In vivo self-assembly of stable green fluorescent protein fusion particles and their uses in enzyme immobilization.

Bacterial inclusion bodies are aggregations of mostly inactive and misfolded proteins. However, previously the in vivo self-assembly of green fluorescent protein (GFP) fusions into fluorescent particles which displayed specific binding sites suitable for applications in bioseparation and diagnostics was demonstrated. Here, the suitability of GFP particles for enzyme immobilization was assessed. The enzymes tested were a thermostable α-amylase from Bacillus licheniformis, N-acetyl-d-neuraminic acid aldolase (NanA) from Escherichia coli, and organophosphohydrolase (OpdA) from Agrobacterium radiobacter. Respective GFP particles were isolated and could be stably maintained outside the cell. These enzyme-bearing GFP particles exhibited considerable stability across a range of temperature, pH, and storage conditions and could be recycled. The α-amylase-bearing particles retained activity after treatments at 4 to 85°C and at pHs 4 to 10, were stable for 3 months at 4°C, and could be recycled up to three times. OpdA-bearing particles retained degradation activity after treatments at 4 to 45°C and at pHs 5 to 10 and were able to be recycled up to four times. In contrast, the performance of NanA-bearing particles rapidly declined (>50% loss) after each recycling step and 3 months storage at 4°C. However, they were still able to convert N-acetylmannosamine and pyruvate to N-acetylneuraminic acid after treatment at 4 to 85°C and at pHs 4 to 11. Fluorescent GFP fusion particles represent a novel method for the immobilization and display of enzymes. Potential applications include diagnostic assays, biomass conversion, pharmaceutical production, and bioremediation.

Polyhydroyxalkanoate synthase fusions as a strategy for oriented enzyme immobilisation.

Polyhydroxyalkanoate (PHA) is a carbon storage polymer produced by certain bacteria in unbalanced nutrient conditions. The PHA forms spherical inclusions surrounded by granule associate proteins including the PHA synthase (PhaC). Recently, the intracellular formation of PHA granules with covalently attached synthase from Ralstonia eutropha has been exploited as a novel strategy for oriented enzyme immobilisation. Fusing the enzyme of interest to PHA synthase results in a bifunctional protein able to produce PHA granules and immobilise the active enzyme of choice to the granule surface. Functionalised PHA granules can be isolated from the bacterial hosts, such as Escherichia coli, and maintain enzymatic activity in a wide variety of assay conditions. This approach to oriented enzyme immobilisation has produced higher enzyme activities and product levels than non-oriented immobilisation techniques such as protein inclusion based particles. Here, enzyme immobilisation via PHA synthase fusion is reviewed in terms of the genetic designs, the choices of enzymes, the control of enzyme orientations, as well as their current and potential applications.

Residue dynamics of a contact and a systemic fungicide in pollen, nectar, and other plant matrices of courgette (Cucurbita pepo L.).

Pollen and nectar can be contaminated with a range of pesticides, including insecticides, fungicides, and herbicides. Since these matrices are important food sources for pollinators and other beneficial insects, their contamination can represent a key route of exposure. However, limited knowledge exists with respect to pesticide residue levels and their dynamics in these matrices for many crops and active ingredients (AIs). We used controlled glasshouse studies to investigate the residue dynamics of a systemic (cyprodinil) and a contact (fludioxonil) fungicide in the floral matrices and other plant parts of courgette/zucchini (Cucurbita pepo L.). We aimed to better understand the processes behind residue accumulation and decline in pollen and nectar. Each AI was applied to plants, either by spraying whole plants or by targeted spraying onto leaves only. Samples of pollen, nectar, anthers, flowers, and leaves were taken on the day of application and each subsequent morning for up to 13 days and analysed for residues using LC-MS/MS. Significant differences in residue levels and dynamics were found between AIs and floral matrices. The present study allowed for the identification of potential routes by which residues translocate between tissues and to link those to the physicochemical properties of each AI, which may facilitate the prediction of residue levels in pollen and nectar. Residues of the contact AI declined more quickly than those of the systemic AI in pollen and nectar. Our results further suggest that the risk of oral exposure for pollinators may be considerably reduced by using contact AIs during the green bud stage of plants, but application of systemic compounds could still result in a low, but continuous long-term exposure for pollinators with limited decline.

Psychiatric disorders and risk of transition to chronicity in men with first onset low back pain.

OBJECTIVE: To assess whether pre-existing psychiatric diagnoses increase the likelihood of transitioning from sub-acute to chronic back pain. DESIGN: Prospective cohort study. METHODS: Men (N = 140) experiencing a first onset of low back pain (LBP) were examined for lifetime psychiatric disorders approximately 8 weeks post pain-onset using the Diagnostic Interview Schedule (DIS-III-R), then re-evaluated at 6 months after pain onset to determine who did or did not progress to pain chronicity. OUTCOME MEASURE: Transition to chronic pain and disability was based on 6-month self-report measures of pain intensity and perceived disability. RESULTS: Men with a pre-pain lifetime diagnosis of major depressive disorder had 5 times greater risk of transitioning to chronic LBP (odds ratio [OR] = 4.99; 95% confidence interval [CI] 1.49-16.76). Increased risk was also associated with a pre-pain lifetime diagnosis of generalized anxiety (OR = 2.45; 95% CI 1.06-5.68), post-traumatic stress (OR = 3.23; 95% CI 1.11-9.44), and with current nicotine dependence (OR = 2.49; 95% CI 1.15-5.40). There were no statistically significant effects for abuse or dependence of alcohol or other psychoactive substances. DISCUSSION: Lifetime history of major depression or a major anxiety disorder may represent potential psychosocial "yellow flags" for the transition to chronicity in men with first-onset LBP. Screening for lifetime depressive or anxiety disorders may identify individuals at higher risk, who may benefit from referral for more intensive rehabilitation.

A randomized placebo-controlled trial of desipramine, cognitive behavioral therapy, and active placebo therapy for low back pain.

This clinical trial evaluated the independent and combined effects of a tricyclic antidepressant (desipramine) and cognitive behavioral therapy (CBT) for chronic back pain relative to an active placebo treatment. Participants (n = 142) were patients experiencing daily chronic back pain at an intensity of ≥4/10 who were randomized to a single-center, double-blind, 12-week, 4-arm, parallel groups controlled clinical trial of (1) low concentration desipramine titrated to reach a serum concentration level of 15 to 65 ng/mL; (2) CBT and active placebo medication (benztropine mesylate, 0.125 mg); (3) low concentration desipramine and CBT; and (4) active benztropine placebo medication. Participants completed the Differential Description Scale and Roland Morris Disability Questionnaires before and after treatment as validated measures of outcomes in back pain intensity and disability, respectively. Participants within each condition showed significant reductions from pre-treatment to post-treatment in pain intensity (mean changes ranged from = -2.58 to 3.87, Cohen's d's = 0.46-0.84) and improvements in pain disability (mean changes = -3.04 to 4.29, Cohen's d's = 0.54-0.88). However, intent-to-treat analyses at post-treatment showed no significant differences between any condition, with small effect sizes ranging from 0.06 to 0.27. The results from this clinical trial did not support the hypothesis that desipramine, CBT, or their combination would be statistically superior to an active medicine placebo for reducing chronic back pain intensity or disability. Key limitations included recruiting 71% of the planned sample size and use of multiple inclusion/exclusion criteria that may limit generalizability to broader populations of patients with chronic back pain.

Preventing progression to chronicity in first onset, subacute low back pain: an exploratory study.

OBJECTIVES: To evaluate the effects of a behavioral medicine intervention, relative to an attention control, in preventing chronic pain and disability in patients with first-onset, subacute low back pain (LBP) with limitations in work-role function. DESIGN: A 2-group, experimental design with randomization to behavioral medicine or attention control groups. SETTING: Orthopedic clinic at a Naval Medical Center. PARTICIPANTS: Sixty-seven participants with first-onset LBP of 6 to 10 weeks of duration and impairment in work function, of whom 50 completed all 4 therapy sessions and follow-up 6 months after pain onset. INTERVENTION: Four 1-hour individual treatment sessions of either behavioral medicine, focused on back function and pain education, self-management training, graded activity increases, fear reduction, and pain belief change; or attention control condition, focused on empathy, support, and reassurance. MAIN OUTCOME MEASURES: The primary outcome was proportion of participants classified as recovered, according to pre-established clinical cutoffs on standardized measures, signifying absence of chronic pain and disability at 6 months after pain onset. Secondary analyses were conducted on pain, disability, health status, and functional work category. Intervention credibility and pain belief manipulation checks were also evaluated. RESULTS: Chi square analyses comparing proportions recovered at 6 months after pain onset for behavioral medicine and attention control participants found relative rates of 52% versus 31% in the modified intent-to-treat sample (P=.09) and 54% versus 23% for those completing all 4 sessions and 6-month follow-up (P=.02). At 12 months, 79% of recovered and 68% of chronic pain participants still met criteria for their respective groups (P<.0001). Recovered participants also had higher rates of functional work status recovery at 12 months (recovered: 96% full duty and 4% light duty; chronic pain: 61% full duty, 18% light duty, and 21% medical discharge, respectively; P=.03). CONCLUSIONS: Early intervention using a behavioral medicine rehabilitation approach may enhance recovery and reduce chronic pain and disability in patients with first-onset, subacute LBP. Effects are stronger for participants attending all 4 sessions and the follow-up assessment.

Is there a therapeutic window with some antidepressants for analgesic response?

Most antidepressants and anticonvulsants used in chronic pain syndromes have dose- and concentration-response curves developed for their application to treat psychiatric disorders. Because these are important clinical tools in medication management of psychiatric syndromes, it is reasonable to expect that utilizing concentration-effect relationships and known sources of pharmacokinetic variability for determining doses for analgesia may also improve treatment tolerability and outcomes. Efforts to identify dosing "therapeutic windows" or minimum "thresholds" for analgesic efficacy have provided useful guidance for initiating treatment, reducing toxicity, and assisting with decision making in the face of limited therapeutic response. This article reviews the strengths, limitations, and potential of therapeutic drug monitoring of antidepressants and anticonvulsants as analgesics for selected chronic pain syndromes.

A review of the factors that influence pesticide residues in pollen and nectar: Future research requirements for optimising the estimation of pollinator exposure.

In recent years, the impact of Plant Protection Products (PPPs) on insect pollinator decline has stimulated significant amounts of research, as well as political and public interest. PPP residues have been found in various bee-related matrices, resulting in governmental bodies worldwide releasing guidance documents on methods for the assessment of the overall risk of PPPs to different bee species. An essential part of these risk assessments are PPP residues found in pollen and nectar, as they represent a key route of exposure. However, PPP residue values in these matrices exhibit large variations and are not available for many PPPs and crop species combinations, which results in inaccurate estimations and uncertainties in risk evaluation. Additionally, residue studies on pollen and nectar are expensive and practically challenging. An extrapolation between different cropping scenarios and PPPs is not yet justified, as the behaviour of PPPs in pollen and nectar is poorly understood. Therefore, this review aims to contribute to a better knowledge and understanding of the fate of PPP residues in pollen and nectar and to outline knowledge gaps and future research needs. The literature suggests that four primary factors, the crop type, the application method, the physicochemical properties of a compound and the environmental conditions have the greatest influence on PPP residues in pollen and nectar. However, these factors consist of many sub-factors and initial effects may be disguised by different sampling methodologies, impeding their exact characterisation. Moreover, knowledge about these factors is ambiguous and restricted to a few compounds and plant species. We propose that future research should concentrate on identifying relationships and common features amongst various PPP applications and crops, as well as an overall quantification of the described parameters; in order to enable a reliable estimation of PPP residues in pollen, nectar and other bee matrices.

Telehealth Therapy Effects of Nurses and Mental Health Professionals From 2 Randomized Controlled Trials for Chronic Back Pain.

OBJECTIVE: To compare the efficacy of mental health professional versus primary care nurse-delivered telehealth cognitive-behavioral therapy (CBT) and supportive care (SC) treatments for chronic low back pain, using data from 2 separate randomized controlled trials. Both trials were completed in the same hospital and used the same study design, research team, and outcome measures. MATERIALS AND METHODS: Participants from Study 1 (Mental Health Professional Study) (N=66; 2007 to 2011) and Study 2 (Nursing Study) (N=61; 2012 to 2016) were patients with chronic low back pain (≥4/10 intensity) randomized to either an 8-week CBT or an SC telehealth condition matched for contact frequency, format, and time. Participants completed validated measures of improvement in back pain disability (Roland Morris Disability Questionnaire [RMDQ]), pain intensity (Numeric Rating Scale [NRS]), depressive symptoms (Beck Depression Inventory 2 [BDI-2]), pain catastrophizing (Pain Catastrophizing Scale [PCS]), and overall improvement (Global Clinical Impressions [GCI]). RESULTS: Intent-to-treat analyses at posttreatment showed that scores on the RMDQ (Cohen d=0.33 to 0.55), NRS (d=0.45 to 0.90), PCS (d=0.21 to 0.41), and GCI (18.5% to 39.1%) improved significantly in both studies and in both treatments from pretreatment to posttreatment. Changes in BDI scores were inconsistent (d=-0.06 to 0.51). The analyses revealed no significant differences in treatment efficacy between the trained nurse versus the mental health professionals on the RMDQ, NRS, PCS, or GCI measures (P>0.20). DISCUSSION: Results from these clinical trials suggest that the benefits of home-based, telehealth-delivered CBT and SC treatments for chronic back pain were comparable when delivered by a primary care nurse or mental health professional.

Randomized Controlled Trial of Telephone-delivered Cognitive Behavioral Therapy Versus Supportive Care for Chronic Back Pain.

OBJECTIVE: The objective of this study was to evaluate the efficacy of a telephone-delivered, home-based cognitive-behavioral intervention for chronic low back pain in comparison to a matched supportive care (SC) treatment. METHODS: Participants (N=66) were patients with chronic back pain that were randomized to either an 8-week Cognitive-Behavioral Therapy (CBT) or a SC condition matched for contact frequency, format, and time. Participants completed validated measures of improvement in back pain disability, pain severity, and overall improvement. RESULTS: Intent-to-treat analyses at posttreatment showed that the treatment groups not show significantly different improvements in back pain disability (mean changes, -2.4 and -2.6 for CBT and SC, respectively; Cohen d, 0.49 and 0.55, respectively) or reductions in pain severity (mean changes, -0.9 and -1.4 for CBT and SC respectively; Cohen d, 0.50, and 0.90, respectively). Participants rated their overall improvement levels at 31% (CBT) versus 18.5% (SC). DISCUSSION: Results from this clinical trial suggest that home-based, telephone-delivered CBT and SC treatments did not significantly differ in their benefits for back pain severity and disability, and may warrant further research for applications to hospital settings. Major limitations included recruitment difficulties that underpowered primary analyses, the lack of objective improvement measures, and the absence of a usual care/untreated control group for comparisons.

Randomized Controlled Trial of Nurse-Delivered Cognitive-Behavioral Therapy Versus Supportive Psychotherapy Telehealth Interventions for Chronic Back Pain.

This study evaluated a nurse-delivered, telehealth intervention of cognitive-behavioral therapy (CBT) versus supportive psychotherapy for chronic back pain. Participants (N = 61) had chronic back pain (pain "daily" ≥6 months at an intensity of ≥4 of 10 scale) and were randomized to an 8-week, 12-session, CBT or to supportive care (SC) matched for frequency, format, and time, with each treatment delivered by a primary care nurse. The primary outcome was the Roland Morris Disability Questionnaire (RMDQ). Secondary outcomes included the numeric rating scale (NRS) and the Patient Global Impressions Scale (CGI). CBT participants (n = 30) showed significant improvements on the RMDQ (mean = 11.4 [SD = 5.9] vs 9.4 [SD = 6.1] at baseline and post-treatment, respectively, P < .05; d = .33), NRS (mean = 4.9 [SD = 2.1] vs 4.0 [SD = 1.9], respectively, P < .05; d = .45), and on the CGI (39.1% reporting "much improved" or "very much improved"). SC participants (n = 31) also showed significant improvements on the RMDQ (mean = 11.1 [SD = 5.4] vs 9.1 [SD = 5.2], respectively, P < .05; d = .38), the NRS, (mean = 5.0 [SD = 1.9] vs 3.8 [SD = 2.1], respectively, P < .05; d = .60), and 26.7% reporting "much improved" or "very much improved" on the CGI. Between groups comparisons of CBT and SC showed no differences on the study outcomes (Ps > .10). The results suggest that telehealth, nurse-delivered CBT, and SC treatments for chronic back pain can offer significant and relatively comparable benefits. PERSPECTIVE: This article describes the benefits of training primary care nurses to deliver evidence-based behavioral therapies for low back pain. Because of the high prevalence of chronic pain and the growing emphasis on nonopioid therapies, training nurses to provide behavior therapies could be a cost-effective way to improve pain management.

Shared and independent associations of psychosocial factors on work status among men with subacute low back pain.

OBJECTIVES: Psychosocial variables are acknowledged predictors of back disability, but multivariate studies are needed to understand their independent and overlapping effects. The objective of this prospective cohort study was to evaluate independent and shared associations of psychosocial variables on work status after first onset of low back pain (LBP) in working men. METHODS: One hundred forty male military personnel reporting subacute, first onset LBP (2 mo average duration) completed an interview-based and survey-based psychosocial assessment within the domains of job satisfaction, stress and coping, pain perceptions and beliefs, perceived functional disability, and mood disturbance. Work status was assessed at baseline, 6 and 12-month postpain onset. RESULTS: In logistic regression analyses at baseline, work status was associated with pain interference and perceptions of physical impairment. Beyond 2 months, the extent to which pain was believed to interfere with function was the only significant predictor of subsequent changes in work status. Job dissatisfaction was associated with more impaired work status, but not after controlling for income. Depressive and anxious mood symptoms were prevalent but failed to explain additional variance in work status. DISCUSSION: After first onset of men with subacute LBP, self-reported pain intensity and functional limitation account for most of the variance in work status explained by psychosocial factors; however, the resulting disability can be accompanied by mild to moderate mood symptoms. This suggests that interventions to improve function, if commenced early in the course of subacute pain, might prevent work disability.

A randomized controlled trial of gabapentin for chronic low back pain with and without a radiating component.

Gabapentin is prescribed for analgesia in chronic low back pain, yet there are no controlled trials supporting this practice. This randomized, 2-arm, 12-week, parallel group study compared gabapentin (forced titration up to 3600 mg daily) with inert placebo. The primary efficacy measure was change in pain intensity from baseline to the last week on treatment measured by the Descriptor Differential Scale; the secondary outcome was disability (Oswestry Disability Index). The intention-to-treat analysis comprised 108 randomized patients with chronic back pain (daily pain for ≥6 months) whose pain did (43%) or did not radiate into the lower extremity. Random effects regression models which did not impute missing scores were used to analyze outcome data. Pain intensity decreased significantly over time (P < 0.0001) with subjects on gabapentin or placebo, reporting reductions of about 30% from baseline, but did not differ significantly between groups (P = 0.423). The same results pertained for disability scores. In responder analyses of those who completed 12 weeks (N = 72), the proportion reporting at least 30% or 50% reduction in pain intensity, or at least "Minimal Improvement" on the Physician Clinical Global Impression of Change did not differ significantly between groups. There were no significant differences in analgesia between participants with radiating (n = 46) and nonradiating (n = 62) pain either within or between treatment arms. There was no significant correlation between gabapentin plasma concentration and pain intensity. Gabapentin appears to be ineffective for analgesia in chronic low back pain with or without a radiating component.

Depression in spouses of chronic pain patients: the role of patient pain and anger, and marital satisfaction.

Although several studies have shown that spouses of chronic pain patients may experience clinically significant depressive symptoms few studies have comprehensively examined the role of both patient and spouse-related factors in the development and maintenance of this emotional distress. Twenty-nine married male chronic benign low back pain patients and their spouses were recruited in order to examine the role of patient, spouse, and marital factors in spouse depressive symptomatology. The results indicated that 28% percent of the spouses in the sample reported significantly depressed mood. A 2-stage regression analysis was employed that revealed 3 significant predictors of spouse's depressed mood, namely patient's average pain; patient's reported levels of anger and hostility, and the spouse's level of marital satisfaction. These findings are discussed in terms of their implications for clinical interventions for pain patients and their families.

The Descriptor Differential Scale of Pain Intensity: an evaluation of item and scale properties.

Improved methods for pain measurement have both theoretical and clinical importance. This study evaluated the Descriptor Differential Scale (DDS) of Pain Intensity, a recent methodology designed for assessing pain reports in clinical samples. Experiment 1 evaluated the sensitivity of the measure to small changes in electrocutaneous stimulation relative to a traditional visual analogue scale (VAS) of pain intensity. Additionally, direct psychophysical scaling methods were employed to determine ratio-scale values for the DDS sensory items in relation to the electrocutaneous stimuli. This ratio scale was cross-validated by comparison with previously published ratio-scaled data from cross-modality matching pain intensity judgement studies. Experiment 2 evaluated the performance of the measure in both experimental and clinical pain samples, as well as the similarity of item-response patterns in each of these samples. Results indicate that the DDS of Pain Intensity is sensitive to small changes in electrocutaneous stimulation, has consistent ratio-scale properties across two different psychophysical methods, and demonstrates similar item-response patterns across divergent experimental and clinical samples. The results support the validity of the sensory DDS as a measure of pain intensity.

Weather changes and pain: perceived influence of local climate on pain complaint in chronic pain patients.

Patients with chronic pain frequently report that changes in the weather influence their pain. This study investigated differences in the perceived influence of weather on pain among 558 chronic pain patients living in 4 cities (San Diego, California; Nashville, Tennessee; Worcester, Massachusetts; and Boston, Massachusetts) in the United States. Local climatologic data for each city were obtained from the National Climatic Data Center. All patients completed a weather questionnaire, and the information they provided was compared with demographic and weather variables. The majority of all patients believed that changes in the weather affected their pain. Pain patients who were younger and who had arthritis reported the most sensitivity to changes in weather. Weather sensitivity was unrelated to all other demographic variables and to geographic region. Cold and damp conditions were considered to influence pain the most. However, the perceived effect of weather on pain was not found to be related to regional climate. Thus, the belief that pain is worsened by living in a colder climate was not supported. An equilibrium theory of weather changes and pain is discussed. Further investigations are needed to identify the mechanisms involved in the effects of weather changes on pain.

Pain and impairment beliefs in chronic low back pain: validation of the Pain and Impairment Relationship Scale (PAIRS).

Few validated instruments are available to assess beliefs and attitudes that patients have regarding pain, or ability to function despite discomfort. The Pain and Impairment Relationship Scale (PAIRS) was developed to tap these important beliefs and attitudes in chronic pain patients. Preliminary data indicate that the PAIRS is internally consistent and significantly related to impairment in a highly selected pain clinic sample of patients, including some chronic low back pain patients. The present study was designed to extend the validation of the PAIRS to a more general sample of chronic benign low back pain patients. Furthermore, additional tests supported the discriminant, convergent and divergent validity, as well as the reliability and relative independence from favorable self-report response bias of the PAIRS, by respectively demonstrating that: (1) the impairment beliefs assessed with the PAIRS were more prominent in chronic low back pain (CLBP) patients than in matched non-pain, healthy controls; (2) scores on the PAIRS were significantly related to measures of physical impairment, but not to physicians ratings of disease severity; (3) the impairment beliefs assessed with the PAIRS are readily distinguishable from cognitive distortions and emotional distress; (4) PAIRS scores for chronic low back pain patients are relatively consistent over time; and (5) PAIRS scores are not significantly associated with measures of favorable self-report response bias. We conclude that the PAIRS has demonstrated at least preliminary utility for applications by researchers and clinicians interested in chronic pain.

Prevalence, onset, and risk of psychiatric disorders in men with chronic low back pain: a controlled study.

This study used structured diagnostic interviews and DSM-III criteria to assess lifetime prevalence and pre-morbid risk of psychiatric disorder in a sample of men with long-standing chronic back pain (CLPB) attending a primary care clinic. A control group of age and demographically matched men without history of back pain was also studied. Compared to controls, men with CLBP had significantly higher lifetime rates of major depression (32% vs. 16%), alcohol use disorder (64.9% vs. 38.8%), and a major anxiety disorder (30.9% vs. 14.3%). Almost all CLBP men ever experiencing a mood disorder reported recurrent, not single, episodes. The 6 month point prevalence of major depression, but not other disorders, was also significantly elevated for men with CLBP. In CLBP, the first episode of major depression generally (58.1%) followed pain onset. While the initial major depressive episode usually commenced within the first 2 years of established pain, late onset mood disorder was also common. By comparison in most cases (81%) onset of alcohol use disorders considerably preceded pain. When an age-matching procedure was used to gauge relative vulnerability to psychiatric illness in patients and controls, CLBP patients had significantly higher pre-pain rates of alcohol use disorder but not depression. After age of pain onset, CLBP subjects had over 9 times the risk of developing major depression, but had similar rates of developing alcoholism. We conclude that (1) alcohol use disorders rather than depression may increase risk of developing CLBP, and (2) risk of new onset and recurrent major depression remains high for men throughout their pain career. This suggests that psychological adaptation to long-standing pain may be less successful than previously thought, especially with regard to recurrent mood disorder.

Depressed mood in chronic low back pain: relationship with stressful life events.

This study investigated the relationship between stressful life events and depressed mood in chronic low back pain (CLBP), using both self-report and observer-rated assessments of life happenings and depression. We hypothesized that CLBP patients with depressed mood (N = 15) would report significantly more untoward life events and ongoing life difficulties compared to CLBP patients without depressed mood (N = 17) and controls (N = 19). This prediction was confirmed. Subjects also were rated as being either in a high stress or low stress condition. Patients with depressed mood were more likely to be in the high stress condition than were either non-depressed patients or volunteers. Furthermore, the increased stress reported by the distressed group appeared to be a direct consequence of back pain-related life events, rather than from other life problems. We conclude that previously reported associations between life events and CLBP are a function of the relationship between stressful life events and depressive symptoms, which are prevalent in CLBP.

An empirical evaluation of multidimensional clinical outcome in chronic low back pain patients.

Individuals with persisting pain often present a constellation of symptoms that includes pain, health-related impairment and dysphoric mood. It is now widely accepted that comprehensive assessment must address each of these dimensions. Despite recognition of the value of multidimensional assessment, no empirical efforts have validated the construct of a multidimensional clinical outcome presentation based on the dimensions of pain, impairment and dysphoric mood. We employed cluster analytic procedures on standard measures of pain, impairment and depression in chronic low back pain (CLBP) patients (n = 96) attending a general orthopedic clinic in order to empirically characterize multidimensional clinical outcomes. Results indicated that 3 groups could be identified reliably: (1) 'Chronic Pain Syndrome' (n = 25; high levels of pain, impairment and depression), (2) 'Positive Adaptation to Pain' (n = 24; high levels of pain with low levels of impairment and depression) and (3) 'Good Pain Control' (n = 47; low levels of pain, impairment and depression). The reliability of this cluster solution was supported by several tests of internal consistency. Discriminability of the clusters was examined across both the outcome measures themselves and several additional independent variables. The cluster solution was then cross-validated in an independent sample of pain clinic CLBP patients (n = 180) to test its generalizability. Finally the stability of the cluster dimensions over time was tested by re-assessing 36 CLBP patients 6 months after they initially were characterized into 1 of the 3 outcome groups on the same measures. MANOVA results indicated that the outcome groups were differentiated statistically across assessments. The multiple outcome measures did not change significantly across time, nor did the outcome groups change differentially across time on these measures. We conclude that the outcome dimensions of pain, impairment and depression are relatively stable phenomena that differentially describe CLBP patients.