Stem cells: Targeting pain of spinal-cord injury
Nature 537, 7622 (2016). doi:10.1038/537588d
Neurons derived from human embryonic stem cells can reduce pain and other effects of spinal-cord injury in mice.Persistent nerve pain and loss of bladder control often follow spinal-cord injury, and may be linked to reduced signalling by the inhibitory neurotransmitter GABA. Thomas Fandel and
Abstract: Complex regional pain syndrome type I (CRPS-I) highly affects patients' ability to perform daily life activities. Pain-related fear might be a key target to reduce disability in chronic pain. Current treatments aiming at reducing pain show little improvements on pain and disability, whereas novel exposure-based treatments targeting pain-related fears have shown to be promising. We conducted a randomized controlled trial (N = 46) comparing exposure in vivo (EXP) with pain-contingent treatment as usual (TAU), for CRPS-I patients with at least moderate levels of pain-related fear. Primary outcome is self-reported disability, for upper and lower extremity, respectively. Secondary outcomes are self-reported pain-intensity, pain-catastrophizing, perceived harmfulness of physical activity, and health-related quality of life. Pretreatment to posttreatment and pretreatment to 6-month follow-up change scores were tested using randomization-based inference. EXP was superior to TAU in reducing upper extremity disability from pretreatment to posttreatment (between-group difference, 1.082; 95% confidence interval [CI], 0.563-1.601; P < 0.001) and from pretreatment to 6-month follow-up (1.303; 95% CI, 0.917-1.690; P < 0.001). EXP was superior in reducing lower extremity disability from pretreatment to 6-month follow-up (3.624; 95% CI, 0.467-6.781; P = 0.02), but not from pretreatment to posttreatment (3.055; 95% CI, −0.018 to 6.128; P = 0.054). All secondary outcomes significantly favored EXP pretreatment to posttreatment, as well as pretreatment to 6-month follow-up. Exposure to daily activities shows to be more effective than a protective pain-contingent TAU in reducing self-reported disability in daily life of CRPS-I patients with at least moderate levels of pain-related fear.
Abstract: Burrowing, an ethologically relevant rodent behaviour, has been proposed as a novel outcome measure to assess the global impact of pain in rats. In a prospective multicentre study using male rats (Wistar, Sprague-Dawley), replication of suppressed burrowing behaviour in the complete Freund adjuvant (CFA)-induced model of inflammatory pain (unilateral, 1 mg/mL in 100 µL) was evaluated in 11 studies across 8 centres. Following a standard protocol, data from participating centres were collected centrally and analysed with a restricted maximum likelihood-based mixed model for repeated measures. The total population (TP—all animals allocated to treatment; n = 249) and a selected population (SP—TP animals burrowing over 500 g at baseline; n = 200) were analysed separately, assessing the effect of excluding “poor” burrowers. Mean baseline burrowing across studies was 1113 g (95% confidence interval: 1041-1185 g) for TP and 1329 g (1271-1387 g) for SP. Burrowing was significantly suppressed in the majority of studies 24 hours (7 studies/population) and 48 hours (7 TP, 6 SP) after CFA injections. Across all centres, significantly suppressed burrowing peaked 24 hours after CFA injections, with a burrowing deficit of −374 g (−479 to −269 g) for TP and −498 g (−609 to −386 g) for SP. This unique multicentre approach first provided high-quality evidence evaluating suppressed burrowing as robust and reproducible, supporting its use as tool to infer the global effect of pain on rodents. Second, our approach provided important informative value for the use of multicentre studies in the future.Although specific psychological disorders in complex regional pain syndrome (CRPS) have not been identified, studies suggest that CRPS patients may have increased rates of traumatic life events. Because these events do not always lead to apparent psychological symptoms, we systematically screened CRPS patients for posttraumatic stress disorder (PTSD) to determine if PTSD could be a risk factor for CRPS.
Consecutive CRPS patients referred to two university hospital centres (University of Erlangen, UMC Mainz) between December 2011 and April 2013 were prospectively examined using a diagnostic PTSD instrument (Post-traumatic Stress Diagnostic Scale (PDS). We also tested maladaptive coping strategies (brief-COPE inventory) and the PDS severity score as predictors for CRPS. Patients with non-CRPS extremity pain and healthy individuals were used as control groups.
We collected data from 152 patients with CRPS, 55 control patients and 55 age- and sex-matched healthy individuals. Fifty-eight CRPS patients (38%), six non-CRPS pain patients (10%) and two healthy individuals (4%) met diagnostic criteria for PTSD. Initial PTSD symptom onset was prior to CRPS in 50 CRPS patients (86%) and during the course of CRPS in eight patients. Results of a logistic regression revealed that the PTSD severity score was associated with CRPS (p < 0.0001). Maladaptive coping strategies (p < 0.0001) were related to PTSD.
posttraumatic stress disorder (PTSD) is more frequent in patients with CRPS than it is in the general population.
Research has not yet provided support for specific psychological predictors for CRPS.
Serotonin–norepinephrine reuptake inhibitors inhibit the reuptake of serotonin and noradrenalin and are used in the treatment of neuropathic pain. Animal studies suggest that milnacipran co-administered with opioids may potentiate the analgesic effect of μ-opioid receptor agonists. This study hypothesized that co-administration of milnacipran and buprenorphine would have a synergistic effect in evoked pain models in healthy subjects.
This was a randomized double-blinded, placebo-controlled, four-way cross-over, multiple dose clinical trial to investigate the analgesic effects of buprenorphine (placebo, 0.5, 1 and 3 μg/kg) in combination with milnacipran (placebo, 25 and 50 mg) in healthy subjects.
11 healthy men were enrolled in the study. Buprenorphine alone showed a dose–response relationship indicative of anti-nociception in the pain tests. Following milnacipran administration, no changes were seen in the pharmacodynamic measurements for pain, psychomotor function, body stability or eye movements. For the electrical tests, cold pressor test and pressure pain test, buprenorphine alone was superior when compared with buprenorphine plus milnacipran. No differences in pharmacodynamic variables, besides an increase in pupil/iris ratio, were observed after repeated administration of milnacipran 50 mg. Single and multiple doses of 25 or 50 mg milnacipran did not further potentiate the anti-nociceptive effects of buprenorphine.
Buprenorphine showed dose-dependent effects consistent with its pharmacological profile. Milnacipran alone did not affect any of the pain variables. The combination of both buprenorphine and milnacipran did not potentiate or show a synergistic effect on the pain models used in this study.
Buprenorphine is known to be a potent opioid agonist. Animal studies suggest that milnacipran co-administered with opioids may potentiate the analgesic effect of μ-opioid receptor agonists. Here, we found that buprenorphine showed a dose-dependent analgesic effect, but that no potentiation or synergy on a battery of evoked pain tasks could be observed after co-administration of both milnacipran and buprenorphine.
Tissue pH is lowered in inflamed tissues, and the increased proton concentration activates acid-sensing ion channels (ASICs), contributing to pain and hyperalgesia. ASICs can be upregulated by nerve growth factor (NGF). The aim of this study was to investigate two new human experimental pain models combining NGF- and acid-induced pain in a randomized, controlled, double-blind study.
In experiment 1, volunteers (N = 16) received an injection of either NGF or isotonic saline in each infrapatellar fat pad (IFP). One day after 5 mL of phosphate-buffered acidic saline was infused into each IFP at a rate of 20 mL/h. In experiment 2, the tibialis anterior (TA) muscle of additional volunteers (N = 16) was examined, following the same procedure except that the volume and infusion rate of acid were different (10 mL, 30 mL/h). Continuous pain ratings were recorded during and after acid infusions. In addition, soreness scores on a Likert scale and pressure pain thresholds (PPTs) were assessed.
The PPT of the IFP was significantly decreased at the NGF injection site on day 1, but acid-provoked pain ratings and the change in PPT from pre- to postinfusion between the knees were similar. In the muscle pain model, local mechanical hyperalgesia developed 3 h after the NGF injection and a significant additional decrease in PPT was found after acid infusion compared to preinfusion.
NGF sensitization in the IFP was not facilitated by acid, whereas an acid-provoked enhancement of muscle hyperalgesia was found. NGF sensitization of adipose tissue responds differently to acid provocation compared to muscle tissue.
Quantification of two novel pain models combining NGF and acid. Hyperalgesia developed after NGF injection in the infrapatellar fat pad, but it was not facilitated by acid provocation. Contrary, NGF-induced hyperalgesia in muscle tissue was enhanced by acid.
Patients with fibromyalgia (FM) exhibit significant clinical heterogeneity, in terms of physical, social and psychological functions, as well as therapeutic responses. Here, we examined FM patients in terms of pain, physical, social and psychological variables to identify clinical subgroups that may be predictive of treatment patterns.
A total of 313 FM patients were interviewed using a structured questionnaire that included sociodemographic data, current or past FM symptoms and current use of relevant medications. A K-means cluster analysis was conducted using variables reflecting tender points, the Fibromyalgia Impact Questionnaire, Beck Depression Inventory, State-Trait Anxiety Inventor and Social Support Scale.
Four distinct clusters were identified in these patients. Group 1 was characterized by high pain levels, severe physical and mental impairment and low social support. Group 2 had moderate pain and physical impairment, mild mental impairment and moderate social support. Group 3 had moderate pain, low physical and moderate mental impairment and low social support. Group 4 had low pain levels, nearly normal physical and mental function and high social support. Group 1 was more often a current or past smoker, more likely to have a variety of symptoms, including swelling, cognitive dysfunction, dizziness, syncope, oesophageal dysmotility, dyspepsia, irritable bladder, vulvodynia and restless leg syndrome.
We identified four subgroups of FM patients based on pain, physical, social and psychological function. These subgroups had different clinical symptoms and medication profiles, suggesting that FM may be better managed using a more comprehensive assessment of an individual patient's symptoms.
FM patients can be clustered into four distinct subgroups based on clinically measurable variables – pain, physical involvement, psychological function and social support. These subgroups had different clinical symptoms and medication profiles.
No core set of measurement tools exists to collect data within clinical practice. Such data could be useful as reference data to guide treatment decisions and to compare patient characteristics or treatment results within specific treatment settings.
The Dutch Dataset Pain Rehabilitation was developed which included the six domains of the IMMPACT core set and three new domains relevant in the field of rehabilitation (medical consumption, patient-specific goals and activities/participation). Between 2010 and 2013 the core set was implemented in 32 rehabilitation facilities throughout the Netherlands.
A total of 8200 adult patients with chronic pain completed the core set at first consultation with the rehabilitation physician. Adult patients (18–90 years) suffering from a long history of pain (38% >5 years) were referred. Patients had high medical consumption and less than half were working. Although patients were referred with diagnosis of low back pain or neck or shoulder pain, a large group (85%) had multisite pain (39% 2–5 painful body regions; 46% >5 painful body regions). Scores on psychosocial questionnaires were high, indicating high case complexity of referred patients. Reference data for subgroups based on gender, pain severity, pain locations and on pain duration are presented.
The data from this clinical core set can be used to compare patient characteristics of patients of other treatment setting and/or scientific publications. As treatment success might depend on case complexity, which is high in the referred patients, the advantages of earlier referral to comprehensive multidisciplinary treatment were discussed.
A detailed description of case complexity of patients with chronic pain referred for pain rehabilitation. Insight in case complexity of patients within subgroups on the basis of gender, pain duration, pain severity and pain location. These descriptions can be used as reference data for daily practice in the field of pain rehabilitation and can be used to evaluate, monitor and improve rehabilitation care in care settings nationwide as well as internationally.
Epidemiological studies on chronic pelvic pain (CPP) have focused on women of reproductive age. We aimed to determine the prevalence of chronic pelvic pain (CPP) in adult women and the differences in associated factors among women of reproductive age and older women. In addition, to determine whether distinct subgroups existed among CPP cases.
A cross-sectional postal survey was conducted among 5300 randomly selected women aged ≥25 years resident in the Grampian region, UK. Multivariable logistic regression was used to determine pregnancy-related and psychosocial factors associated with CPP. To identify subgroups of CPP cases, we performed cluster analysis using variables of pain severity, psychosocial factors and pain coping strategies.
Of 2088 participants, 309 (14.8%) reported CPP. CPP was significantly associated with being of reproductive age (odds ratios (OR) 2.43, 95% CI 1.69–3.48), multiple non-pain somatic symptoms (OR 3.58 95% CI 2.23–5.75), having fatigue (OR mild 1.74 95% CI 1.24–2.44, moderate/severe 1.82, 95% CI 1.25–2.63) and having depression (OR 1.61, 95% CI 1.09–2.38). CPP was less associated with multiple non-pain somatic symptoms in women of reproductive age compared to older women (interaction OR 0.51, 95% CI 0.28–0.92). We identified two clusters of CPP cases; those having little/no psychosocial distress and those having high psychosocial distress.
CPP is common in both age groups, though women of reproductive age are more likely to report it. Heightened somatic awareness may be more strongly associated with CPP in older women. There are distinct groups of CPP cases characterized by the absence/presence of psychosocial distress.
Heightened somatic awareness may be more strongly associated with CPP in women of post-reproductive years compared to women of reproductive years. Two subgroups of CPP cases can be differentiated by the absence/presence of psychosocial distress suggesting that stratified management approach may be more efficient.
Neuropathic pain is a debilitating condition with no adequate therapy. The health benefits of omega-3 fatty acids are established, however, the role of docosahexaenoic acid (DHA) in limiting pain has only recently been described and the mechanisms of this action remain unknown. DHA is metabolized into epoxydocosapentanoic acids (EDPs) via cytochrome P450 (CYP450) enzymes which are substrates for the soluble epoxide hydrolase (sEH) enzyme. Here, we tested several hypotheses; first, that the antinociceptive action of DHA is mediated by the EDPs. Second, based on evidence that DHA and CYP450 metabolites elicit analgesia through opioid signalling, we investigated this as a possible mechanism of action. Third, we tested whether the analgesia mediated by epoxy fatty acids had similar rewarding effects as opioid analgesics.
We tested diabetic neuropathic wild-type and sEH null mice in a conditioned place preference assay for their response to EDPs, sEHI and antagonism of these treatments with naloxone, a mu-opioid receptor antagonist.
The EDPs and sEH inhibitors were efficacious against chronic pain, and naloxone antagonized the action of both EDPs and sEH inhibitors. Despite this antagonism, the sEH inhibitors lacked reward side effects differing from opioids.
The EpFA are analgesic against chronic pain differing from opioids which have limited efficacy in chronic conditions.
EDPs and sEHI mediate analgesia in modelled chronic pain and this analgesia is blocked by naloxone. However, unlike opioids, sEHI are highly effective in neuropathic pain models and importantly lack rewarding side effects.
Study Design. A prospective, single-arm, pre-postintervention study. Objective. The aim of this study was to test the preliminary effectiveness of a patient-led goal-setting intervention on improving disability and pain in chronic low back pain. Summary of Background Data. An effective intervention for the treatment of chronic low back pain remains elusive despite extensive research into the area. An intervention using patient-centered goal setting to drive intervention strategies and encourage self-management for patients suffering chronic low back was developed. Methods. A single group longitudinal cohort pilot study was conducted. Twenty participants (male = nine) experiencing chronic low back pain were involved in a patient-led goal-setting intervention, facilitated by a physiotherapist over a 2-month period with two monthly follow-up sessions after treatment conclusion. Participants, guided by the therapist, identified problem areas of personal importance, defined goals, and developed evidence-based strategies to achieve the goals. Participants implemented the strategies independently between sessions. Primary outcome measures of disability and pain intensity were measured at baseline, 2, and 4 months. Secondary measures of quality of life, stress and anxiety, self-efficacy, and fear of movement were also taken. Results. Significant improvements (repeated analysis of variance P < 0.05) were seen in measures of disability, pain, fear avoidance, quality of life, and self-efficacy over the period of intervention and were maintained for a further 2 months after treatment conclusion. Conclusion. This intervention is novel because the goals set are based on patients’ personal preferences, and not on treatment guidelines. Our findings confirm that a patient-centered goal-setting intervention is a potentially effective intervention for the management of chronic low back pain showing significant improvements in both quality of life and pain intensity. Level of Evidence: 4
Study Design. Experimental randomized crossover. Objective. The aim of the study was to determine whether sitting on a ball for 90 min/d instead of a chair has an effect on low back pain (LBP), low back disability, and/or core muscle endurance. Summary of Background Data. LBP may result from prolonged sitting. It has been proposed that replacing chairs with stability balls can diminish LBP in those who sit for prolonged periods. Research on the topic is sparse and inconclusive. Methods. A total of 90 subjects (university students, staff, and faculty, ages 18–65, who sit ≥4 hr/d) were randomly assigned to the intervention or control group for the first part of the study. Baseline data were collected: Oswestry Disability Index, a numerical pain rating scale for LBP, and four core muscle endurance tests. For 8 weeks, the control group sat on their usual chair. The intervention group sat on stability balls 5 d/wk, increasing up to 90 min/d. Baseline measurements were repeated postintervention. After a washout period, subjects switched groups, and the procedures were repeated—70 completed participation in control group and 76 in intervention group. Results. There were no statistically significant differences for pain or disability in either group (P > 0.05). Changes in isometric trunk flexion (P = 0.001), nondominant side plank (P = 0.008), and Sorensen (P = 0.006) endurance scores were significant within the intervention group but not the control group. Between-group comparisons revealed a significant difference for isometric trunk flexion (P = 0.005) and Sorensen endurance times (P = 0.010). Analysis also showed that ball-sitting did not prevent an increase in LBP over the 8-week period. Conclusion. Ball-sitting had no significant effects on LBP or associated disability, but did improve core endurance in the sagittal plane. Although ball-sitting may be useful as an adjunct treatment for LBP when core muscles are involved, clinicians should rely on other, evidence-based treatments for LBP. Level of Evidence: 2
Study Design. A retrospective study. Objective. The aim of this study is to evaluate, clinically and radiographically, the efficacy of mini-open retroperitoneal anterior lumbar discectomy followed by anterior lumbar interbody fusion (ALIF) for recurrent lumbar disc herniation following primary posterior instrumentation. Summary of Background Data. Recurrent disc herniation following previous disc surgery occurs in 5 to 15% of cases. This is often treated by further surgical intervention where posterior approach is generally preferred. However, posterior surgery may be problematic if the initial surgery involved posterior instrumentation. An anterior approach may be indicated in these patients, and recent findings suggest that a “mini-open” procedure may have some benefits when compared with traditional open techniques and their associated morbidities. Methods. A total of 35 recurrent lumbar disc herniation patients (10 male, 25 female) following primary posterior instrumentation with an average age of 52.8 years (range: 34–70 yrs) who underwent the mini-open ALIF procedures between August 2001 and February 2012 were evaluated retrospectively. The ALIF was performed at the levels L4-L5 (n = 14), L5-S1 (n = 15), or both L4-L5 and L5-S1 (n = 6). Visual Analog pain Scale (VAS) and Oswestry Disability Index (ODI) together with radiological results were assessed. Results. The mean operating time, intraoperative estimated blood loss, and hospital stay were 115 minutes, 70 mL, and 6 days, respectively. No blood transfusion was needed. Transient complication was recorded in two patients. Postoperative follow-up was a minimum 24.3 months. VAS score and ODI percentage decreased significantly from 7.9 ± 0.8 and 78.8% ± 12.4% pre-operatively to 1.4 ± 0.6 and 21.7 ± 4.2% at final follow-up, respectively. There was no neurological worsening and radicular pain improved significantly compared with pre-operation in all the patients. Computed tomographic reconstruction 12 and 24 months after surgery showed bony fusion, normal position, and morphology of the fusion cage in all patients. Conclusion. Mini-open retroperitoneal ALIF is an effective treatment for patients with recurrent lumbar disc herniation following primary posterior instrumentation. Level of Evidence: 4
Study Design. Retrospective case series. Objective. To describe a modified technique for mini-open transforaminal lumbar interbody fusion (TLIF) that improves visualization for decompression, fusion, and freehand pedicle screw insertion. Accuracy of freehand pedicle screw placement with this technique was assessed. Summary of Background Data. Mini-open TLIF is a minimally invasive technique that allows limited visualization of the bone and neural anatomy via an expandable tubular retractor inserted through the Wiltse plane. No significant modification that of this technique has been described in detail. Methods. In this study, 92 consecutive patients underwent one-level modified mini-open TLIF (MOTLIF). MOTLIF modifications consisted of (i) transmuscular dissection through the multifidus muscle rather than intermuscular dissection in the Wiltse plane; (ii) microsurgical detachment of multifidus from the facet rather than muscle dilation; (iii) en bloc total facetectomy (unilateral or bilateral, as needed for decompression); (iv) facet autograft used for interbody fusion; and (v) solid pedicle screws placed bilaterally by a freehand technique under direct vision. Results. The mean age was 53 years. Mean follow-up was 35 months (minimum 2 yrs). By 6 months, mean Visual Analog Scale for back and leg pain had improved from 51 to 19 and from 58 to 17, respectively, and mean Oswestry Disability Index (ODI) improved from 53 to 16. These improvements persisted at 2 years. Solid fusion, defined by computed tomography at 1 year, was achieved in 88.1%, whereas satisfactory fusion was achieved in 95.2% of patients. Pedicle screws were accurately placed in 335 of 336 imaged pedicles (pedicle breach grades: 91.1% grade 1; 8.6% grade 2; and 0.3% grade 3). Mean fluoroscopy time was 29.3 seconds. Conclusion. MOTLIF is a safe and effective minimally invasive technique with a high fusion rate. It allows accurate pedicle screw placement by a freehand technique. By eliminating bi-planar fluoroscopy, it helps reduce radiation exposure. This is the largest published report of mini-open TLIF to date. Level of Evidence: 4 
Study Design. A retrospective cohort study. Objective. The objective of this study is to compare the radiographic and clinical outcomes of transforaminal lumbar interbody fusion (TLIF) with bilateral facetectomy (BF) versus unilateral facetectomy (UF). Summary of Background Data. BF is a surgical technique utilized with the intent of creating a greater degree of segmental lordosis than UF alone. However, the clinical benefits of this technique have not been defined. We seek to determine whether a difference exists between bilateral versus UF during TLIF by utilizing both clinical and radiographic outcome measures. Methods. The electronic medical records of 57 patients who underwent single-level TLIF with either a UF (n = 28) or BF (n = 29) were reviewed. Clinical outcomes were measured through Patient Health Questionnaire-9 (PHQ-9), Pain Disability Questionnaire (PDQ), EuroQol 5 Dimensions (EQ-5D) Health State, and Quality Adjusted Life Year (QALY). Radiographic parameters including disc height and sagittal balance were measured on plain radiographs at 1 year following operation. Results. All radiographic parameters showed no significant differences between the UF and BF cohorts. Segmental lordosis increased significantly in both cohorts. However, there was no significant difference in the increase of segmental lordosis between cohorts. Overall lumbar lordosis did not increase significantly in either cohort. Perioperative complications were also similar between cohorts. PDQ and EQ-5D scores improved significantly in both cohorts at 1 year postoperatively. The BF cohort showed a significantly greater improvement in both EQ-5D (0.1 ± 0.2 vs. 0.3 ± 0.2, P = 0.01) and PHQ-9 scores (-0.8 ± 4.6 vs. 4.6 ± 5.2, P = 0.03) than the UF cohort. The PDQ score improved over the minimally clinical important difference (MCID) of 26 in only the BF cohort. Conclusion. The findings in the present study demonstrate that BF during single-level TLIF improves clinical outcomes to a greater degree than UF without any notable differences in perioperative complications or radiographic measurements. Level of Evidence: 3
Study Design. A population-based cross-sectional survey. Objective. The aim of this study was to compare the prevalence of illicit drug use among US adults with and without chronic low back pain (cLBP). Summary of Background Data. Although addictive medications, such as opioids and benzodiazepines, are frequently prescribed to patients with cLBP, little is known about illicit drug use among Americans with cLBP. Methods. We used data from the back pain survey, administered to a representative sample of US adults aged 20 to 69 years (N = 5103) during the 2009 to 2010 cycle of the National Health and Nutrition Examination Survey (NHANES). Participants with pain in the area between the lower posterior margin of the ribcage and the horizontal gluteal fold for at least 3 months were classified as having cLBP (N = 700). The drug use questionnaire was self-administered in a private setting, and included data on lifetime and current use of marijuana or hashish, cocaine, heroin, and methamphetamine. Chi-square tests, one-way analysis of variance, and logistic regression, adjusted for age, gender, race, and level of education, were used for comparisons. Results. About 46.5% of US adults with cLBP used marijuana versus 42% of those without cLBP [Adjusted odds ratio (aOR) 1.36, 95% confidence interval (95% CI) 1.06–1.74]. About 22% versus 14% used cocaine (aOR 1.80, 95% CI 1.45–2.24), 9% versus 5% used methamphetamine (aOR 2.03, 95% CI 1.30–3.16), and 5% versus 2% used heroin (aOR 2.43, 95% CI 1.44–4.11). Subjects with cLBP who reported lifetime illicit drug use were more likely to have an active prescription for opioid analgesics than those without illicit drug use history: 22.5% versus 15.3%, P = 0.018. Conclusion. cLBP in community-based US adults was associated with higher odds of using marijuana, cocaine, heroin, and methamphetamine. Prescription opioid analgesic use was more common in cLBP sufferers with a history of illicit drug use. Level of Evidence: 2
Study Design. A prospective multicenter cohort study. Objective. The aim of this study was to identify an association between pain and magnetic resonance imaging (MRI) parameters in patients with lumbar spinal stenosis (LSS). Summary of Background Data. At present, the relationship between abnormal MRI findings and pain in patients with LSS is still unclear. Methods. First, we conducted a systematic literature search. We identified relationships of relevant MRI parameters and pain in patients with LSS. Second, we addressed the study question with a thorough descriptive and graphical analysis to establish a relationship between MRI parameters and pain using data of the LSS outcome study (LSOS). Results. In the systematic review including four papers about the associations between radiological findings in the MRI and pain, the authors of two articles reported no association and two of them did. Of the latters, only one study found a moderate correlation between leg pain measured by Visual Analog Scale (VAS) and the degree of stenosis assessed by spine surgeons. In the data of the LSOS study, we could not identify a relevant association between any of the MRI parameters and buttock, leg, and back pain, quantified by the Spinal Stenosis Measure (SSM) and the Numeric Rating Scale (NRS). Even by restricting the analysis to the level of the lumbar spine with the most prominent radiological “stenosis,” no relevant association could be shown. Conclusion. Despite a thorough analysis of the data, we were not able to prove any correlation between radiological findings (MRI) and the severity of pain. There is a need for innovative “methods/techniques” to learn more about the causal relationship between radiological findings and the patients’ pain-related complaints. Level of Evidence: 2
