Michael T. Smith

How do sleep disturbance and chronic pain inter-relate? Insights from the longitudinal and cognitive-behavioral clinical trials literature

Sleep disturbance is perhaps one of the most prevalent complaints of patients with chronically painful conditions. Experimental studies of healthy subjects and cross-sectional research in clinical populations suggest the possibility that the relationship between sleep disturbance and pain might be reciprocal, such that pain disturbs sleep continuity/quality and poor sleep further exacerbates pain. This suggests that aggressive management of sleep disturbance may be an important treatment objective with possible benefits beyond the improvement in sleep. Little is known, however, about how to effectively treat sleep disturbance associated with pain or whether such treatment might have beneficial effects on reducing pain. A small, but growing literature has applied cognitive-behavioral therapies (CBT) for either pain management or insomnia to patients with chronic pain. In this article, we review the longitudinal literature on sleep disturbance associated with chronic pain and clinical trial literatures of cognitive-behavior therapy for pain management and insomnia secondary to chronic pain with the aim of evaluating whether the relationship between clinical pain and insomnia is reciprocal. While methodological problems are common, the literature suggests that the relationship is reciprocal and CBT treatments for pain or insomnia hold promise in reducing pain severity and improving sleep quality. Directions for future research include the use of validated measures of sleep, longitudinal studies, and larger randomized clinical trials incorporating appropriate attentional controls and longer periods of follow-up.

The association of sleep and pain: an update and a path forward.

UNLABELLED Ample evidence suggests that sleep and pain are related. However, many questions remain about the direction of causality in their association, as well as mechanisms that may account for their association. The prevailing view has generally been that they are reciprocally related. The present review critically examines the recent prospective and experimental literature (2005-present) in an attempt to update the field on emergent themes pertaining to the directionality and mechanisms of the association of sleep and pain. A key trend emerging from population-based longitudinal studies is that sleep impairments reliably predict new incidents and exacerbations of chronic pain. Microlongitudinal studies employing deep subjective and objective assessments of pain and sleep support the notion that sleep impairments are a stronger, more reliable predictor of pain than pain is of sleep impairments. Recent experimental studies suggest that sleep disturbance may impair key processes that contribute to the development and maintenance of chronic pain, including endogenous pain inhibition and joint pain. Several biopsychosocial targets for future mechanistic research on sleep and pain are discussed, including dopamine and opioid systems, positive and negative affect, and sociodemographic factors. PERSPECTIVE This critical review examines the recent prospective and experimental research (2005-present) on the association of sleep and pain in an attempt to identify trends suggestive of directionality and potential mechanisms. An update on this literature is needed to guide future clinical efforts to develop and augment treatments for chronic sleep disturbance and chronic pain.

Discordance between pain and radiographic severity in knee osteoarthritis: Findings from quantitative sensory testing of central sensitization

OBJECTIVE Radiographic measures of the pathologic changes of knee osteoarthritis (OA) have shown modest associations with clinical pain. We sought to evaluate possible differences in quantitative sensory testing (QST) results and psychosocial distress profiles between knee OA patients with discordant versus congruent clinical pain reports relative to radiographic severity measures. METHODS A total of 113 participants (66.7% women; mean ± SD age 61.05 ± 8.93 years) with knee OA participated in the study. Radiographic evidence of joint pathology was graded according to the Kellgren/Lawrence scale. Central sensitization was indexed through quantitative sensory testing, including heat and pressure-pain thresholds, tonic suprathreshold pain (cold pressor test), and repeated phasic suprathreshold mechanical and thermal pain. Subgroups were constructed by dichotomizing clinical knee pain scores (median split) and knee OA grade scores (grades 1-2 versus 3-4), resulting in 4 groups: low pain/low knee OA grade (n = 24), high pain/high knee OA grade (n = 32), low pain/high knee OA grade (n = 27), and high pain/low knee OA grade (n = 30). RESULTS Multivariate analyses revealed significantly heightened pain sensitivity in the high pain/low knee OA grade group, while the low pain/high knee OA grade group was less pain-sensitive. Group differences remained significant after adjusting for differences on psychosocial measures, as well as age, sex, and race. CONCLUSION The results suggest that central sensitization in knee OA is especially apparent among patients with reports of high levels of clinical pain in the absence of moderate-to-severe radiographic evidence of pathologic changes of knee OA.

Duration of Sleep Contributes to Next-Day Pain Report in the General Population

&NA; Cross‐sectional research in clinical samples, as well as experimental studies in healthy adults, suggests that the experiences of pain and sleep are bi‐directionally connected. However, whether sleep and pain experiences are prospectively linked to one another on a day‐to‐day basis in the general population has not previously been reported. This study utilizes data from a naturalistic, micro‐longitudinal, telephone study using a representative national sample of 971 adults. Participants underwent daily assessment of hours slept and the reported frequency of pain symptoms over the course of one week. Sleep duration on most nights (78.0%) was between 6 and 9 h, and on average, daily pain was reported with mild frequency. Results suggested that hours of reported sleep on the previous night was a highly significant predictor of the current day’s pain frequency (Z = −7.9, p < .0001, in the structural equation model); obtaining either less than 6 or more than 9 h of sleep was associated with greater next‐day pain. In addition, pain prospectively predicted sleep duration, though the magnitude of the association in this direction was somewhat less strong (Z = −3.1, p = .002, in the structural equation model). Collectively, these findings indicate that night‐to‐night changes in sleep affect pain report, illuminating the importance of considering sleep when assessing and treating pain.

Suicidal ideation, plans, and attempts in chronic pain patients: factors associated with increased risk.

Abstract This study describes suicidal behavior in a cross‐sectional sample of chronic pain patients and evaluates factors associated with increased risk for suicidal ideation. One hundred‐fifty‐three adults with nonmalignant pain (42% back pain) who were consecutively referred to a tertiary care pain center completed a Structured Clinical Interview for Suicide History, the McGill Pain Questionnaire, and the Beck Depression Inventory. Nineteen‐percent reported current passive suicidal ideation (PSI), 13% had active thoughts of committing suicide (ASI), 5% had a current suicide plan, and 5% reported a previous suicide attempt. Drug overdose was the most commonly reported plan and method of attempt (75%). Thirteen‐percent reported a family history of suicide attempt/completion. Pain‐specific and traditional suicide risk factors were evaluated as predictors of current PSI and ASI. Logistic regression analyses revealed that a family history of suicide attempts/completions was associated with a 7.5 fold increase in risk of PSI (P=0.001) and a 6.6 fold increase in ASI (P=0.003), after adjusting for significant covariates. Having abdominal pain was associated with an adjusted 5.5 fold increase in PSI (P=0.05) and a 4.2 fold increase in ASI (P=0.10). Neuropathic pain significantly reduced risk for both PSI (P=0.002) and ASI (P=0.01). Demographics, pain severity, and depression severity were not associated with suicidal ideation in multivariate analyses. These findings highlight the need for routine evaluation and monitoring of suicidal behavior in chronic pain, especially for patients with family histories of suicide, those taking potentially lethal medications, and patients with abdominal pain.

Association of catastrophizing with interleukin-6 responses to acute pain

Abstract Catastrophizing exerts its deleterious effects on pain via multiple pathways, and some researchers have reported that high levels of catastrophizing are associated with enhanced physiological reactivity to painful stimulation. In this project, 42 generally healthy adults underwent a series of psychophysical pain testing procedures assessing responses to noxious mechanical, heat, and cold stimuli. Pain catastrophizing cognitions were assessed prior to and then immediately after the various pain induction procedures. Blood samples were taken at baseline and then at several time points from the end of the procedures to 1 h post‐testing. Samples were assayed for serum levels of cortisol and interleukin‐6 (IL‐6). Both cortisol and IL‐6 increased from baseline during the post‐testing period (p’s < .05), with cortisol returning to baseline by 1 h post‐testing and IL‐6 remaining elevated. Pain catastrophizing, measured immediately after the pain procedures, was unrelated to cortisol reactivity, but was strongly related to IL‐6 reactivity (p < .01), with higher levels of catastrophizing predicting greater IL‐6 reactivity. In multivariate analyses, the relationship between catastrophizing and IL‐6 reactivity was independent of pain ratings. Collectively, these findings suggest that cognitive and emotional responses during the experience of pain can shape pro‐inflammatory immune system responses to noxious stimulation. This pathway may represent one important mechanism by which catastrophizing and other psychosocial factors shape the experience of both acute and chronic pain in a variety of settings.

Presleep cognitions in patients with insomnia secondary to chronic pain

This study had two primary objectives: (1) characterize the content of presleep cognitions of chronic pain patients and (2) evaluate the association between presleep cognitions and sleep disturbance. Thirty-one outpatients with benign chronic pain completed the Beck Depression Inventory, pain and sleep diaries and participated in an in vivo, presleep thought sampling procedure for 1 week in their homes. The three most frequently reported presleep cognitions were general pain-related thoughts (36%), thoughts about the experimental procedure (27%), and negative sleep-related thoughts (26%). Stepwise multiple regression analyses found that presleep thoughts pertaining to pain and environmental stimuli were significantly associated with sleep continuity, independent from the effects of depression and nightly pain severity. Pain severity was found to be positively associated with Wake After Sleep Onset Time. These results are consistent with cognitive-behavioral models of primary insomnia and suggest the content of presleep cognitive arousal may contribute to sleep disturbance secondary to pain.

Temporal and stagewise distribution of high frequency EEG activity in patients with primary and secondary insomnia and in good sleeper controls

In the present study, we evaluate the temporal and stagewise distribution of high frequency EEG activity (HFA) in primary and secondary insomnia. Three groups (n=9 per group) were compared: primary insomnia (PI), Insomnia secondary to major depression (MDD), and good sleeper controls (GS). Groups were matched for age, sex and body mass. Average spectral profiles were created for each sleep epoch. Grand averages were created for each NREM cycle and each stage of sleep after removing waking and movement epochs and epochs containing micro or miniarousals. It was found that HFA (in terms of relative power) tends to increase across NREM cycles, occurs maximally during stage 1 and during REM sleep, and that both these effects are exaggerated in patients with PI. In addition, HFA was found to be inversely associated with Delta activity and the three groups in our study appear to exhibit characteristic Delta/Beta patterns. Our data are consistent with the perspective that HFA is related to CNS arousal to the extent that Beta/Gamma activity occurs maximally during shallow stages of sleep and maximally in subjects with PI.

Pain-related catastrophizing as a risk factor for suicidal ideation in chronic pain

&NA; Living with chronic pain is associated with many deleterious outcomes, including a substantially increased risk of suicide. While many general risk factors for suicidal ideation and behavior have been identified, few studies have examined pain‐related factors that confer increased or decreased risk for suicidality. The present study assessed individual differences in the use of pain‐related coping strategies and pain‐related catastrophizing as correlates of suicidal ideation in patients with chronic pain. A total of 1512 patients seeking treatment for chronic pain completed a variety of questionnaires assessing pain, coping, and psychosocial functioning. On written questionnaires, approximately 32% of this clinic sample reported some form of recent suicidal ideation. The two most consistent predictors of the presence and degree of suicidal ideation were the magnitude of depressive symptoms and the degree of pain‐related catastrophizing, a maladaptive cognitive/emotional pain‐coping strategy. Demographic and other pain‐related variables such as pain severity and duration were not generally robust predictors of suicidal ideation in this sample of patients with chronic pain. These are the first findings to suggest a unique (e.g., independent of pain severity or depressive symptomatology) association between pain‐coping strategies and suicide‐related cognitions in the context of chronic pain. Further research in this area, including the addition of suicide prevention materials to pain‐coping skills training programs, may benefit large numbers of individuals who are at elevated suicide risk as a consequence of chronic pain.

The comorbidity of insomnia, chronic pain, and depression: Dopamine as a putative mechanism

Epidemiological, cross-sectional, and prospective studies suggest that insomnia, chronic pain, and depression frequently co-occur and are mutually interacting conditions. However, the mechanisms underlying these comorbid disorders have yet to be elucidated. Overlapping mechanisms in the central nervous system suggest a common neurobiological substrate(s) may underlie the development and interplay of these disorders. We propose that the mesolimbic dopamine system is an underappreciated and attractive venue for the examination of neurobiological processes involved in the interactions, development, exacerbation, and maintenance of this symptom complex. In the present article, studies from multiple disciplines are reviewed to highlight the role of altered dopaminergic function in the promotion of arousal, pain sensitivity, and mood disturbance. We argue that studies aiming to elucidate common factors accounting for the comorbidity of insomnia, chronic pain, and depression should evaluate functioning within the mesolimbic dopaminergic system and its effect on common processes known to be dysregulated in all three disorders.