A prospective open label 2-8 year extension of the randomised controlled ICON trial on the long-term efficacy and safety of occipital nerve stimulation in medically intractable chronic cluster headache.

BACKGROUND: We demonstrated in the randomised controlled ICON study that 48-week treatment of medically intractable chronic cluster headache (MICCH) with occipital nerve stimulation (ONS) is safe and effective. In L-ICON we prospectively evaluate its long-term effectiveness and safety. METHODS: ICON participants were enrolled in L-ICON immediately after completing ICON. Therefore, earlier ICON participants could be followed longer than later ones. L-ICON inclusion was stopped after the last ICON participant was enrolled in L-ICON and followed for ≥2 years by completing six-monthly questionnaires on attack frequency, side effects, subjective improvement and whether they would recommend ONS to others. Primary outcome was the change in mean weekly attack frequency 2 years after completion of the ICON study compared to baseline. Missing values for log-transformed attack-frequency were imputed for up to 5 years of follow-up. Descriptive analyses are presented as (pooled) geometric or arithmetic means and 95% confidence intervals. FINDINGS: Of 103 eligible participants, 88 (85%) gave informed consent and 73 (83%) were followed for ≥2 year, 61 (69%) ≥ 3 year, 33 (38%) ≥ 5 years and 3 (3%) ≥ 8.5 years. Mean (±SD) follow-up was 4.2 ± 2.2 years for a total of 370 person years (84% of potentially 442 years). The pooled geometric mean (95% CI) weekly attack frequency remained considerably lower after one (4.2; 2.8-6.3), two (5.1; 3.5-7.6) and five years (4.1; 3.0-5.5) compared to baseline (16.2; 14.4-18.3). Of the 49/88 (56%) ICON ≥50% responders, 35/49 (71%) retained this response and 15/39 (38%) ICON non-responders still became a ≥50% responder for at least half the follow-up period. Most participants (69/88; 78% [0.68-0.86]) reported a subjective improvement from baseline at last follow-up and 70/88 (81% [0.70-0.87]) would recommend ONS to others. Hardware-related surgery was required in 44/88 (50%) participants in 112/122 (92%) events (0.35 person-year-1 [0.28-0.41]). We didn't find predictive factors for effectiveness. INTERPRETATION: ONS is a safe, well-tolerated and long-term effective treatment for MICCH. FUNDING: The Netherlands Organisation for Scientific Research, the Dutch Ministry of Health, the NutsOhra Foundation from the Dutch Health Insurance Companies, and Medtronic.

Evidence-based consensus guidelines on patient selection and trial stimulation for spinal cord stimulation therapy for chronic non-cancer pain.

Spinal cord stimulation (SCS) has demonstrated effectiveness for neuropathic pain. Unfortunately, some patients report inadequate long-term pain relief. Patient selection is emphasized for this therapy; however, the prognostic capabilities and deployment strategies of existing selection techniques, including an SCS trial, have been questioned. After approval by the Board of Directors of the American Society of Regional Anesthesia and Pain Medicine, a steering committee was formed to develop evidence-based guidelines for patient selection and the role of an SCS trial. Representatives of professional organizations with clinical expertize were invited to participate as committee members. A comprehensive literature review was carried out by the steering committee, and the results organized into narrative reports, which were circulated to all the committee members. Individual statements and recommendations within each of seven sections were formulated by the steering committee and circulated to members for voting. We used a modified Delphi method wherein drafts were circulated to each member in a blinded fashion for voting. Comments were incorporated in the subsequent revisions, which were recirculated for voting to achieve consensus. Seven sections with a total of 39 recommendations were approved with 100% consensus from all the members. Sections included definitions and terminology of SCS trial; benefits of SCS trial; screening for psychosocial characteristics; patient perceptions on SCS therapy and the use of trial; other patient predictors of SCS therapy; conduct of SCS trials; and evaluation of SCS trials including minimum criteria for success. Recommendations included that SCS trial should be performed before a definitive SCS implant except in anginal pain (grade B). All patients must be screened with an objective validated instrument for psychosocial factors, and this must include depression (grade B). Despite some limitations, a trial helps patient selection and provides patients with an opportunity to experience the therapy. These recommendations are expected to guide practicing physicians and other stakeholders and should not be mistaken as practice standards. Physicians should continue to make their best judgment based on individual patient considerations and preferences.

Development and validation of a multivariable prediction model for early prediction of chronic postsurgical pain in adults: a prospective cohort study.

BACKGROUND: Early identification of patients at risk of developing chronic postsurgical pain (CPSP) is an essential step in reducing pain chronification in postsurgical patients. We aimed to develop and validate a prognostic model for the early prediction of CPSP including pain characteristics indicating altered pain processing within 2 weeks after surgery. METHODS: A prospective cohort study was conducted in adult patients undergoing orthopaedic, vascular, trauma, or general surgery between 2018 and 2019. Multivariable logistic regression models for CPSP were developed using data from the University Medical Centre (UMC) Utrecht and validated in data from the Erasmus UMC Rotterdam, The Netherlands. RESULTS: In the development (n=344) and the validation (n=150) cohorts, 28.8% and 21.3% of patients reported CPSP. The best performing model (area under the curve=0.82; 95% confidence interval [CI], 0.76-0.87) included preoperative treatment with opioids (odds ratio [OR]=4.04; 95% CI, 2.13-7.70), bone surgery (OR=2.01; 95% CI, 1.10-3.67), numerical rating scale pain score on postoperative day 14 (OR=1.57; 95% CI, 1.34-1.83), and the presence of painful cold within the painful area 2 weeks after surgery (OR=4.85; 95% CI, 1.85-12.68). Predictive performance was confirmed by external validation. CONCLUSIONS: As only four easily obtainable predictors are necessary for reliable CPSP prediction, the models are useful for the clinician to be alerted to further assess and treat individual patients at risk. Identification of the presence of painful cold within 2 weeks after surgery as a strong predictor supports altered pain processing as an important contributor to CPSP development.

[Is bone marrow edema a cause of low back pain? A possible role of bacteria]. / Is eindplaatoedeem van wervellichamen een oorzaak van lage-rugpijn?

Lumbar bone marrow edema, also known as Modic type-1 endplate change, has a prevalence of 43% in low back pain populations and 6% in general populations. Besides mechanical factors and genetic predisposition it has been hypothesized that lumbar bone marrow edema is caused by a latent infection of low-virulence anaerobic bacteria in degenerated lumbar intervertebral discs. The hypothesis is supported by the observation that the presence of Cutibacterium acnes is more frequently found in samples of disci with Modic-1 than in discs without and by the positive effects of antibiotics in patients with back pain and Modic-1 as shown in placebo-controlled RCT's. Opponents of the hypothesis argue that the findings of bacteria are most likely a result of contamination during harvesting the samples. We conclude that time has come to make a start in the Netherlands with treatment with antibiotics of a small group of well-selected patients in well-selected clinics.

Postoperative Pain and Age: A Retrospective Cohort Association Study.

BACKGROUND: As the population ages, the number of elderly people undergoing surgery increases. Literature on the incidence and intensity of postoperative pain in the elderly is conflicting. This study examines associations between age and pain-related patient reported outcomes and perioperative pain management in a dataset of surgical patients undergoing four common surgeries: spinal surgery, hip or knee replacement, or laparoscopic cholecystectomy. Based on the authors' clinical experience, they hypothesize that pain scores are lower in older patients. METHODS: In this retrospective cohort, study data were collected between 2010 and 2018 as part of the international PAIN OUT program. Patients filled out the International Pain Outcomes Questionnaire on postoperative day 1. RESULTS: A total of 11,510 patients from 26 countries, 59% female, with a mean age of 62 yr, underwent one of the aforementioned types of surgery. Large variation was detected within each age group for worst pain, yet for each surgical procedure, mean scores decreased significantly with age (mean Numeric Rating Scale range, 6.3 to 7.3; ß = -0.2 per decade; P ≤ 0.001), representing a decrease of 1.3 Numeric Rating Scale points across a lifespan. The interference of pain with activities in bed, sleep, breathing deeply or coughing, nausea, drowsiness, anxiety, helplessness, opioid administration on the ward, and wish for more pain treatment also decreases with age for two or more of the procedures. Across the procedures, patients reported being in severe pain on postoperative day one 26 to 38% of the time, and pain interfered moderately to severely with movement. CONCLUSIONS: The authors' findings indicate that postoperative pain decreases with increasing age. The change is, however, small and of questionable clinical significance. Additionally, there are still too many patients, at any age, undergoing common surgeries who suffer from moderate to severe pain, which interferes with function, supporting the need for tailoring care to the individual patient.

Isotopic Scintigraphy in Intrathecal Drug Delivery Failure: A Single-Institution Case Series.

BACKGROUND: The aim of this study was to assess the feasibility and diagnostic accuracy of an optimized 111 Indium-diethylenetriamine-penta-acetic-acid single-photon-emission computed tomography (CT) (111 In-DTPA SPECT-CT) examination in patients with suspected intrathecal drug delivery (ITDD) failure. MATERIALS AND METHODS: Retrospective analysis of routinely collected observational data from a case series of patients in the setting of the academic Center for Pain Medicine, Departments of Radiology and Nuclear Medicine and Neurosurgery. Twenty-seven patients participated between January 2014 and January 2019. Thirty-six optimized examinations including standardized pump flow rate with additional SPECT-CT imaging and a stepwise standardized analysis were performed. A 10 mL mixture of medication and 20 MBq 111In-DTPA was injected into the pump reservoir. Planar and SPECT-CT images were acquired at 24, 48, and 72 hours (h) after injection and at 96 hours and/or seven days, if needed. All images were reassessed by the first two authors using an optimized procedure. RESULTS AND CONCLUSIONS: Twenty-two abnormalities were identified in 21 examinations, with these abnormalities consisting of leakage (n = 7), spinal catheter obstruction (n = 7), and cerebrospinal fluid flow obstruction (n = 8). Interventions (n = 19) confirmed the cause of ITDD failure. A false-positive finding at follow-up (n = 1) and a false-negative finding (n = 1) were encountered. Sensitivity was 95% (20/21) and the specificity 93% (14/15). A significant difference (p < 0.001) was found between the accuracy of the conventical and the optimized analysis. The optimized 111 In-DTPA SPECT-CT examination is a powerful diagnostic tool for detecting the cause of ITDD failure.

Effectiveness of Epiduroscopy for Patients with Failed Back Surgery Syndrome: A Systematic Review and Meta-analysis.

INTRODUCTION: Low-back or leg pain in patients suffering from failed back surgery syndrome (FBSS) is often severe, having a major impact on functionality and quality of life. Despite conservative and surgical treatments, pain can be persistent. An alternative treatment option is epiduroscopy, a minimally invasive procedure based on mechanical adhesiolysis of epidural fibrosis. As epidural fibrosis is speculated to be a major contributor in the pathophysiologic process of FBSS, this review evaluates the effectiveness of epiduroscopy in FBSS patients. METHODS AND MATERIALS: A systematic literature search was performed in PubMed, Embase, and Cochrane databases. Critical appraisal was performed using validated tools. Meta-analysis was performed using generic inverse variance analysis. RESULTS: From the 286 identified articles, nine studies were included. The visual analogue scale (VAS) average was 7.6 at baseline, 4.5 at 6, and 4.3 at 12 months. The Oswestry Disability Index (ODI) average was 61.7% at baseline, 42.8% at 6, and 46.9% at 12 months. An average of 49% of patients experienced significant pain relief at 6 and 37% at 12 months. Meta-analysis showed a pooled VAS mean difference of 3.4 (2.6 to 4.1; 95% confidence interval [CI]) and 2.8 (1.6 to 4.0; 95% CI) and pooled ODI mean difference of 19.4% (12.5 to 26.4%; 95% CI) and 19.8% (13.8 to 25.9%; 95% CI) at 6 and 12 months, respectively. CONCLUSION: Current literature demonstrates a clinically relevant reduction in pain and disability scores at 6 to 12 months after mechanical adhesiolysis in FBSS patients. The quality of evidence is moderate, and the level of recommendation is weak. Practitioners should consider the benefits of epiduroscopy after weighing the risks for individual patients with FBSS.

Cost-effectiveness of combination therapy (Mechanical Diagnosis and Treatment and Transforaminal Epidural Steroid Injections) among patients with an indication for a Lumbar Herniated Disc surgery: Protocol of a randomized controlled trial.

OBJECTIVES: The general consensus is that surgical treatment is advised when conservative methods fail in patients with lumbosacral radicular syndrome (LRS). Preliminary evidence from our pilot study indicates that combination therapy (mechanical diagnosis therapy and transforaminal epidural injections) can prevent surgical treatment in patients on the waiting list for surgery. The pilot study lacked a control group, and therefore, firm conclusions pertaining to effects could not be made. This study aims to determine if combination therapy, performed while being on the waiting list for lumbar herniated disc surgery, is effective and cost-effective compared with usual care (i.e., no intervention while being on the waiting list) among patients with a magnetic resonance imaging (MRI)-confirmed indication for a lumbar herniated disc surgery. METHODS: A randomized controlled trial will be conducted with an economic evaluation. Patients aged 18 and above with incapacitating LRS, with leg pain and an MRI confirmed indication for lumbar disc hernia surgery, will be recruited from seven Dutch hospitals. While being on the waiting list for lumbar herniated disc surgery, patients will be randomized to either the combination therapy or usual care group. The primary outcome measure is the number of patients undergoing lumbar disc surgery during 12-month follow-up. Secondary outcomes include back and leg pain intensity (numeric pain rating scale), physical functioning (Roland Morris Disability Questionnaires-23), self-perceived recovery (global perceived effect), and health-related quality of life (EuroQol Five Dimensions Health Questionnaire (EQ-5D-5L) and 12-Item Short Form Health Survey (SF-12)). For the economic evaluation, societal and health care costs will be measured. Measurements moments are baseline, 1, 2, 4, 6, 9, and 12 months. Data will be analysed according to the intention-to-treat principle. CONCLUSION: No randomized controlled trials have evaluated the effectiveness and cost-effectiveness of combination therapy compared with usual care in patients with an indication for lumbar herniated disc surgery, which emphasizes the importance of this study.

Effectiveness and Safety of Dorsal Root Ganglion Stimulation for the Treatment of Chronic Pain: A Pooled Analysis.

INTRODUCTION: Since it became available in the mid-2010s, dorsal root ganglion (DRG) stimulation has become part of the armamentarium to treat chronic pain. To date, one randomized controlled trial, and several studies of moderate sample size and various etiologies have been published on this topic. We conducted a pooled analysis to investigate the generalizability of individual studies and to identify differences in outcome between chronic pain etiologic subgroups and/or pain location. MATERIALS AND METHODS: One prospective, randomized comparative trial and six prospective, single-arm, observational studies were identified that met pre-defined acceptance criteria. Pain scores and patient-reported outcome (PRO) measures were weighted by study sample sizes and pooled. Safety data are reported in aggregate form. RESULTS: Our analysis included 217 patients with a permanent implant at 12-month follow-up. Analysis of pooled data showed an overall weighted mean pain score of 3.4, with 63% of patients reporting ≥50% pain relief. Effectiveness sub-analyses in CRPS-I, causalgia, and back pain resulted in a mean reduction in pain intensity of 4.9, 4.6, and 3.9 points, respectively. Our pooled analysis showed a pain score for primary affected region ranging from 1.7 (groin) to 3.0 (buttocks) and responder rates of 80% for foot and groin, 75% for leg, and 70% for back. A substantial improvement in all PROs was observed at 12 months. The most commonly reported procedural or device complications were pain at the IPG pocket site, lead fracture, lead migration, and infection. CONCLUSIONS: DRG stimulation is an effective and safe therapy for various etiologies of chronic pain.

Evaluating Dorsal Root Ganglion Stimulation in a Prospective Dutch Cohort.

OBJECTIVES: Dorsal root ganglion (DRG) stimulation is a recent neuromodulation option that has delivered safe, effective pain relief for a number of etiologies. This prospective observational study was intended to establish the effectiveness of this treatment in a typical real-world clinical context. MATERIALS AND METHODS: Participants with chronic, intractable pain of the trunk or lower limbs were recruited from multiple pain clinics in the Netherlands. Subjects were trialed and implanted with DRG stimulation systems. Pain, function, mood, and quality of life, ratings were collected through 12 months postimplant. RESULTS: Of the 66 subjects enrolled, failed back surgery syndrome, peripheral nerve injury, and complex regional pain syndrome formed the largest etiologies. Permanent implants were placed in 86.2% subjects (56/65). After 12 months of treatment, average pain ratings in subjects' primary area of pain decreased from 8.0 cm at baseline to 4.1 cm, and 49% of subjects had ≥50% reduction in pain (visual analog scale). In addition, functional capacity was increased, and mood and quality of life improved. No confirmed lead migrations were observed, and there was a low rate of infection. CONCLUSIONS: DRG stimulation significantly reduced the severity of subjects' pain and enabled participatory changes that improved quality of life through 12-months postimplant.

Lower sex hormone levels are associated with more chronic musculoskeletal pain in community-dwelling elderly women.

Chronic pain is more prevalent in women than in men, with increasing differences between sexes in advanced age. This could be caused by differences in sex hormone levels. We therefore studied the relationship between sex hormones and the prevalence and incidence of chronic pain. The association between sex hormone levels and chronic pain was examined in 9717 participants aged 45 years and older from the Rotterdam Study, a population-based study. Chronic pain was defined as pain in the lower back, hands, knees and/or hips for at least 3 months. Sex hormone levels included estrogen, testosterone, androstenedione, and 17-hydroxyprogesterone. Relationships between hormones and prevalent and new onset chronic pain were analyzed using linear and logistic regression, stratified by gender. Women with androstenedione or estradiol levels in the lowest tertile had more chronic pain (odds ratio, 1.20; 95% CI, 1.03-1.39 and odds ratio, 1.27; 95% CI, 1.10-1.48, respectively). Mean estradiol levels were lower among men with chronic pain (mean difference -3.88 pmol/L; P = 0.005). Lowest tertile 17-hydroxyprogesterone in women was associated with 38% more new onset pain. All these associations were independent from age, body mass index, health and lifestyle factors, and osteoarthritis. Lower sex hormone levels are associated with chronic musculoskeletal pain, independent from lifestyle and health-related factors, in community-dwelling elderly women. These results suggest that sex hormones play a role in chronic pain and should be taken into account when a patient presents with chronic pain. Therefore, sex hormones may be a potential treatment target for these patients.

One-year outcomes of spinal cord stimulation of the dorsal root ganglion in the treatment of chronic neuropathic pain.

OBJECTIVES: Spinal cord stimulation of the dorsal root ganglion (DRG-SCS) is a new therapy for treating chronic neuropathic pain. Previous work has demonstrated the effectiveness of DRG-SCS for pain associated with failed back surgery syndrome, complex regional pain syndrome, chronic postsurgical pain, and other etiologies through 6 months of treatment; this report describes the maintenance of pain relief, improvement in mood, and quality of life through 12 months. MATERIALS AND METHODS: Subjects with intractable pain in the back and/or lower limbs were implanted with an active neurostimulator device. Up to four percutaneous leads were placed epidurally near DRGs. Subjects were tracked prospectively for 12 months. RESULTS: Overall, pain was reduced by 56% at 12 months post-implantation, and 60% of subjects reported greater than 50% improvement in their pain. Pain localized to the back, legs, and feet was reduced by 42%, 62%, and 80%, respectively. Measures of quality of life and mood were also improved over the course of the study, and subjects reported high levels of satisfaction. Importantly, excellent pain-paresthesia overlap was reported, remaining stable through 12 months. DISCUSSION: Despite methodological differences in the literature, DRG-SCS appears to be comparable to traditional SCS in terms of pain relief and associated benefits in mood and quality of life. Its benefits may include the ability to achieve precise pain-paresthesia concordance, including in regions that are typically difficult to target with SCS, and to consistently maintain that coverage over time.

[Multidisciplinary practice guideline 'Invasive treatment of spine related low back pain']. / Multidisciplinaire richtlijn 'Wervelkolomgerelateerde pijnklachten van de lage rug'.

The practice guideline 'Invasive treatment of spine related low back pain' describes the state of the art regarding the diagnosis and value of invasive treatment after failure of conservative treatment in patients with pain symptoms of facet joint pain, pain in the sacroiliac joint, coccygodynia, discogenic pain and the 'failed back surgery syndrome'. There is no consensus on definitions and a classification system for chronic low back pain symptoms. The classification in specific and nonspecific low back pain provides insufficient insight and is unable to show which therapy is effective for which disorder. The guideline working group advises a new classification system for chronic low back pain in degenerative and non-degenerative disorders. After failure of conservative treatment, several specific invasive treatments are recommended; some of these treatments should only be performed in study related settings. Some of the treatments that are currently used in daily practice are inadvisable.

Report of a preliminary discontinued double-blind, randomized, placebo-controlled trial of the anti-TNF-α chimeric monoclonal antibody infliximab in complex regional pain syndrome.

OBJECTIVE: Inflammation appears to play a role in CRPS as, for example, cytokines (like TNF-α) are involved in the affected limb. The ongoing inflammation is probably responsible for the central sensitization that sometimes occurs in CRPS. Thus, early start of a TNF-α antagonist may counteract inflammation, thereby preventing rest damage and leading to recovery of the disease. DESIGN: Patients (n = 13) were randomly assigned to infliximab 5 mg/kg or placebo, both administered at week 0, 2, and 6. OUTCOME MEASURES: The aim was to confirm a reduction in clinical signs of regional inflammation (based on total impairment level sumscore: ISS) after systemic administration of infliximab. Also, levels of mediators in the fluid of induced blisters were examined in relation to normalization and improvement in quality of life. RESULTS: Six patients received infliximab and 7, placebo. There was no significant change in total ISS score between the two groups. Similarly, no significant difference in change in cytokine levels was found between infliximab compared with placebo. However, there was a trend toward a greater reduction of TNF-α in the intervention group compared with the placebo group. A subscale of the EuroQol (ie EuroQol VAS) revealed significant decrease in health status in the intervention group compared with the placebo group. CONCLUSIONS: This study was terminated before the required number of participants had been reached for sufficient statistical power. Nevertheless, a trend was found toward an effect of infliximab on the initially high TNF-α concentration.

Effect of immunomodulating medications in complex regional pain syndrome: a systematic review.

BACKGROUND: Different mechanisms are involved in a complex network of interactions resulting in the painful and impairing disorder, complex regional pain syndrome (CRPS). There is convincing evidence that inflammation plays a pivotal role in the pathophysiology of CRPS. Immunomodulating medication reduces the manifestation of inflammation by acting on the mediators of inflammation. Therefore, as inflammation is involved in the pathophysiology of CRPS, immunomodulating medication in CRPS patients may prove beneficial. OBJECTIVES: To describe the current empirical evidence for the efficacy of administering the most commonly used immunomodulating medication (ie, glucocorticoids, tumor necrosis factor-α antagonists, thalidomide, bisphosphonates, and immunoglobulins) in CRPS patients. METHODS: PubMed was searched for original articles that investigated CRPS and the use of one of the abovementioned immunomodulating agents. RESULTS: The search yielded 39 relevant articles: from these, information on study design, sample size, duration of disease, type and route of medication, primary outcome measures, and results was examined. DISCUSSION: Theoretically, the use of immunomodulating medication could counteract the ongoing inflammation and might be an important step in improving a disabled hand or foot, leading to further recovery. However, more high-quality intervention studies are needed.

Cost-effectiveness of minimal interventional procedures for chronic mechanical low back pain: design of four randomised controlled trials with an economic evaluation.

BACKGROUND: Minimal interventional procedures are frequently applied in patients with mechanical low back pain which is defined as pain presumably resulting from single sources: facet, disc, sacroiliac joint or a combination of these. Usually, these minimal interventional procedures are an integral part of a multidisciplinary pain programme. A recent systematic review issued by the Dutch Health Insurance Council showed that the effectiveness of these procedures for the total group of patients with chronic low back pain is yet unclear and cost-effectiveness unknown. The aim of the study is to evaluate whether a multidisciplinary pain programme with minimal interventional procedures is cost-effective compared to the multidisciplinary pain programme alone for patients with chronic mechanical low back pain who did not respond to conservative primary care and were referred to a pain clinic. METHODS: All patients with chronic low back pain who are referred to one of the 13 participating pain clinics will be asked to participate in an observational study. Patients with a suspected diagnosis of facet, disc or sacroiliac joint problems will receive a diagnostic block to confirm this diagnosis. If confirmed, they will be asked to participate in a randomized controlled trial (RCT). For each single source a separate RCT will be conducted. Patients with a combination of facet, disc or sacroiliac joint problems will be invited for participation in a RCT as well. An economic evaluation from a societal perspective will be performed alongside these four RCTs. Patients will complete questionnaires at baseline, 3 and 6 weeks, 3, 6, 9 and 12 months after start of the treatment. Costs will be collected using self-completed cost questionnaires. DISCUSSION: No trials are yet available which have evaluated the cost-effectiveness of minimal interventional procedures in patients with chronic mechanical low back pain, which emphasizes the importance of this study. TRIAL REGISTRATION NUMBER: National Trial Register: NTR3531.

Rewarming patterns in hand fracture patients with and without cold intolerance.

PURPOSE: It is often assumed that cold intolerance is associated with abnormalities in the skin temperature due to changes in the blood flow of the hands. In this study, we determined whether patients with and without cold intolerance after a hand fracture or healthy controls have a diminished rewarming after a cold stimulus. METHODS: The severity of cold intolerance was evaluated using the Cold Intolerance Symptom Severity (CISS) questionnaire. To determine whether abnormal rewarming plays a major role in the underlying pathophysiology of cold intolerance, a cold-stress test was applied at a mean of 30 months (with a range of 11 mo) after the patients recovered from a hand fracture. A control group also underwent identical cold-stress testing for comparison. Temperature during the rewarming phase was measured using videothermography. RESULTS: Thirteen control subjects and 18 patients participated. Control subjects did not report any symptoms of cold intolerance (CISS score, 0) and no loss of sensibility was measured. The mean CISS score of all patients was 27.8; 9 patients scored above the cut-off value for normal cold intolerance. No significant differences were found in the rewarming patterns between (1) the affected and non-affected hand of the postfracture patients, (2) the dominant and non-dominant hand of the control subjects, and (3) the patients and controls. CONCLUSIONS: The results of this study revealed no relation between the severity of cold intolerance and rewarming patterns after cold stress testing. This might suggest that temperature regulation of the hands in post-fracture patients might not be responsible for the symptoms of cold intolerance, based on cold-stress test response.

Is there an association between psychological factors and the Complex Regional Pain Syndrome type 1 (CRPS1) in adults? A systematic review.

Complex Regional Pain Syndrome type 1 (CRPS1) is a complication after trauma or surgery. Its pathophysiology is still a matter of debate, and psychological factors have been suggested to play a role, although their influence is unclear. The aim of this study was to investigate the evidence for the influence of psychological factors on the onset and maintenance of CRPS1 in adults. In a systematic review, articles were selected using Cochrane, Pubmed/Medline, Psychinfo, and Cinahl since 1980. Only original articles and empirical studies were included. Based on these selection criteria, 31 articles were identified. Studies were evaluated and weighted using a quality assessment instrument. The few prospective studies do not report a relationship between CRPS1 and depression, anxiety, neuroticism, or anger. The results of the retrospective/cross-sectional studies yield contradictory results regarding psychological problems in patients with CRPS1. A majority show no association, and studies with a higher methodological quality lean to a conclusion of no relationship between psychological factors and CRPS1. The majority of included studies (N=24; 77%) had only a poor to moderate methodological quality. Although many patients with CRPS1 are stigmatized as being psychologically different, this literature review identified no relationship between CRPS1 and several psychological factors. Only life events seemed to be associated with CRPS1: patients who experienced more life events appeared to have a greater chance of developing CRPS1. More studies with greater methodological quality and more participants should be performed on the association between psychological factors and the development and course of CRPS1.

Six years follow-up of the levels of TNF-alpha and IL-6 in patients with complex regional pain syndrome type 1.

In an earlier study, levels of the proinflammatory cytokines TNF-alpha and IL-6 are higher in blisters fluid from the complex regional pain syndrome type 1 (CRPS1) side obtained at 6 and 30 months (median) after the initial event. The aim of this follow-up study is to determine the involvement of these cytokines in long lasting CRPS1. Twelve CRPS1 patients, with median disease duration of 72 months, participated. The levels of TNF-alpha and IL-6 were measured in blister fluid; disease activity was reevaluated by measuring pain and differences in temperature, volume, and mobility between both extremities. Differences in levels of IL-6 and TNF-alpha and mobility between both sides were significantly decreased. Pain and differences in temperature and volume were not significantly altered. No correlation was found between the cytokines and the disease characteristics. These results indicate that IL-6 and TNF-alpha are only partially responsible for the signs and symptoms of CRPS1.