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1.  Somatosensory Abnormalities for Painful and Innocuous Stimuli at the Back and at a Site Distinct from the Region of Pain in Chronic Back Pain Patients 
PLoS ONE  2013;8(3):e58885.
Chronic low back pain (CLBP) was shown to be associated with pathophysiological changes at several levels of the sensorimotor system. Changes in sensory thresholds have been reported but complete profiles of Quantitative Sensory Testing (QST) were only rarely obtained in CLBP patients. The aim of the present study was to investigate comprehensive QST profiles in CLBP at the painful site (back) and at a site distinct from their painful region (hand) and to compare these data with similar data in healthy controls. We found increased detection thresholds in CLBP patients compared to healthy controls for all innocuous stimuli at the back and extraterritorial to the painful region at the hand. Additionally, CLBP patients showed decreased pain thresholds at both sites. Importantly, there was no interaction between the investigated site and group, i.e. thresholds were changed both at the affected body site and for the site distinct from the painful region (hand). Our results demonstrate severe, widespread changes in somatosensory sensitivity in CLBP patients. These widespread changes point to alterations at higher levels of the neuraxis or/and to a vulnerability to nociceptive plasticity in CLBP patients.
PMCID: PMC3598908  PMID: 23554950
2.  Influence of comorbidity with depression on interdisciplinary therapy: outcomes in patients with chronic low back pain 
Arthritis Research & Therapy  2010;12(5):R185.
Our previous work showed higher tumour necrosis factor (TNF)-α levels in patients with chronic low back pain (cLBP) compared to healthy controls. However, patients with depression as a comorbidity did not have higher TNF-α levels in comparison to patients without depression. In this study we investigated the influence of depression on therapy outcomes such as TNF-α serum levels, pain intensity and back function in patients with cLBP. Our hypothesis was that patients with both cLBP and depression benefit no less than patients with cLBP alone from the multidisciplinary pain therapy.
A total of 58 patients with cLBP alone or with both cLBP and depression were age- and sex-matched with 29 healthy controls. Serum concentrations of TNF-α were assayed at the beginning of the study (T0) and 10 days (T1), 21 days (T2), and 180 days (T3) later. The clinical outcomes such as pain intensity, as well as back function, sleep, exercise, alcohol and nicotine consumption were documented. In the first three weeks, all patients underwent multidisciplinary therapy based upon biological, psychological, physical and psychosocial components.
Over the whole course there were no differences in TNF-α level between cLBP patients with and without depression. At T0, both cLBP patients with (cLBP+DE) and without (cLBP) depression showed significantly higher TNF-α serum levels (P = 0.002 for cLBP+DE, P = 0.004 for cLBP) than healthy controls (HC) that normalized after 10 days of therapy and remained similar to healthy controls. During the follow-up, the depression scales were normalised and pain intensity was significantly reduced. Both evidences processed parallel to the reduction of TNF-α levels, which correlates neither with depression score nor with pain intensity at any time point.
Depression as a comorbidity to chronic low back pain did not influence the serum TNF-α level in the course of six months, but seemed to affect the success of therapy. cLBP patients with comorbidity of depression benefit from multidisciplinary pain therapy not only to the same extent but also to a greater degree than cLBP patients without depression.
PMCID: PMC2991020  PMID: 20937108
3.  Exercise and manual auricular acupuncture: a pilot assessor-blind randomised controlled trial. (The acupuncture and personalised exercise programme (APEP) Trial) 
Evidence supports the use of exercise for chronic low back pain (CLBP); however, adherence is often poor due to ongoing pain. Auricular acupuncture is a form of pain relief involving the stimulation of points on the outer ear corresponding with specific body parts. It may be a useful adjunct to exercise in managing CLBP; however, there is only limited evidence to support its use with this patient group.
This study was designed to test the feasibility of an assessor-blind randomised controlled trial which assess the effects on clinical outcomes and exercise adherence of adding manual auricular acupuncture to a personalised and supervised exercise programme (PEP) for CLBP. No sample size calculation has been carried out as this study aims to identify CLBP referral rates within the catchment area of the study site. The researchers aim to recruit four cohorts of n = 20 participants to facilitate a power analysis for a future randomised controlled trial. A computer generated random allocation sequence will be prepared centrally and used to allocate participants by cohort to one of the following interventions: 1) six weeks of PEP plus manual auricular acupuncture; 2) six weeks of PEP alone. Both groups will also complete a further six weeks of self-paced exercise with telephone follow-up support. In addition to a baseline and exit questionnaire at the beginning and end of the study, the following outcomes will be collected at baseline, and after 7, 13 and 25 weeks: pain frequency and bothersomeness, back-specific function, objective assessment and recall of physical activity, use of analgesia, perceived self-efficacy, fear avoidance beliefs, and beliefs about the consequences of back pain. Since this is a feasibility study, significance tests will not be presented, and treatment effects will be represented by point estimates and confidence intervals. For each outcome variable, analysis of covariance will be performed on the data, conditioning on the baseline value.
The results of this study investigating the adjuvant effects of auricular acupuncture to exercise in managing CLBP will be used to inform the design of a future multi-centre randomised controlled trial.
Trial Registration
Current Controlled Trials ISRCTN94142364.
PMCID: PMC2322991  PMID: 18325114
4.  Disrupted functional connectivity of the periaqueductal gray in chronic low back pain 
NeuroImage : Clinical  2014;6:100-108.
Chronic low back pain is a common neurological disorder. The periaqueductal gray (PAG) plays a key role in the descending modulation of pain. In this study, we investigated brain resting state PAG functional connectivity (FC) differences between patients with chronic low back pain (cLBP) in low pain or high pain condition and matched healthy controls (HCs). PAG seed based functional connectivity (FC) analysis of the functional MR imaging data was performed to investigate the difference among the connectivity maps in the cLBP in the low or high pain condition and HC groups as well as within the cLBP at differing endogenous back pain intensities. Results showed that FC between the PAG and the ventral medial prefrontal cortex (vmPFC)/rostral anterior cingulate cortex (rACC) increased in cLBP patients compared to matched controls. In addition, we also found significant negative correlations between pain ratings and PAG–vmPFC/rACC FC in cLBP patients after pain-inducing maneuver. The duration of cLBP was negatively correlated with PAG–insula and PAG–amygdala FC before pain-inducing maneuver in the patient group. These findings are in line with the impairments of the descending pain modulation reported in patients with cLBP. Our results provide evidence showing that cLBP patients have abnormal FC in PAG centered pain modulation network during rest.
Our results provide evidence showing that cLBP patients have abnormal FC in PAG centered pain modulation network during rest, which might have important treatment implications.
•cLBP patients exhibited enhanced PAG–mPFC coupling.•cLBP duration was correlated with PAG–mPFC coupling.•Pain intensity was correlated with PAG–insula and PAG–amygdala coupling.
PMCID: PMC4215524  PMID: 25379421
Chronic low back pain; fMRI; Functional connectivity; Periaqueductal gray
5.  Differences across health care systems in outcome and cost-utility of surgical and conservative treatment of chronic low back pain: a study protocol 
There is little evidence on differences across health care systems in choice and outcome of the treatment of chronic low back pain (CLBP) with spinal surgery and conservative treatment as the main options. At least six randomised controlled trials comparing these two options have been performed; they show conflicting results without clear-cut evidence for superior effectiveness of any of the evaluated interventions and could not address whether treatment effect varied across patient subgroups. Cost-utility analyses display inconsistent results when comparing surgical and conservative treatment of CLBP. Due to its higher feasibility, we chose to conduct a prospective observational cohort study.
This study aims to examine if
1. Differences across health care systems result in different treatment outcomes of surgical and conservative treatment of CLBP
2. Patient characteristics (work-related, psychological factors, etc.) and co-interventions (physiotherapy, cognitive behavioural therapy, return-to-work programs, etc.) modify the outcome of treatment for CLBP
3. Cost-utility in terms of quality-adjusted life years differs between surgical and conservative treatment of CLBP.
This study will recruit 1000 patients from orthopaedic spine units, rehabilitation centres, and pain clinics in Switzerland and New Zealand. Effectiveness will be measured by the Oswestry Disability Index (ODI) at baseline and after six months. The change in ODI will be the primary endpoint of this study.
Multiple linear regression models will be used, with the change in ODI from baseline to six months as the dependent variable and the type of health care system, type of treatment, patient characteristics, and co-interventions as independent variables. Interactions will be incorporated between type of treatment and different co-interventions and patient characteristics. Cost-utility will be measured with an index based on EQol-5D in combination with cost data.
This study will provide evidence if differences across health care systems in the outcome of treatment of CLBP exist. It will classify patients with CLBP into different clinical subgroups and help to identify specific target groups who might benefit from specific surgical or conservative interventions. Furthermore, cost-utility differences will be identified for different groups of patients with CLBP. Main results of this study should be replicated in future studies on CLBP.
PMCID: PMC2438357  PMID: 18534034
6.  MALDI-TOF-MS serum protein profiling for developing diagnostic models and identifying serum markers for discogenic low back pain 
The identification of the cause of chronic low back pain (CLBP) represents a great challenge to orthopedists due to the controversy over the diagnosis of discogenic low back pain (DLBP) and the existence of a number of cases of CLBP of unknown origin. This study aimed to develop diagnostic models to distinguish DLBP from other forms of CLBP and to identify serum biomarkers for DLBP.
Serum samples were collected from patients with DLBP, chronic lumbar disc herniation (LDH), or CLBP of unknown origin, and healthy controls (N), and randomly divided into a training set (n = 30) and a blind test set (n = 30). Matrix-assisted laser desorption ionization time-of-flight mass spectrometry was performed for protein profiling of these samples. After the discriminative ability of two most significantly differential peaks from each two groups was assessed using scatter plots, classification models were developed using differential peptide peaks to evaluate their diagnostic accuracy. The identity of peptides corresponding to three representative differential peaks was analyzed.
The fewest statistically significant differential peaks were identified between DLBP and CLBP (3), followed by CLBP vs. N (5), DLBP vs. N (9), LDH vs. CLBP (20), DLBP vs. LDH (23), and LDH vs. N (43). The discriminative ability of two most significantly differential peaks was poor in classifying DLBP vs. CLBP but good in classifying DLBP vs. LDH. The accuracy of models for classification of DLBP vs. CLBP was not very high in the blind test (forecasting ability, 67.24%; sensitivity, 70%), although a higher accuracy was observed for classification of DLBP vs. LDH and LDH vs. N (forecasting abilities, ~90%; sensitivities, >90%). A further investigation of three representative differential peaks led to the identification of two peaks as peptides of complement C3, and one peak as a human fibrinogen peptide.
Our findings benefit not only the diagnosis of CLBP but also the understanding of the differences between different forms of DLBP. The ability to distinguish between different causes of CLBP and the identification of serum biomarkers may be of great value to diagnose different causes of DLBP and predict treatment efficacy.
PMCID: PMC4061098  PMID: 24889399
Chronic low back pain; Dicogenic low back pain; Lumbar disc herniation; MALDI-TOF-MS; Serum profiling; Biomarker
7.  S1 is associated with chronic low back pain: a functional and structural MRI study 
Molecular Pain  2013;9:43.
A fundamental characteristic of neural circuits is the capacity for plasticity in response to experience. Neural plasticity is associated with the development of chronic pain disorders. In this study, we investigated 1) brain resting state functional connectivity (FC) differences between patients with chronic low back pain (cLBP) and matched healthy controls (HC); 2) FC differences within the cLBP patients as they experienced different levels of endogenous low back pain evoked by exercise maneuvers, and 3) morphometric differences between cLBP patients and matched HC. We found the dynamic character of FC in the primary somatosensory cortex (S1) in cLBP patients, i.e., S1 FC decreased when the patients experienced low intensity LBP as compared with matched healthy controls, and FC at S1 increased when cLBP patients experienced high intensity LBP as compared with the low intensity condition. In addition, we also found increased cortical thickness in the bilateral S1 somatotopically associated with the lower back in cLBP patients as compared to healthy controls. Our results provide evidence of structural plasticity co-localized with areas exhibiting FC changes in S1 in cLBP patients.
PMCID: PMC3765748  PMID: 23965184
Chronic low back pain; fMRI; Functional connectivity; Cortical thickness; Primary somatosensory cortex
8.  Quality of sleep in patients with chronic low back pain: a case-control study 
European Spine Journal  2008;17(6):839-844.
Animal experiments and studies in humans clearly show that the relation between pain (acute and chronic) and sleep quality is two-way: sleep disorders can increase pain, which in turn may cause sleep disorders. Sleep disorders and chronic low back pain are frequent health problems and it is unsurprising that the two can co-exist. This study was conducted to evaluate if sleep disorders and chronic pain associated are more frequently than one would expect. The objective of the study was to compare sleep quality in a population of patients with chronic low back pain and a control population. Sleep quality was assessed in 101 patients with chronic low back pain (CLBP) and in 97 sex- and age-matched healthy control subjects using the Pittsburgh Sleep Quality Index [PSQI; score from 0 (no disorder) to 21]. The French version of the Dallas Pain Questionnaire (DPQ) was used to assess the impact of low back pain on patients’ quality of life. This impact was taken as nil in the healthy controls. The patients with CLBP and the controls were comparable in age, sex, and height, but mean bodyweight was higher in the CLBP group (70.3 ± 14.5 vs. 61.8 ± 11.4 kg; P < 0.05). The patients with CLBP were also more frequently on sick leave than the controls (32.3%; n = 31 vs. 0.0% n = 0; P < 0.001). Coffee, tea, and cola intakes were comparable in the two groups. Patients with CLBP had statistically higher scores in all items of the PSQI than the healthy controls. The mean PSQI was 4.7 ± 3.2 for the healthy controls and 10.9 ± 7.9 for the patients with CLBP (P < 0.0001). Sleep disorders were greater when the impact of CLBP on daily life (the four aspects of the DPQ) was greater [P < 0.0001]). The sleep of the patients with CLBP was significantly altered compared with that of the healthy controls, in proportion to the impact of low back pain on daily life. Our findings do not indicate whether sleep disorders are a cause or a consequence of CLBP.
PMCID: PMC2518999  PMID: 18389288
Chronic low back pain; Sleep disorders; Dallas Pain Questionnaire; Pittsburgh Sleep Quality Index; Case control study
9.  White Matter Hyperintensity Burden and Disability in Older Adults: Is Chronic Pain a Contributor? 
To primarily explore differences in global and regional white matter hyper-intensities (WMH) in older adults with self-reported disabling and nondisabling chronic low back pain (CLBP) and to examine the association of WMH with gait speed in all participants with CLBP. To secondarily compare WMH of the participants with CLBP with the pain-free controls.
A cross-sectional, case-control study.
University of Pittsburgh.
Twenty-four community-dwelling older adults: 8 with self-reported disabling CLBP, 8 with nondisabling CLBP, and 8 were pain-free. Exclusions were psychiatric or neurologic disorders (either central or peripheral), substance abuse, opioid use, or diabetes mellitus.
All participants underwent structural brain magnetic resonance imaging, and all participants with CLBP underwent the 4-m walk test.
Main Outcome Measurements
All the participants were assessed for both global and regional WMH by using an automated localization and segmentation method, and gait speed of participants with CLBP.
The disabled group demonstrated statistically significant regional WMH in a number of left hemispheric tracts: anterior thalamic radiation (P = .0391), lower cingulate (P = .0336), inferior longitudinal fasciculus (P = .0367), superior longitudinal fasciculus (P=.0011), and the superior longitudinal fasciculus branch to the temporal lobe (P=.0072). Also, there was a statistically significant negative association (rs = −0.57; P = .0225) between the left lower cingulate WMH and the gait speed in all the participants with CLBP. There was a statistical difference in global WMH burden (P=.0014) and nearly all regional tracts (both left and right hemispheres) when comparing CLBP with pain-free participants.
Our findings suggest that WMH is associated with, and hence, may be accelerated by chronic pain manifesting as perceived disability, given the self-reported disabled CLBP patients had the greatest burden, and the pain free the least, and manifesting as measurable disability, given increasing WMH was associated with decreasing gait speed in all chronic pain participants.
PMCID: PMC4023475  PMID: 23474209
10.  Consumers’ experiences of back pain in rural Western Australia: access to information and services, and self-management behaviours 
Coordinated, interdisciplinary services, supported by self-management underpin effective management for chronic low back pain (CLBP). However, a combination of system, provider and consumer-based barriers exist which limit the implementation of such models into practice, particularly in rural areas where unique access issues exist. In order to improve health service delivery for consumers with CLBP, policymakers and service providers require a more in depth understanding of these issues. The objective of this qualitative study was to explore barriers experienced by consumers in rural settings in Western Australia (WA) to accessing information and services and implementing effective self-management behaviours for CLBP.
Fourteen consumers with a history of CLBP from three rural sites in WA participated. Maximum variation sampling was employed to ensure a range of experiences were captured. An interviewer, blinded to quantitative pain history data, conducted semi-structured telephone interviews using a standardised schedule to explore individuals’ access to information and services for CLBP, and self-management behaviours. Interviews were digitally recorded and transcribed verbatim. Inductive analysis techniques were used to derive and refine key themes.
Five key themes were identified that affected individuals’ experiences of managing CLBP in a rural setting, including: 1) poor access to information and services in rural settings; 2) inadequate knowledge and skills among local practitioners; 3) feelings of isolation and frustration; 4) psychological burden associated with CLBP; and 5) competing lifestyle demands hindering effective self-management for CLBP.
Consumers in rural WA experienced difficulties in knowing where to access relevant information for CLBP and expressed frustration with the lack of service delivery options to access interdisciplinary and specialist services for CLBP. Competing lifestyle demands such as work and family commitments were cited as key barriers to adopting regular self-management practices. Consumer expectations for improved health service coordination and a workforce skilled in pain management are relevant to future service planning, particularly in the contexts of workforce capacity, community health services, and enablers to effective service delivery in primary care.
PMCID: PMC3494578  PMID: 23057669
Back pain; Qualitative; Education; Policy; Health services; Self-management; Rural
11.  Motor performance in chronic low back pain: is there an influence of pain-related cognitions? A pilot study 
Chronic low back pain (CLBP) is often accompanied by an abnormal motor performance. However, it has not been clarified yet whether these deviations also occur during motor tasks not involving the back and whether the performance is influenced by pain and pain-related cognitions. Therefore, the aim of the present study is to get insight in the contribution of both pain experience and pain-related cognitions to general motor task performance in CLBP.
13 CLBP patients and 15 healthy subjects performed a hand-function task in three conditions: sitting, lying prone (lying) and lying prone without trunk support (provoking). The last condition was assumed to provoke pain-related cognitions, which was considered successful when a patients' pain expectancy on a numeric rating scale was at least 1 point higher than actual pain experienced. Subjects' performance was expressed in reaction time and movement time. Repeated measures analysis of variance was performed to detect main effect for group and condition. Special interest was given to group*condition interaction, since significant interaction would indicate that patients and healthy subjects performed differently throughout the three conditions.
Patients were slower throughout all conditions compared to healthy subjects. With respect to the provoking condition, patients showed deteriorated performance compared to lying while healthy subjects' performance remained equal between these two conditions. Further analysis of patients' data showed that provocation was successful in 54% of the patients. Especially this group showed deteriorated performance in the provoking condition.
It can be concluded that CLBP patients in general have worse motor task performance compared to healthy subjects and that provoking pain-related cognitions further worsened performance.
PMCID: PMC3196736  PMID: 21951591
chronic low back pain; movement speed; reaction time; pain-related cognitions
12.  Cognition and emotional decision-making in chronic low back pain: an ERPs study during Iowa gambling task 
Frontiers in Psychology  2014;5:1350.
Previous reports documented abnormalities in cognitive functions and decision-making (DM) in patients with chronic pain, but these changes are not consistent across studies. Reasons for these discordant findings might include the presence of confounders, variability in chronic pain conditions, and the use of different cognitive tests. The present study was aimed to add evidence in this field, by exploring the cognitive profile of a specific type of chronic pain, i.e., chronic low back pain (cLBP). Twenty four cLBP patients and 24 healthy controls underwent a neuropsychological battery and we focused on emotional DM abilities by means of Iowa gambling task (IGT). During IGT, behavioral responses and the electroencephalogram (EEG) were recorded in 12 patients and 12 controls. Event-related potentials (ERPs) were averaged offline from EEG epochs locked to the feedback presentation (4000 ms duration, from 2000 ms before to 2000 ms after the feedback onset) separately for wins and losses and the feedback-related negativity (FRN) and P300 peak-to-peak amplitudes were calculated. Among cognitive measures, cLBP patients scored lower than controls in the modified card sorting test (MCST) and the score in this test was significantly influenced by pain duration and intensity. Behavioral IGT results documented worse performance and the absence of a learning process during the test in cLBP patients compared to controls, with no effect of pain characteristics. ERPs findings documented abnormal feedback processing in patients during IGT. cLBP patients showed poor performance in the MCST and the IGT. Abnormal feedback processing may be secondary to impingement of chronic pain in brain areas involved in DM or suggest the presence of a predisposing factor related to pain chronification. These abnormalities might contribute to the impairment in the work and family settings that often cLBP patients report.
PMCID: PMC4243494  PMID: 25505440
chronic pain; Iowa gambling task (IGT); decision-making; event-related potentials (ERPs); low back pain
13.  Influence of depression symptoms on serum tumor necrosis factor-α of patients with chronic low back pain 
Arthritis Research & Therapy  2010;12(5):R186.
Patients with chronic low back pain (cLBP) have high rates of comorbid psychiatric disorders, mainly depression. Recent evidence suggests that depressive symptoms and pain, as interacting factors, have an effect on the circulating levels of inflammatory markers relevant to coronary artery disease. Our previous work showed a higher serum level of an inflammatory marker tumour necrosis factor-alpha (TNFα) in patients with cLBP, which did not correlate with intensity of low back pain alone. In the present study we investigated the cross-sectional associations of depressive symptoms, low back pain and their interaction with circulating levels of TNFα.
Each group of 29 patients with cLBP alone or with both cLBP and depression was age-matched and sex-matched with 29 healthy controls. All subjects underwent a blood draw for the assessment of serum TNFα and completed a standardised questionnaire regarding medication, depression scores according to the German version of Centre for Epidemiological Studies Depression Scale (CES-D), pain intensity from a visual analogue scale, and back function using the Roland and Morris questionnaire. The correlations between TNFα level and these clinical parameters were analysed.
There were no differences in TNFα level between cLBP patients with and without depression. Both cLBP patients with (median = 2.51 pg/ml, P = 0.002) and without (median = 2.58 pg/ml, P = 0.004) depression showed significantly higher TNFα serum levels than healthy controls (median = 0 pg/ml). The pain intensity reported by both patient groups was similar, while the patients with depression had higher CES-D scores (P < 0.001) and worse back function (P < 0.001). The variance analysis showed that the interaction between TNFα level and pain intensity, CES-D scores, sex, body mass index and medication was statistically significant.
Depression as a comorbidity to cLBP did not influence the serum TNFα level. It seems that TNFα somehow acts as a mediator in both cLBP and depression, involving similar mechanisms that will be interesting to follow in further studies.
PMCID: PMC2991021  PMID: 20937109
14.  Objective and subjective assessment of sleep in chronic low back pain patients compared with healthy age and gender matched controls: a pilot study 
While approximately 70% of chronic low back pain (CLBP) sufferers complain of sleep disturbance, current literature is based on self report measures which can be prone to bias and no objective data of sleep quality, based exclusively on CLBP are available. In accordance with the recommendations of The American Sleep Academy, when measuring sleep, both subjective and objective assessments should be considered as the two are only modestly correlated, suggesting that each modality assesses different aspects of an individual's sleep experience. Therefore, the purpose of this study was to expand previous research into sleep disturbance in CLBP by comparing objective and subjective sleep quality in participants with CLBP and healthy age and gender matched controls, to identify correlates of poor sleep and to test logistics and gather information prior to a larger study.
15 CLBP participants (mean age = 43.8 years (SD = 11.5), 53% female) and 15 healthy controls (mean age = 41.5 years (SD = 10.6), 53% female) consented. All participants completed the Pittsburgh Sleep Quality Index, Insomnia Severity Index, Pittsburgh Sleep Diary and the SF36v2. CLBP participants also completed the Oswestry Disability Index. Sleep patterns were assessed over three consecutive nights using actigraphy. Total sleep time (TST), sleep efficiency (SE), sleep latency onset (SL) and number of awakenings after sleep onset (WASO) were derived. Statistical analysis was conducted using unrelated t-tests and Pearson's product moment correlation co-efficients.
CLBP participants demonstrated significantly poorer overall sleep both objectively and subjectively. They demonstrated lower actigraphic SE (p = .002) and increased WASO (p = .027) but no significant differences were found in TST (p = .43) or SL (p = .97). Subjectively, they reported increased insomnia (p =< .001), lower SE (p =< .001) and increased SL (p =< .001) but no difference between TST (p = .827) and WASO (p = .055). Statistically significant associations were found between low back pain (p = .021, r = -.589), physical health (p = .003, r = -.713), disability levels (p = .025, r = .576), and subjective sleep quality in the CLBP participants but not with actigraphy.
CLBP participants demonstrated poorer overall sleep, increased insomnia symptoms and less efficient sleep. Further investigation using a larger sample size and a longer period of sleep monitoring is ongoing.
PMCID: PMC2765952  PMID: 19799778
15.  Short-term response of hip mobilizations and exercise in individuals with chronic low back pain: a case series 
Study design
A case series of consecutive patients with chronic low back pain.
Background and purpose
In patients with chronic low back pain (CLBP), the importance of impairments at the hip joints is unclear. However, it has been postulated that impairments at the hip joints may contribute to CLBP. The purpose of this case series was to investigate the short-term outcomes in patients with CLBP managed with impairment-based manual therapy and exercise directed at the hip joints.
Eight consecutive patients (mean age: 43·9 years) with a primary report of CLBP (>6 months) without radiculopathy were treated with a standardized approach of manual physical therapy and exercise directed at bilateral hip impairments for a total of three sessions over approximately 1 week. At initial examination, all patients completed a numeric rating pain scale (NPRS), Oswestry disability index (ODI), fear-avoidance beliefs questionnaire (FABQ), and patient-specific functional scale (PSFS). At the second and third treatment sessions, each patient completed all outcome measures as well as the Global Rating of Change (GROC).
Five of the eight (62·5%) patients reported ‘moderately better’ or higher (>+4) on the GROC at the third session, indicating a moderate improvement in self-reported symptoms. These five individuals also experienced a 24·4% reduction in ODI scores.
This case series suggests that an impairment-based approach directed at the hip joints may lead to improvements in pain, function, and disability in patients with CLBP. A neurophysiologic mechanism may be a plausible explanation regarding the clinical outcomes of this study. A larger, well-controlled trial is needed to determine the potential effectiveness of this approach with patients with CLBP.
PMCID: PMC3172945  PMID: 22547920
Chronic low back pain; Hip; Impairment; Lumbar; Manipulation; Manual therapy
16.  Clinical Perspective: How Do Clinical Test Results Differentiate Chronic and Subacute Low Back Pain Patients from “Non-Patients”? 
Our limited understanding of underlying conditions for back pain is reflected in the common use of pain-duration-based groupings. The aim of this paper was to investigate typical clinical tests used in examining low back pain (LBP) patients in order to discover how tests distinguish between chronic low back pain patients (CLBP) and subacute low back pain patients (SLBP) and if they distinguish these groups from those with no “patient status.” CLBP patients in this study were from a university hospital and SLBP patients were from five occupational health care centers. Control subjects were recruited from a university. Determination of the best predictors between CLBP and SLBP patients and between CLBP and SLBP patients and non-patients was made by a forward stepwise logistic model. A total of 157 subjects were included in the study. Of all the clinical tests, several tests in each category had high odds ratio, differentiating CLBP patients from controls. Only a few tests differentiated between CLBP and SLBP patients. The only clinical differences between SLBP patients and controls were in the mobility test and in one test of muscle tightness. The best predictor for CLBP was the lumbar spine flexion test. SLBP patients seemed to differ from the control group in lumbar flexion, in a specific anterior-posterior mobility test, and in tightness of hip flexor muscles. CLBP patients differed from SLBP patients in functional tests, in the presence of sensation in the feet, and in different pain provocation tests. Whether these tests are sufficiently sensitive to classify a more specific diagnostic or clinical subgroup remains untested, and further studies with clinical tests to differentiate among pathological conditions are necessary.
PMCID: PMC2704343  PMID: 20046561
Clinical Tests; Low Back Pain; Odds Ratios; Orthopedic Manipulative Therapy; Sensitivity; Specificity
17.  Effect of yogic colon cleansing (Laghu Sankhaprakshalana Kriya) on pain, spinal flexibility, disability and state anxiety in chronic low back pain 
International Journal of Yoga  2014;7(2):111-119.
Studies have shown that Integrated Yoga reduces pain, disability, anxiety and depression and increases spinal flexibility and quality-of-life in chronic low back pain (CLBP) patients.
The objective of this study was to compare the effect of two yoga practices namely laghu shankha prakshalana (LSP) kriya, a yogic colon cleansing technique and back pain specific asanas (Back pain special technique [BST]) on pain, disability, spinal flexibility and state anxiety in patients with CLBP.
Materials and Methods:
In this randomized control (self as control) study, 40 in-patients (25 were males, 15 were females) between 25 and 70 years (44.05 ± 13.27) with CLBP were randomly assigned to receive LSP or BST sessions. The measurements were taken immediately before and after each session of either of the practices (30 min) in the same participant. Randomization was used to decide the day of the session (3rd or 5th day after admission) to ensure random distribution of the hang over effect of the two practices. Statistical analysis was performed using the repeated measures analysis of variance.
Significant group * time interaction (P < 0.001) was observed in 11 point numerical rating scale, spinal flexibility (on Leighton type Goniometer) and (straight leg raise test in both legs), Oswestry Disability Index, State Anxiety (XI component of Spieldberger's state and trait anxiety inventory. There was significantly (P < 0.001, between groups) better reduction in LSP than BST group on all variables. No adverse effects were reported by any participant.
Clearing the bowel by yoga based colon cleansing technique (LSP) is safe and offers immediate analgesic effect with reduced disability, anxiety and improved spinal flexibility in patients with CLBP.
PMCID: PMC4097895  PMID: 25035620
Chronic low back pain; spinal flexibility; yogic colon cleansing
18.  Effect of obesity and low back pain on spinal mobility: a cross sectional study in women 
obesity is nowadays a pandemic condition. Obese subjects are commonly characterized by musculoskeletal disorders and particularly by non-specific chronic low back pain (cLBP). However, the relationship between obesity and cLBP remains to date unsupported by an objective measurement of the mechanical behaviour of the spine and its morphology in obese subjects. Such analysis may provide a deeper understanding of the relationships between function and the onset of clinical symptoms.
to objectively assess the posture and function of the spine during standing, flexion and lateral bending in obese subjects with and without cLBP and to investigate the role of obesity in cLBP.
Study design
Cross-sectional study
Patient sample
thirteen obese subjects, thirteen obese subjects with cLBP, and eleven healthy subjects were enrolled in this study.
Outcome measures
we evaluated the outcome in terms of angles at the initial standing position (START) and at maximum forward flexion (MAX). The range of motion (ROM) between START and MAX was also computed.
we studied forward flexion and lateral bending of the spine using an optoelectronic system and passive retroreflective markers applied on the trunk. A biomechanical model was developed in order to analyse kinematics and define angles of clinical interest.
obesity was characterized by a generally reduced ROM of the spine, due to a reduced mobility at both pelvic and thoracic level; a static postural adaptation with an increased anterior pelvic tilt. Obesity with cLBP is associated with an increased lumbar lordosis.
In lateral bending, obesity with cLBP is associated with a reduced ROM of the lumbar and thoracic spine, whereas obesity on its own appears to affect only the thoracic curve.
obese individuals with cLBP showed higher degree of spinal impairment when compared to those without cLBP. The observed obesity-related thoracic stiffness may characterize this sub-group of patients, even if prospective studies should be carried out to verify this hypothesis.
PMCID: PMC2821381  PMID: 20082692
19.  A Novel Tool for the Assessment of Pain: Validation in Low Back Pain 
PLoS Medicine  2009;6(4):e1000047.
Joachim Scholz and colleagues develop and validate an assessment tool that distinguishes between radicular and axial low back pain.
Adequate pain assessment is critical for evaluating the efficacy of analgesic treatment in clinical practice and during the development of new therapies. Yet the currently used scores of global pain intensity fail to reflect the diversity of pain manifestations and the complexity of underlying biological mechanisms. We have developed a tool for a standardized assessment of pain-related symptoms and signs that differentiates pain phenotypes independent of etiology.
Methods and Findings
Using a structured interview (16 questions) and a standardized bedside examination (23 tests), we prospectively assessed symptoms and signs in 130 patients with peripheral neuropathic pain caused by diabetic polyneuropathy, postherpetic neuralgia, or radicular low back pain (LBP), and in 57 patients with non-neuropathic (axial) LBP. A hierarchical cluster analysis revealed distinct association patterns of symptoms and signs (pain subtypes) that characterized six subgroups of patients with neuropathic pain and two subgroups of patients with non-neuropathic pain. Using a classification tree analysis, we identified the most discriminatory assessment items for the identification of pain subtypes. We combined these six interview questions and ten physical tests in a pain assessment tool that we named Standardized Evaluation of Pain (StEP). We validated StEP for the distinction between radicular and axial LBP in an independent group of 137 patients. StEP identified patients with radicular pain with high sensitivity (92%; 95% confidence interval [CI] 83%–97%) and specificity (97%; 95% CI 89%–100%). The diagnostic accuracy of StEP exceeded that of a dedicated screening tool for neuropathic pain and spinal magnetic resonance imaging. In addition, we were able to reproduce subtypes of radicular and axial LBP, underscoring the utility of StEP for discerning distinct constellations of symptoms and signs.
We present a novel method of identifying pain subtypes that we believe reflect underlying pain mechanisms. We demonstrate that this new approach to pain assessment helps separate radicular from axial back pain. Beyond diagnostic utility, a standardized differentiation of pain subtypes that is independent of disease etiology may offer a unique opportunity to improve targeted analgesic treatment.
Editors' Summary
Pain, although unpleasant, is essential for survival. Whenever the body is damaged, nerve cells detecting the injury send an electrical message via the spinal cord to the brain and, as a result, action is taken to prevent further damage. Usually pain is short-lived, but sometimes it continues for weeks, months, or years. Long-lasting (chronic) pain can be caused by an ongoing, often inflammatory condition (for example, arthritis) or by damage to the nervous system itself—experts call this “neuropathic” pain. Damage to the brain or spinal cord causes central neuropathic pain; damage to the nerves that convey information from distant parts of the body to the spinal cord causes peripheral neuropathic pain. One example of peripheral neuropathic pain is “radicular” low back pain (also called sciatica). This is pain that radiates from the back into the legs. By contrast, axial back pain (the most common type of low back pain) is confined to the lower back and is non-neuropathic.
Why Was This Study Done?
Chronic pain is very common—nearly 10% of American adults have frequent back pain, for example—and there are many treatments for it, including rest, regulated exercise (physical therapy), pain-killing drugs (analgesics), and surgery. However, the best treatment for any individual depends on the exact nature of their pain, so it is important to assess their pain carefully before starting treatment. This is usually done by scoring overall pain intensity, but this assessment does not reflect the characteristics of the pain (for example, whether it occurs spontaneously or in response to external stimuli) or the complex biological processes involved in pain generation. An assessment designed to take such factors into account might improve treatment outcomes and could be useful in the development of new therapies. In this study, the researchers develop and test a new, standardized tool for the assessment of chronic pain that, by examining many symptoms and signs, aims to distinguish between pain subtypes.
What Did the Researchers Do and Find?
One hundred thirty patients with several types of peripheral neuropathic pain and 57 patients with non-neuropathic (axial) low back pain completed a structured interview of 16 questions and a standardized bedside examination of 23 tests. Patients were asked, for example, to choose words that described their pain from a list provided by the researchers and to grade the intensity of particular aspects of their pain from zero (no pain) to ten (the maximum imaginable pain). Bedside tests included measurements of responses to light touch, pinprick, and vibration—chronic pain often alters responses to harmless stimuli. Using “hierarchical cluster analysis,” the researchers identified six subgroups of patients with neuropathic pain and two subgroups of patients with non-neuropathic pain based on the patterns of symptoms and signs revealed by the interviews and physical tests. They then used “classification tree analysis” to identify the six questions and ten physical tests that discriminated best between pain subtypes and combined these items into a tool for a Standardized Evaluation of Pain (StEP). Finally, the researchers asked whether StEP, which took 10–15 minutes, could identify patients with radicular back pain and discriminate them from those with axial back pain in an independent group of 137 patients with chronic low back pain. StEP, they report, accurately diagnosed these two conditions and was well accepted by the patients.
What Do These Findings Mean?
These findings indicate that a standardized assessment of pain-related signs and symptoms can provide a simple, quick diagnostic procedure that distinguishes between radicular (neuropathic) and axial (non-neuropathic) low back pain. This distinction is crucial because these types of back pain are best treated in different ways. In addition, the findings suggest that it might be possible to identify additional pain subtypes using StEP. Because these subtypes may represent conditions in which different pain mechanisms are acting, classifying patients in this way might eventually enable physicians to tailor treatments for chronic pain to the specific needs of individual patients rather than, as at present, largely guessing which of the available treatments is likely to work best.
Additional Information
Please access these Web sites via the online version of this summary at
This study is further discussed in a PLoS Medicine Perspective by Giorgio Cruccu and and Andrea Truini
The US National Institute of Neurological Disorders and Stroke provides a primer on pain in English and Spanish
In its 2006 report on the health status of the US, the National Center for Health Statistics provides a special feature on the epidemiology of pain, including back pain
The Pain Treatment Topics Web site is a resource, sponsored partly by associations and manufacturers, that provides information on all aspects of pain and its treatment for health care professionals and their patients
Medline Plus provides a brief description of pain and of back pain and links to further information on both topics (in English and Spanish)
The MedlinePlus Medical Encyclopedia also has a page on low back pain (in English and Spanish)
PMCID: PMC2661253  PMID: 19360087
20.  The Nijmegen Decision Tool for Chronic Low Back Pain. Development of a Clinical Decision Tool for Secondary or Tertiary Spine Care Specialists 
PLoS ONE  2014;9(8):e104226.
In Western Europe, low back pain has the greatest burden of all diseases. When back pain persists, different medical specialists are involved and a lack of consensus exists among these specialists for medical decision-making in Chronic Low Back Pain (CLBP).
To develop a decision tool for secondary or tertiary spine care specialists to decide which patients with CLBP should be seen by a spine surgeon or by other non-surgical medical specialists.
A Delphi study was performed to identify indicators predicting the outcome of interventions. In the preparatory stage evidence from international guidelines and literature were summarized. Eligible studies were reviews and longitudinal studies. Inclusion criteria: surgical or non-surgical interventions and persistence of complaints, CLBP-patients aged 18–65 years, reported baseline measures of predictive indicators, and one or more reported outcomes had to assess functional status, quality of life, pain intensity, employment status or a composite score. Subsequently, a three-round Delphi procedure, to reach consensus on candidate indicators, was performed among a multidisciplinary panel of 29 CLBP-professionals (>five years CLBP-experience). The pre-set threshold for general agreement was ≥70%. The final indicator set was used to develop a clinical decision tool.
A draft list with 53 candidate indicators (38 with conclusive evidence and 15 with inconclusive evidence) was included for the Delphi study. Consensus was reached to include 47 indicators. A first version of the decision tool was developed, consisting of a web-based screening questionnaire and a provisional decision algorithm.
This is the first clinical decision tool based on current scientific evidence and formal multidisciplinary consensus that helps referring the patient for consultation to a spine surgeon or a non-surgical spine care specialist. We expect that this tool considerably helps in clinical decision-making spine care, thereby improving efficient use of scarce sources and the outcomes of spinal interventions.
PMCID: PMC4136789  PMID: 25133645
21.  Large differences in cost of illness and wellbeing between patients with fibromyalgia, chronic low back pain, or ankylosing spondylitis 
Annals of the Rheumatic Diseases  2004;64(3):396-402.
Objective: To compare the cost of illness of three musculoskeletal conditions in relation to general wellbeing.
Methods: Patients with fibromyalgia, chronic low back pain (CLBP), and ankylosing spondylitis who were referred to a specialist and participated in three randomised trials completed a cost diary for the duration of the study, comprising direct medical and non-medical resource utilisation and inability to perform paid and unpaid work. Patients rated perceived wellbeing (0–100) at baseline. Univariate differences in costs between the groups were estimated by bootstrapping. Regression analyses assessed which variables, in addition to the condition, contributed to costs and wellbeing.
Results: 70 patients with fibromyalgia, 110 with chronic low back pain, and 111 with ankylosing spondylitis provided data for the cost analyses. Average annual disease related total societal costs per patient were €7813 for fibromyalgia, €8533 for CLBP, and €3205 for ankylosing spondylitis. Total costs were higher for fibromyalgia and CLBP than for ankylosing spondylitis, mainly because of cost of formal and informal care, aids and adaptations, and work days lost. Wellbeing was lower in fibromyalgia (mean, 48) and low back pain (mean, 42) than in ankylosing spondylitis (mean, 67). No variables other than diagnostic group contributed to differences in costs or wellbeing.
Conclusions: In patients under the care of a specialist, there were marked differences in costs and wellbeing between those with fibromyalgia or CLBP and those with ankylosing spondylitis. In particular, direct non-medical costs and productivity costs were higher in fibromyalgia and CLBP.
PMCID: PMC1755408  PMID: 15271773
22.  Frequency and Interrelations of Risk Factors for Chronic Low Back Pain in a Primary Care Setting 
PLoS ONE  2009;4(3):e4874.
Many risk factors have been identified for chronic low back pain (cLBP), but only one study evaluated their interrelations. We aimed to investigate the frequency of cLBP risk factors and their interrelations in patients consulting their general practitioners (GPs) for cLBP.
A cross-sectional, descriptive, national survey was performed. 3000 GPs randomly selected were asked to include at least one patient consulting for cLBP. Demographic, clinical characteristics and the presence of cLBP risk factors were recorded. The frequency of each cLBP risk factor was calculated and multiple correspondence analysis (MCA) was performed to study their interrelations.
A total of 2068 GPs (68.9%) included at least 1 patient, for 4522 questionnaires analyzed. In the whole sample of patients, the 2 risk factors most commonly observed were history of recurrent LBP (72.1%) and initial limitation of activities of daily living (66.4%). For working patients, common professional risk factors were beliefs, that LBP was due to maintaining a specific posture at work (79.0%) and frequent heavy lifting at work (65.5%). On MCA, we identified 3 risk-factor dimensions (axes) for working and nonworking patients. The main dimension for working patients involved professional risk factors and among these factors, patients' job satisfaction and job recognition largely contribute to this dimension.
Our results shed in light for the first time the interrelation and the respective contribution of several previously identified cLBP risk factors. They suggest that risk factors representing a “work-related” dimension are the most important cLBP risk factors in the working population.
PMCID: PMC2654108  PMID: 19287499
23.  Effectiveness of Chinese massage therapy (Tui Na) for chronic low back pain: study protocol for a randomized controlled trial 
Trials  2014;15(1):418.
Low back pain is a common, disabling musculoskeletal disorder in both developing and developed countries. Although often recommended, the potential efficacy of massage therapy in general, and Chinese massage (tuina) in particular, for relief of chronic low back pain (CLBP) has not been fully established due to inadequate sample sizes, low methodological quality, and subclinical dosing regimens of trials to date. Thus, the purpose of this randomized controlled trial (RCT) is to evaluate the comparative effectiveness of tuina massage therapy versus conventional analgesics for CLBP.
The present study is a single center, two-arm, open-label RCT. A total of 150 eligible CLBP patients will be randomly assigned to either a tuina treatment group or a conventional drug control group in a 1:1 ratio. Patients in the tuina group receive a 20 minutes, 4-step treatment protocol which includes both structural and relaxation massage, administered in 20 sessions over a period of 4 weeks. Patients in the conventional drug control group are instructed to take a specific daily dose of ibuprofen. The primary outcome measure is the change from baseline back pain and function, measured by Roland-Morris Disability Questionnaire, at two months. Secondary outcome measures include the visual analogue scale, Japanese orthopedic association score (JOAS), and McGill pain questionnaire.
The design and methodological rigor of this trial will allow for collection of valuable data to evaluate the efficacy of a specific tuina protocol for treating CLBP. This trial will therefore contribute to providing a solid foundation for clinical treatment of CLBP, as well as future research in massage therapy.
Trial registration
This trial was registered with of the National Institute of Health on 22 October 2013 (http://NCT01973010).
PMCID: PMC4228121  PMID: 25352050
Chronic low back pain; Effectiveness; Randomized controlled trial; Tuina; Chinese massage therapy
24.  Chronic low back pain is associated with reduced vertebral bone mineral measures in community-dwelling adults 
Chronic low back pain (CLBP) experienced in middle-age may have important implications for vertebral bone health, although this issue has not been investigated as a primary aim previously. This study investigated the associations between CLBP and dual energy X-ray absorptiometry (DXA)-derived vertebral bone mineral measures acquired from postero-anterior and lateral-projections, among community-dwelling, middle-aged adults.
Twenty-nine adults with CLBP (11 male, 18 female) and 42 adults with no history of LBP in the preceding year (17 male, 25 female) were evaluated. Self-reported demographic and clinical data were collected via questionnaires. Areal bone mineral density (aBMD) was measured in the lumbar spine by DXA. Apparent volumetric (ap.v) BMD in the lumbar spine was also calculated. Multiple linear regression models were used to examine associations between study group (CLBP and control) and vertebral DXA variables by gender, adjusting for height, mass and age.
There was no difference between groups by gender in anthropometrics or clinical characteristics. In the CLBP group, the mean (SD) duration of CLBP was 13.3 (10.4) years in males and 11.6 (9.9) years in females, with Oswestry Disability Index scores of 16.2 (8.7)% and 15.4 (9.1)%, respectively. Males with CLBP had significantly lower adjusted lateral-projection aBMD and lateral-projection ap.vBMD than controls at L3 with mean differences (standard error) of 0.09 (0.04) g/cm2 (p = 0.03) and 0.02 (0.01) g/cm3 (p = 0.04). These multivariate models accounted for 55% and 53% of the variance in lateral-projection L3 aBMD and lateral-projection L3 ap.vBMD.
CLBP in males is associated with some lumbar vertebral BMD measures, raising important questions about the mechanism and potential clinical impact of this association.
PMCID: PMC3359205  PMID: 22458361
25.  Individuals with chronic low back pain have greater difficulty in engaging in positive lifestyle behaviours than those without back pain: An assessment of health literacy 
Despite the large volume of research dedicated to understanding chronic low back pain (CLBP), patient outcomes remain modest while healthcare costs continue to rise, creating a major public health burden. Health literacy - the ability to seek, understand and utilise health information - has been identified as an important factor in the course of other chronic conditions and may be important in the aetiology of CLBP. Many of the currently available health literacy measurement tools are limited since they measure narrow aspects of health literacy. The Health Literacy Measurement Scale (HeLMS) was developed recently to measure broader elements of health literacy. The aim of this study was to measure broad elements of health literacy among individuals with CLBP and without LBP using the HeLMS.
Thirty-six community-dwelling adults with CLBP and 44 with no history of LBP responded to the HeLMS. Individuals were recruited as part of a larger community-based spinal health study in Western Australia. Scores for the eight domains of the HeLMS as well as individual item responses were compared between the groups.
HeLMS scores were similar between individuals with and without CLBP for seven of the eight health literacy domains (p > 0.05). However, compared to individuals with no history of LBP, those with CLBP had a significantly lower score in the domain 'Patient attitudes towards their health' (mean difference [95% CI]: 0.46 [0.11-0.82]) and significantly lower scores for each of the individual items within this domain (p < 0.05). Moderate effect sizes ranged from d = 0.47-0.65.
Although no differences were identified in HeLMS scores between the groups for seven of the health literacy domains, adults with CLBP reported greater difficulty in engaging in general positive health behaviours. This aspect of health literacy suggests that self-management support initiatives may benefit individuals with CLBP.
PMCID: PMC3155909  PMID: 21756363
health literacy; low back pain; health information; HeLMS; self-management

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