Patrick H. Finan

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.

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.

The role of positive affect in pain and its treatment.

Objective:This narrative review summarizes and integrates the available literature on positive affect (PA) and pain to: (1) provide a brief overview of PA and summarize the key findings that have emerged in the study of PA and pain; (2) provide a theoretical foundation from which to understand how PA operates in the context of chronic pain (CP); and (3) highlight how the prevailing psychosocial treatments for CP address PA in the therapeutic context, and offer suggestions for how future treatment development research can maximize the benefit of PA for patients with CP. Results:In experimental studies, the evidence suggests PA is analgesic. In clinical studies, the association of PA and pain is dynamic, time variant, and may be best considered in context of its interacting role with negative affect. Discussion:We offer an “upward spiral” model of PA, resilience and pain self-management, which makes specific predictions that PA will buffer maladaptive cognitive and affective responses to pain, and promote active engagement in valued goals that enhance CP self-management.

COMT moderates the relation of daily maladaptive coping and pain in fibromyalgia

&NA; Forty‐five women with fibromyalgia (FM) engaged in a 30‐day electronic diary assessment, recording daily ratings of pain and 2 forms of maladaptive coping: pain catastrophizing and pain attention. Participants were genotyped for the val158met single nucleotide polymorphism (rs4680) in the catechol‐O‐methyltransferase (COMT) gene. COMT genotype moderated the daily relations of both maladaptive coping processes and pain. FM women with the homozygous met/met genotype evidenced more pain on days when pain catastrophizing was elevated relative to heterozygous and homozygous val158 carriers. FM women with the homozygous met/met genotype evidenced more pain on days when pain attention was elevated relative to those with the homozygous val/val genotype. Evidence is presented to suggest that these are independent effects. The findings provide multimeasure and multimethod support for genetic moderation of a maladaptive coping and pain process, which has been previously characterized in a sample of postoperative shoulder pain patients. Further, the findings advance our understanding of the role of COMT in FM, suggesting that genetic variation in the val158met polymorphism may affect FM pain through pathways of pain‐related cognition. This study examined 2 forms of maladaptive coping: pain catastrophizing and pain attention. The findings provide multimeasure and multimethod support for genetic moderation of a maladaptive coping and pain process and suggest that genetic variation in the val158met polymorphism may affect fibromyalgia pain through pathways of pain‐related cognition.

Genetic influences on the dynamics of pain and affect in fibromyalgia.

OBJECTIVE The purpose of the present investigation was to determine if variation in the catechol-O-methyltransferase (COMT) and mu-opioid receptor (OPRM1) genes is associated with pain-related positive affective regulation in fibromyalgia (FM). DESIGN Forty-six female patients with FM completed an electronic diary that included daily assessments of positive affect and pain. Between- and within-person analyses were conducted with multilevel modeling. MAIN OUTCOME MEASURE Daily positive affect was the primary outcome measure. RESULTS Analyses revealed a significant gene x experience interaction for COMT, such that individuals with met/met genotype experienced a greater decline in positive affect on days when pain was elevated than did either val/met or val/val individuals. This finding supports a role for catecholamines in positive affective reactivity to FM pain. A gene x experience interaction for OPRM1 also emerged, indicating that individuals with at least one asp allele maintained greater positive affect despite elevations in daily pain than those homozygous for the asn allele. This finding may be explained by the asp alleles role in reward processing. CONCLUSIONS Together, the findings offer researchers ample reason to further investigate the contribution of the catecholamine and opioid systems, and their associated genomic variants, to the still poorly understood experience of FM.

Daily affect relations in fibromyalgia patients reveal positive affective disturbance

Objectives: To examine daily positive affective disturbance in the context of negative affect (NA) and pain among patients with fibromyalgia (FM) to determine a) if FM patients experience a deficit in daily positive affect (PA) relative to osteoarthritis (OA) patients; b) if FM patients differ from OA patients in the day-to-day relations of PA and NA; and c) if patients diagnosed with both OA and FM differ from patients with either OA-only or FM-only with respect to major outcomes. Methods: A total of 260 women with physician-diagnosed OA (n = 106), FM (n = 53), or OA/FM (n = 101) completed a 30-day electronic diary. Participants were assessed once daily on levels of PA, NA, and pain. Results: Multilevel models indicated that FM patients had less overall PA than OA patients and exhibited a stronger inverse PA-NA relation. Analyses further suggest that the OA/FM group may have been the most impaired of the three included in our study. This group was responsible for a lagged effect of PA on both affects, whereby high PA days resulted in low next-day PA and high next-day NA. Conclusion: FM patients exhibit a PA disturbance compared with OA patients. This disturbance is reflected by an overall deficit in PA and an inability to sustain PA in the face of pain and NA. Patients with both OA and FM may represent a subgroup of FM that is at particular risk for dysregulation of PA. FM = fibromyalgia; OA = osteoarthritis; PA = positive affect; NA = negative affect; DMA = Dynamic Model of Affect.

Cognitive-behavioral therapy for insomnia in knee osteoarthritis: a randomized, double-blind, active placebo-controlled clinical trial.

Insomnia is prevalent among patients with knee osteoarthritis (OA). Research indicates that sleep disruption may amplify clinical pain by altering central pain modulation, suggesting that treatment of insomnia may improve pain. The aims of this study were to evaluate the efficacy of cognitive–behavioral therapy for insomnia (CBT‐I) in patients with knee OA, to determine whether improvements in sleep predict reduced pain, and to determine whether alterations in pain modulation mediate improvements in clinical pain.

Sleep, Pain Catastrophizing, and Central Sensitization in Knee Osteoarthritis Patients with and Without Insomnia

Osteoarthritis (OA), a chronic degenerative joint disorder, is characterized by joint pain. Emerging research demonstrates that a significant number of patients evidence central sensitization (CS), a hyperexcitability in nociceptive pathways, which is known to amplify and maintain clinical pain. The clinical correlates of CS in OA, however, are poorly understood. Insomnia is prevalent in older adults with OA, and recent experiments suggest associations between poor sleep and measures of CS. Catastrophizing, a potent predictor of pain outcomes, has also been associated with CS, but few studies have investigated possible interactions between catastrophizing, sleep, and CS.

Increased sensitivity to physical activity among individuals with knee osteoarthritis: Relation to pain outcomes, psychological factors, and responses to quantitative sensory testing

Summary Sensitivity to physical activity was related to measures of central sensitization and pain catastrophizing and cross‐sectionally predicted worse pain, function, and physical performance. ABSTRACT Recent findings suggest that certain individuals with musculoskeletal pain conditions have increased sensitivity to physical activity (SPA) and respond to activities of stable intensity with increasingly severe pain. This study aimed to determine the degree to which individuals with knee osteoarthritis (OA) show heightened SPA in response to a standardized walking task and whether SPA cross‐sectionally predicts psychological factors, responses to quantitative sensory testing (QST), and different OA‐related outcomes. One hundred seven adults with chronic knee OA completed self‐report measures of pain, function, and psychological factors, underwent QST, and performed a 6‐min walk test. Participants rated their discomfort levels throughout the walking task; an index of SPA was created by subtracting first ratings from peak ratings. Repeated‐measure analysis of variance revealed that levels of discomfort significantly increased throughout the walking task. A series of hierarchical regression analyses determined that after controlling for significant covariates, psychological factors, and measures of mechanical pain sensitivity, individual variance in SPA predicted self‐report pain and function and performance on the walking task. Analyses also revealed that both pain catastrophizing and the temporal summation of mechanical pain were significant predictors of SPA and that SPA mediated the relationship between catastrophizing and self‐reported pain and physical function. The discussion addresses the potential processes contributing to SPA and the role it may play in predicting responses to different interventions for musculoskeletal pain conditions.