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.

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.

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.

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.

Efficacy of noradrenergic and serotonergic antidepressants in chronic back pain: a preliminary concentration-controlled trial.

OBJECTIVE: Although antidepressants are widely prescribed as analgesics in chronic back pain, their clinical pharmacology is not well established. Norepinephrine transporter blockade seems to be essential for analgesia, but optimal concentrations are unknown. Fixed-dose studies of serotonin reuptake inhibitors are generally negative, but such studies cannot be interpreted clearly because efficacy might be detected if concentration-response relationships were known. We evaluated (1) the feasibility of conducting a controlled-concentration study of a norepinephrine (desipramine) and a serotonin reuptake (fluoxetine) inhibitor and (2) the relationship between achieved concentrations and analgesic response. METHODS: This single-center, 12-week, double-blind, prospective, controlled-concentration study randomized 121 chronic back pain patients without major depression to active placebo (benztropine mesylate) or to predetermined low, medium, or high concentrations of desipramine (targets were 50, 110, and 150 ng/mL, respectively) or fluoxetine (targets were 100, 200, and 400 ng/mL, respectively). Of these, 83 completed the trial: 38 withdrew primarily due to side effects. RESULTS: Manipulation check revealed significant overlap of assigned and achieved concentrations related to drug intolerability. Completers' analysis of achieved concentrations revealed reduction in pain intensity was significantly greater for low-concentration desipramine (<60 ng/mL, mean Descriptor Differential Scale [DDS], 4.5) compared with placebo (DDS 6.2), higher concentrations of desipramine (>60 ng/mL, DDS 7.9), and all concentrations of fluoxetine (P < 0.05, DDS 7.1). Significant improvement in everyday function mirrored findings for pain intensity. CONCLUSIONS: Preliminary evidence for a low-concentration "therapeutic window" for noradrenergic analgesia may warrant additional study.

A placebo-controlled randomized clinical trial of nortriptyline for chronic low back pain.

To assess the efficacy of nortriptyline, a tricyclic antidepressant, as an analgesic in chronic back pain without depression, we conducted a randomized, double-blind, placebo-controlled, 8-week trial in 78 men recruited from primary care and general orthopedic settings, who had chronic low back pain (pain at T-6 or below on a daily basis for 6 months or longer). Of these 57 completed the trial; of the 21 who did not complete, four were withdrawn because of adverse effects. The intervention consisted of inert placebo or nortriptyline titrated to within the therapeutic range for treating major depression (50-150 ng/ml). The main outcome endpoints were pain (Descriptor Differential Scale), disability (Sickness Impact Profile), health-related quality of life (Quality of Well-Being Scale), mood (Beck Depression Inventory, Spielberger State Anxiety Inventory, Hamilton Anxiety/Depression Rating Scales), and physician rated outcome (Clinical Global Impression). Reduction in pain intensity scores was significantly greater for participants randomized to nortriptyline (difference in mean change 1.68, 95%-0.001, CI -3.36, P = 0.050), with a reduction of pain by 22% compared to 9% on placebo. Reduction in disability marginally favored nortriptyline (P = 0.055), but health-related quality of life, mood, and physician ratings of overall outcome did not differ significantly between treatments. Subgroup analyses of study completers supported the intent-to-treat analysis. Also, completers with radicular pain on nortriptyline (n = 5) had significantly (P < 0.05) better analgesia and overall outcome than did those on placebo (n = 6). The results suggest noradrenergic mechanisms are relevant to analgesia in back pain. This modest reduction in pain intensity suggests that physicians should carefully weigh the risks and benefits of nortriptyline in chronic back pain without depression.

One-year follow-up of first onset low back pain.

Efforts to examine the process and risk of developing chronic back pain have relied generally upon retrospective study of individuals with already established pain. In an alternative approach to understanding the clinical course and evolution of low back disorders, a cohort of 76 men experiencing their first episode of back pain was assessed prospectively at 2, 6 and 12 months following pain onset. Standard measures of pain (Descriptor Differential Scale: DDS), disability (Sickness Impact Profile: SIP), and distress (Beck Depression Inventory: BDI) were employed to classify the sample into five groups: Resolved, Pain Only, Disability/Distress Only, Pain and Mild Disability/Distress, and Clinical Range. At both 6 and 12 months post pain onset, most (78%, 72% respectively) of the sample continued to experience pain. Many also experienced marked disability at 6 months (26%) and 12 months (14%). At 12 months, no participants had worsened relative to the 2-month baseline. Doubly multivariate analyses of variance (MANOVAs) were employed to compare baseline groups (Pain Only, Pain and Mild Disability/Distress, Clinical Range) on the DDS, SIP, and BDI across time. The group by time interaction from 2 through 12 months was reliable, with greatest change occurring in the Clinical Range group in disability and distress; interestingly, the decrease in pain was comparable among all groups. Follow-up tests across measures demonstrated greater change in the early (2-6-month) interval and relative stability in the later (6-12-month) interval. Comparison of those classified as 'improvers' with those who did not improve from 2 to 12 months showed similar findings. The clinical course of first onset back pain may be prolonged for many patients, and involves a continuum of related disability and distress. Individuals at risk for marked symptoms 1 year after an initial episode of back pain can be identified early, and prompt treatment might reduce the risk of pain chronicity.

Psychosocial factors discriminate multidimensional clinical groups of chronic low back pain patients.

Previous studies have empirically defined clinical subgroups of chronic low back pain (CLBP) patients, based on differing patterns of pain, disability and emotional distress. Because these identified groups generally are comparable in terms of physical and demographic variables, variation in functional status cannot be adequately explained by medical or social factors. In the present study we evaluated whether other psychosocial factors (stress, coping attempts, and satisfaction with social supports) might differentiate the observed groups. A discriminate function analysis indicated that ratings of life adversity, coping, and social support statistically differentiate clinical groups of CLBP patients. Patients categorized as chronic pain syndrome (i.e., high levels of pain, disability and depression) reported greater life adversity, more reliance on passive/avoidant coping strategies, and less satisfaction with social support networks. Patients categorized as having good pain control (i.e., low levels of pain, disability and depression) reported less life adversity, less reliance on passive/avoidant coping strategies, and more satisfaction with social support networks. Finally, a mixed picture of less life adversity, but more reliance on passive/avoidant coping strategies and more satisfactory social support networks was reported by patients categorized in the positive adaptation to pain group (i.e., high levels of pain, but relatively low levels of disability and depression). These findings suggest that psychosocial factors may be important and complex correlates of multidimensional clinical presentations of CLBP. Psychosocial factors may also offer an avenue for intervention across 3 key dimensions of CLBP.

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.

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.

Coping activities in chronic low back pain: relationship with depression.

To help clarify the nature of coping activities in chronic pain, this study compared how depressed (n = 37) and non-depressed (n = 40) chronic low back pain (CLBP) patients attempted to cope with pain-specific and general non-pain life stressors, relative to matched healthy control subjects (n = 40). We hypothesized that depressed mood, rather than pain alone, would account for differences in coping activities between groups. Specifically, we expected that depressed CLBP patients would report a greater proportion of passive and avoidant coping responses and less active problem solving coping attempts than non-depressed patients and controls. Results indicated that depressed CLBP patients reported more passive-avoidant coping activities than did non-depressed CLBP patients and controls, whereas coping responses were similar for non-depressed CLBP patients and controls. Additionally, subjects across groups tended to report more passive-avoidant coping in response to the specific back pain stressor (i.e., exacerbation of back pain during activity) than to other life stressors. Finally, the magnitude of reported differences in coping attempts across groups varied as a function of the type of stressor (i.e., specific back pain stressor vs. general stressful life events), particularly with regard to a disinclination to seek social support in response to the back pain exacerbation. We conclude that: (1) chronic back pain patients may employ different coping activities when attempting to manage pain exacerbations than when confronting more general life stressors, and (2) an increased rate of passive-avoidant coping responses (relative to matched health controls) is associated with the combination of CLBP and concurrent depressed mood, rather than with CLBP alone.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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.

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.

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.