = 0.047) were higher in patients with FM. In the right and left insula, tNAA/tCr (P = 0.019, P = 0.007, respectively) was lower in patients with FM. Patients with FM showed lower levels of ml/Cr (P = 0.037) in the right insula than healthy controls. These findings are paramount to understand decisive pathophysiological mechanisms related to abnormal features in the brain and parasympathetic nervous systems in FM. We suggest that the results presented herein may be essential to understand hidden pathological mechanisms and also life system potential as protective and recovering metabolic strategies in patients with FM.

Deep Spinal Infection after Outpatient Epidural Injections for Pain: A Retrospective Sample Cohort Study Using a Claims Database in South Korea.

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.

Impaired Performance in Mental Rotation of Hands and Feet and Its Association with Social Cognition in Patients with Complex Regional Pain Syndrome.

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.

Consensus practice guidelines on interventions for cervical spine (facet) joint pain from a multispecialty international working group.

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.

The Use of Contrast Agents in Interventional Pain Procedures: A Multispecialty and Multisociety Practice Advisory on Nephrogenic Systemic Fibrosis, Gadolinium Deposition in the Brain, Encephalopathy After Unintentional Intrathecal Gadolinium Injection, and Hypersensitivity Reactions.

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.

The Role of Prostaglandin E1 as a Pain Mediator through Facilitation of Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel 2 via the EP2 Receptor in Trigeminal Ganglion Neurons of Mice.

Cyclooxygenase metabolizes dihomo-γ-linolenic acid and arachidonic acid to form prostaglandin (PG) E, including PGE1 and PGE2, respectively. Although PGE2 is well known to play an important role in the development and maintenance of hyperalgesia and allodynia, the role of PGE1 in pain is unknown. We confirm whether PGE1 induced pain using orofacial pain behavioral test in mice and determine the target molecule of PGE1 in TG neurons with whole-cell patch-clamp and immunohistochemistry. Intradermal injection of PGE1 to the whisker pads of mice induced a reduced threshold, enhancing the excitability of HCN channel-expressing trigeminal ganglion (TG) neurons. The HCN channel-generated inward current (Ih) was increased by 135.3 ± 4.8% at 100 nM of PGE1 in small- or medium-sized TG, and the action of PGE1 on Ih showed a concentration-dependent effect, with a median effective dose (ED50) of 29.3 nM. Adenylyl cyclase inhibitor (MDL12330A), 8-bromo-cAMP, and the EP2 receptor antagonist AH6809 inhibited PGE1-induced Ih. Additionally, PGE1-induced mechanical allodynia was blocked by CsCl and AH6809. PGE1 plays a role in mechanical allodynia through HCN2 channel facilitation via the EP2 receptor in nociceptive neurons, suggesting a potential therapeutic target in that PGE1 could be involved in pain as endogenous substances under inflammatory conditions.

The Long-term Effectiveness of the Automatic Position-Adaptive System in Spinal Cord Stimulation: A Retrospective Comparative Study with a Two-Year Follow-up.

OBJECTIVE: To 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. DESIGN: Retrospective study. SETTING: Tertiary university-based national hospital. SUBJECTS: Patients who underwent permanent SCS implantation procedures. METHODS: Patients 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. RESULTS: Of 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. CONCLUSIONS: There 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.

Commonalities and differences in abnormal peripheral metabolites between patients with fibromyalgia and complex regional pain syndrome.

Background: Fibromyalgia (FM) and complex regional pain syndrome (CRPS) share many pathological mechanisms related to chronic pain that could contribute to multifactorial pathological mechanisms.Methods: We investigated peripheral metabolites in FM and CRPS patients compared to healthy controls based on cross-sectional study.Results: Mean corpuscular hemoglobin (p < 0.001), mean corpuscular volume (p = 0.014), and total bilirubin levels (p = 0.017) were lower in FM patients than in healthy controls. On the other hand, CRPS patients showed lower levels of total bilirubin than healthy controls (p = 0.037). Creatinine level was lower in FM patients (p = 0.057) compared to healthy controls, particularly when comparing the low-hemoglobin subgroup among FM patients (p = 0.035) with the low-hemoglobin subgroup among healthy controls. Red blood cell count (r = -0.620, p = 0.031), hematocrit (r = -0.593, p = 0.042), and creatinine level (r = -0.598, p = 0.040) showed negative correlations with McGill Pain Questionnaire-Affective (MPQ-A) scores in FM patients. A negative correlation was observed between MCV and McGill Pain Questionnaire-Sensory scores (r = -0.680, p = 0.015) in CRPS patients.Conclusion: We found specific peripheral metabolites that may exhibit different tendency between FM and CRPS patients as well as some common metabolites, which may be associated with peripheral pathology in the patients. Considering this study had a few limitations such as a small sample sizes and using a liberal threshold of significance in the correlation analysis, future studies with larger sample sizes may be needed to generalize these findings.

Disruption of Homeostasis Based on the Right and Left Hemisphere in Patients with Complex Regional Pain Syndrome.

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.

Usefulness of the Korean Version of the CAGE-Adapted to Include Drugs Combined With Clinical Predictors to Screen for Opioid-Related Aberrant Behavior.

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.

Comparison of effectiveness of epidural analgesia and monitored anesthesia care for high-intensity focused ultrasound treatment of adenomyosis.

BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.