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. Author manuscript; available in PMC: 2022 Nov 1.
Published in final edited form as: Health Psychol. 2021 Nov;40(11):793–802. doi: 10.1037/hea0001144

Pediatric Sickle Cell Pain-Sleep Relationships: The Roles of Positive and Negative Affect

Cecelia Valrie 1,2, Kristen Alston 3, Krystal Morgan 4, Rebecca Kilpatrick 5, India Sisler 6, Beng Fuh 7
PMCID: PMC9260698  NIHMSID: NIHMS1818648  PMID: 34914484

Abstract

Objective:

The current study investigated the role of affect in the daily sleep quality-pain severity relationship in youth with sickle cell disease (SCD). Previous investigations have not allowed researchers to examine whether positive and negative affect work differentially in their relations with pediatric SCD pain, sleep, and the sleep-pain relationship. The current study focused on examining the possible mediating and moderating roles positive and negative affect have in the sleep-pain relationship for youth with SCD.

Methods:

Eighty-eight youth with SCD (aged 8-17 years), and their guardians were recruited from three regional pediatric SCD clinics. Youth completed a twice daily ecological momentary assessment, where they reported on their daily pain severity, sleep quality, positive affect and negative affect. Multilevel models were calculated to examine the relationship between negative affect, positive affect, and the sleep-pain relationship.

Results:

Multilevel mediation analyses indicated that low positive affect mediated the daily cyclic relationships between poor sleep and high pain. Moderation analyses indicated that high negative affect strengthened the relationship between high pain severity and poor sleep quality that night.

Conclusion:

Further research is needed to examine the differential roles of positive and negative affect in other pain and adult SCD populations. Research examining the mechanisms by which positive and negative affect may influence the sleep-pain relationship is needed to inform future interventions to improve sleep and pain in the pediatric SCD population.

Keywords: sickle cell disease, pain, sleep, affect

INTRODUCTION

For youth with sickle cell disease (SCD), a genetic disorder of red blood cells seen primarily in people of African descent, persistent pain is a common disease complication and often results in recurrent pain episodes lasting an average of 2 to 3 days (Rees et al., 2010). In addition, these recurrent pain episodes may predispose youth with SCD to developing chronic pain in late adolescence or young adulthood. A common comorbidity with pain in youth with SCD is sleep problems, which is consistent with research in other pediatric and adult pain populations (Allen et al., 2016; Babiloni et al., 2019; Haack et al., 2020; Valrie et al., 2013). Micro-longitudinal research has indicated that the sleep-pain relationship in youth with SCD is cyclic (Fisher et al., 2018; Valrie et al., 2007a; Valrie et al., 2019). Specifically, poor sleep quality has been associated with high pain severity the next day, and high pain severity during the day has been associated with poor sleep quality that night. Also, both high pain and poor sleep quality have been related to worse functional outcomes in pediatric and adult pain populations (Evans et al., 2017; Theadom, et al., 2007; Turk et al., 2016; Valrie et al., 2013).

To develop effective interventions to reduce pain and improve sleep in youth with SCD, it is essential to identify key mechanisms connecting daily pain and sleep experiences. Based on a systematic review, Valrie and colleagues (Valrie et al., 2013) proposed a Model of the Pain-Sleep Relationship in Pediatric Persistent Pain Populations. This model posits that, beyond disease specific factors, affect plays a key role in understanding the sleep-pain relationship. Of note, sleep-pain-affect relationships in youth with SCD may be different than what is noted in other pain populations due to differences in pain presentation and possible racial differences. For example, pediatric SCD pain often presents as acute, severe, recurrent pain episodes (Dampier et al., 2002; Rees et al., 2010; Uwaezuoke et al., 2018) in contrast to other pediatric pain populations, such as juvenile rheumatoid arthritis, which generally present as continuous daily pain (Anthony & Schanberg, 2003; Rashid et al., 2018). Also, research findings from the adolescent and adult literature indicates coping differences between Black and White individuals, which may extend to how they affectively respond to pain and poor sleep (Meints et al., 2016; Mullis & Chapman, 2000; Vassillière et al., 2016). Thus, the aim of the current study was to further test and refine the applicability of the Pain-Sleep model for youth with SCD by examining what roles (i.e., mediational or moderational) positive and negative affect might play in the sleep-pain relationship for this population.

Negative affect has been related to higher pain intensity and worse pain-related outcomes, while positive affect has been related to reduced pain and appears to buffer the impact of pain on functioning and other health outcomes (Hanssen et al., 2017). Proposed pathways linking negative affect to pain include increased pain-related fear and increased inflammation, a key biological trigger linked to the development and exacerbation of pain. While positive affect is believed to broaden attention, cognition, and behavioral flexibility, which counters fear-avoidance, as well as reducing cortisol and inflammation. Affect has also been strongly linked to poor sleep, with a literature base supporting the connection between poor sleep, negative mood and psychiatric mood disorders (Brown et al., 2018; Fang et al., 2019). Though more limited, there is also research linking good quality sleep to high positive affect (Ong et al., 2016), including in adults with chronic pain (Song et al., 2015). These findings support the hypothesis that poor sleep could lead to high negative affect and low positive affect, which would lead to higher pain intensity. However, high negative affect and low positive affect may also alter the ability for individuals to cope with poor sleep and thus, strengthen the relationship between poor sleep and high pain in certain populations.

There is limited research examining positive and negative affect as potential mediators or moderators of the sleep-pain relationship. A systematic review of mediation studies exploring the sleep-pain relationship in pediatric and adult populations found nine articles, with two examining both positive and negative affect, and four examining negative affect/internalizing symptoms only (Whibley et al., 2019). Findings indicated that there was evidence that negative affect/internalizing symptoms mediate the relations between poor sleep and pain; but that the evidence was limited given that all of the identified studies were cross-sectional. To date, only four published studies have investigated both positive and negative affect as mediating factors for the sleep-pain relationship in non-SCD samples (Arnison et al., 2021; Evans et al., 2017; Finan et al., 2017; Ravyts et al., 2018). Two studies used pediatric samples and both indicated that negative affect, but not positive affect, mediate the sleep-pain relationship. Specifically, results from a longitudinal study of 7th and 8th graders followed across 5-years indicated that negative affect – depressed and anxious mood – mediated the relationship between poor sleep and subsequent pain, but not pain and subsequent sleep (Arnison et al., 2021). A cross-sectional study of 213 youth with chronic pain indicated that high negative affect mediated the relationship between poor sleep and high pain (Evans et al., 2017). Of note, the pediatric findings were inconsistent with findings from the two adult studies that support positive affect a mediator of the sleep-pain relationship. Findings from a cross-sectional study of 948 adults with chronic pain indicated positive and negative affect mediate the relationship between sleep disturbance and pain interference ( Ravyts et al., 2018). An experimental study of 45 healthy adults found disrupting sleep for one-night lead to less inhibition of pain through decreases in positive affect, but not negative affect (Finan et al., 2017).

As for moderation, three studies have investigated whether positive and negative affect influence the relationship between pain and sleep in non-SCD samples. Results from a study of youth with chronic pain (Evans et al., 2017) indicated that positive or negative affect did not moderate the association between sleep and pain. These findings are consistent with a cross-sectional study of adults with chronic back and knee pain (Thong et al., 2016) that found that positive affect did not moderate the association between sleep and pain severity; the study did not examine whether negative affect moderated the associations. However, findings from the only longitudinal study, a daily diary study of 22 adult women with chronic pain (O’Brien et al., 2011), indicated that baseline levels of depression moderate the association between sleep quality and pain. Specifically, women with higher levels of baseline depression had a stronger bi-directional relationship between poor sleep quality and high pain. The study did not examine positive affect as a possible moderator.

To date, only two studies of individuals with SCD have examined the role of affect in the context of the sleep-pain relationship, and both have used pediatric populations. A study of 20 children with SCD (Valrie et al., 2008) using daily paper and pencil diaries found that poorer affect mediated the cyclic relationship between poor sleep quality and high pain severity, and that the relationship between poor sleep and high pain the next day was strengthened at increasing levels of poor affect. However, the population was limited to youth aged 8 to 12 years of age, the use of paper and pencil diaries may have introduced recall bias, and the study did not distinguish between positive affect and negative affect. A cross-sectional study of 96 pediatric hematology/oncology patients, which included 48 youth with SCD (Baker et al., 2017) found that more internalizing symptoms mediated the relationship between more symptoms of sleep disordered breathing and high pain frequency. Limitations of the study included that is was cross-sectional, used care-giver report of internalizing symptoms, and focused exclusively on negative affect.

Overall, there is research indicating that affect plays a significant role in the relationship between sleep and pain in pediatric populations, such as youth with SCD. However, that research is sparse, primarily cross-sectional, and often does not distinguish between positive and negative affect. Thus, previous investigations have not allowed for researchers to examine whether positive and negative affect work differentially in their relations with pediatric SCD pain, sleep, and the sleep-pain relationship. To address the limitations of previous studies, a micro-longitudinal design was employed using ecological momentary assessments (EMAs) to investigate whether positive and negative affect mediates or moderates the cyclic relationship between poor sleep and high pain in youth with SCD. Previous investigations using EMA data (Fisher et al., 2018; Valrie et al., 2019) found a cyclic relationship between daily reports of sleep quality (i.e., subjective sleep quality and sleep efficiency) and pain severity, but not between sleep duration and pain severity. Specifically, poor subjective sleep quality and worse sleep efficiency at night predicted high pain severity the next day, and that high pain severity during the day predicted poor subjective sleep quality and worse sleep efficiency that night. Thus, the current study is focused on understanding the role of affect in the daily sleep quality-pain severity relationship in youth with SCD. It was hypothesized that high negative affect (but not positive affect) would mediate the daily cyclic relationship between poor sleep quality and high pain severity. It was also hypothesized that positive affect would weaken and negative affect would strengthen the cyclic relationship between poor sleep quality and high pain severity.

METHODS

Participants

Youth with SCD and their guardians were recruited from three regional pediatric SCD clinics in the southeastern US as part of a larger study of sleep, pain and related factors in youth with SCD. A detailed description of recruitment and assessment procedures for the primary study can be found in our previously published paper (Valrie et al., 2019). That paper focused on identifying which aspects of sleep were related to variations in daily SCD pain in youth with SCD, and whether the relationships between sleep and SCD pain was influenced by age. Findings indicated that poor self-reported daily sleep quality was predictive of high pain severity the next day, and as age increased, the relationship between poor continuous sleep problems, but not daily sleep quality, and high daily pain severity was strengthened. The current study is an extension of that work investigating the roles positive and negative affect play in the daily pain-sleep relationship determined in the previous paper. To be eligible for the larger study, youth were required to have a diagnosis of SCD, be aged 8 to 17 years, English speaking, and to have had a SCD pain episode in the past year, which is defined as at least 20 minutes of SCD pain (Gil et al., 1991). To be eligible for the current study, youth had to have at least 2 weeks (24 entries) of a possible 4 weeks (48 entries) of daily EMA data. Exclusion criteria included having a comorbid pain condition, neurological impairment that would impede completion of the measures, history of extreme noncompliance as indicated by a health care provider, being on chronic blood transfusions, or currently receiving a sleep intervention. Of the 123 youth-guardian pairs in the larger study, 88 met the additional criteria of 2 weeks of EMA (72% of the larger sample). The final sample of youth did not significantly differ from the larger sample based on age, sex, race, SCD genotype severity, or whether they are currently prescribed hydroxyurea – the only FDA approved SCD modifying drug at the time the data was collected.

Procedures

Recruitment and data collection began in 2011 and ended in 2015. Potential youth participants and their guardians were approached at the youth’s regularly scheduled clinic visit. If they were eligible and interested in participating, guardians completed written consent documents and youth completed written assent documents. Once the consent process was complete, the youth-guardian pairs completed measures, including demographic and disease information forms. Medical chart reviews were conducted to confirm disease information. Youth were then asked to complete an EMA twice a day, in the morning and evening for up to 4 weeks. The EMA consisted of brief surveys delivered via an app on either an Apple or Android device. Youth without a mobile device were loaned an Apple device for the study. In the morning, youth reported on their sleep the night before (e.g., subjective sleep quality) and in the evening, they reported on their pain, negative affect, and positive affect during the day. Pain the previous night was also reported in the morning EMA, but it was not used in the current analyses as we wanted to have some temporal separation between sleep and pain reports, and thus, decided to focus exclusively on daily pain ratings. Parents did not have a formal role in establishing compliance, but would often reported monitoring the youth’s EMA compliance. To promote adherence, an alarm was programmed on each device to sound every morning and evening at times selected by the youth with consultation from their guardian. The youth were also contacted once a week by study staff via phone and mail to provide feedback on compliance, and problem solve any technical or other issues that may have arisen. Youth participants were compensated with a $5 gift cards for each week (7 days) of e-diaries completed. Age was not related to number of diaries completed (r = −.03, p = .76). The research was approved and monitored by the institutional review boards at Virginia Commonwealth University, East Carolina University, and the University of North Carolina at Chapel Hill.

Measures

Demographic and Disease Information.

Guardians reported on the youth’s age, sex, race, and SCD genotype. Medical charts were then reviewed to confirm SCD genotype, and determine if the youth were currently prescribed hydroxyurea. For the primary analyses, SCD genotype was dichotomized as severe genotypes (i.e., HbSS and HbSβ0 = 1) and moderate (e.g., HbSC, HbSβ+, and other = 0).

EMA: Sleep Quality.

During the morning EMA, youth were asked to rate their sleep quality on a 100 mm VAS scale ranging from “did not sleep well” (0 mm) to “slept very well” (100 mm) and with instructions to “move the marker on the line to show how well you slept last night.” Previous research has provided strong support for the reliability and validity of daily reports to assess sleep (Wolfson et al., 2003), including youth-completed daily reports (Gaina et al., 2004; Sadeh et al., 2000).

EMA: Pain.

During the evening EMA, youth were asked if they experienced any SCD pain that day. If they indicated no, they were automatically given a pain severity score of 0. If they indicated yes, they were asked to rate their average pain severity for that day on a 100 mm horizontal visual analog scale (VAS) ranging from “not hurting at all” (0 mm) to “hurting a whole lot” (100 mm). The VAS has been found to be reliable and valid for assessing daily SCD pain in youth with SCD (Gil et al., 2003; Valrie et al., 2007b).

EMA: Positive and Negative Affect.

During the evening EMA, youth completed 10 items from the Positive and Negative Affect Schedule for Children (PANAS-C; Laurent et al., 1999). The PANAS-C is a 20-item self-report measure that assesses levels of positive and negative affect. Consistent with previous EMA studies of youth (Connelly et al., 2012; Connelly et al., 2017; Forbes et al., 2012), the subset of 10 items chosen included five assessing negative affect and five assessing positive affect. Youth were asked to rate how much of each emotion they were feeling today using a scale ranging from 1 (very slightly or not at all) to 5 (extremely), and the five items in each area were then summed to produce a number between 5 and 25. For the negative affect scale, the within-person Chronbach alpha mean was 0.83 (Range = 0.69 to 0.88), and for the positive affect scale was 0.79 (Range = 0.61 to 0.86) for the study sample.

Statistical Analyses

Descriptive and moderation analyses were conducted using Version 9.4 of the SAS System for Windows (SAS/STAT, 2013). SAS Proc Mixed was used to calculate the moderation models. Mediation analyses were conducted using the MLmed macro, version 2 (Hayes & Rockwood, 2020; Rockwood, 2017) in SPSS, Version 26. To examine the relationships between negative affect, positive affect, and the sleep-pain relationship, multilevel models (MLMs) were calculated. The MLMs used restricted maximum likelihood estimation, unstructured between-person error structures, and continuous-time autoregressive within-person error structures. Final models included a random intercept and the lagged effect of the outcome at level 1; and age, sex, SCD genotype, and whether the youth were currently taking hydroxyurea were included as level 2 covariates. To decrease collinearity, all of the EMA variables (i.e., sleep, pain, negative affect, and positive affect) were person-mean centered. Youth completed a mean of 81.87% of the possible EMA entries, resulting in a mean of 51 EMA entries per youth (approximately 25 morning entries and 25 evening entries each), which is equivalent to 3.64 weeks per youth participant (Valrie et al., 2019). Missing data was handled using full information maximum likelihood in the MLM analyses (Enders, 2010). Specific models are detailed below.

To investigate whether negative and positive affect mediated the pain-sleep relationship, within-person effects of the model were estimated, and Monte Carlo estimation was used to estimate indirect effects. The within-person variability was represented by the person’s daily report. The following parameters for a 1-1-1 mediation model were estimated: fixed and random intercepts, fixed effects, and the random effect between mediators and outcomes. Models were calculated predicting pain and sleep quality separately, with both positive and negative affect included as potential mediators in the same model.

To investigate whether negative or positive affect moderated the pain-sleep relationship, MLMs were calculated with negative affect, positive affect, and the interactions between the affect variables and the predictor variables (e.g., subjective sleep quality in the model predicting next day pain severity, and pain severity in the model predicting subjective sleep quality that night) as level 1 variables. Interactions were created by multiplying the affect variables with the predictor variables. Significant interactions were probed using Preacher, Curran, and Bauer (Preacher et al., 2006) online interactive calculator for probing interactions. The calculator was used to calculate simple intercepts and slopes for the predictors variables at varying levels of age (i.e., mean and ±1 SD of the mean), and to test whether the simple intercepts and slopes were significantly different from 0.

RESULTS

Sample demographics are reported in Table 1. On average, youth participants were 11.66 years (SD = 2.99), female (59%), Black/African American (97.73%), had a severe SCD genotype (53%), and were currently prescribed hydroxyurea (54%).

Table 1.

Demographic and Disease Data (N = 88)

N % N
Female 52 59.10% 88
Black/African AmericanGenotype 86 97.73% 88
Genotype
 HBSS 44 50% 88
 HBSC 27 31% 88
 HbSβ+ 12 14% 88
 HbSβ0 3 3% 88
 Other 2 2% 88
Hydroxyurea 47 54% 88
Mean SD Range
Age (years) 11.66 2.99 8 - 17
EMA Data
 % of Pain Days 22.40% 26.70% 0% - 100%
 Pain Severity 13.50 18.82 0 - 88.39
 Sleep Quality 74.66 16.59 22.07 - 99.94
 Negative Affect 7.69 2.62 5.04 - 18.10
 Positive Affect 17.11 4.13 8.33 - 25.00
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Note: EMA = Ecological momentary data, and EMA data presented is based on person-centered means.

Affect Mediating Sleep-Pain Relationships

Results for the mediation analyses are presented in Figure 1. The mediation analyses predicting daily pain severity indicate that taking into account positive and negative affect, low nightly sleep quality was directly related to high next day pain severity (b = −.13 [ −.18;−.09 ], p < .001) and indirectly related to high next day pain severity through positive affect (b = −.02 [−.03; −.01], p < .001). Specifically, low sleep quality was related to low next day positive affect, and low daily positive affect was related to high daily pain severity. The mediation analyses predicting daily sleep quality indicated that taking into account positive and negative affect, high pain severity during the day was directly related to low sleep quality that night (b = −.06 [ −.11;−.01 ], p = .018) and indirectly related to low nightly sleep quality through positive affect (b = −.01 [−.03; −.00], p = .020). Specifically, high pain severity during the day was related to low positive affect that day, and low positive affect during the day was related to low sleep quality that night.

Figure 1. Multilevel Analyses for Positive and Negative Affect Mediating the Sleep-Pain Relationships.

Figure 1

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Note. Parameters are unstandardized regression coefficients. The box summarizes the estimated mediation effects. Models controlled for age, sex, hydroxyurea use, and lagged effects of outcome (e.g., pain day before for top model and sleep quality the night before for bottom model).

*p < .05, **p < .01, ***p<.001.

Affect Moderating Sleep-Pain Relationships

The results of the multilevel moderation analyses are shown in Tables 2 and 3. Results from the model predicting next day pain severity indicated that the previous day’s pain severity ( t = 5.46, p < .001), subjective sleep quality (t = −3.61, p < .001) and positive affect (t = −5.28, p < .001) uniquely predicted pain severity. Results from the model predicting sleep quality found that the previous night’s sleep quality (t = −3.34), positive affect (t = 2.00, p < .05), and the interaction between pain severity and negative affect (t = −3.50, p <.001) uniquely predicted sleep quality. Probing of the interaction indicated that high daily pain only predicted poor sleep quality that night when negative affect was high, and not when negative affect was low or medium. Overall, the pattern of findings indicated that as negative affect increased, the relationship between high pain severity and poor sleep that night became stronger (see Figure 2).

Table 2.

Negative and Positive Affect Moderating the Model Using Sleep to Predict Next-Day Pain (N = 1795)

Beta SE t value
Previous Day Pain Severity 0.14 0.3 5.46***
Sleep Quality −0.09 0.03 −3.61***
Positive Affect −0.89 0.17 −5.28***
Negative Affect −0.10 0.21 −0.46
SQ * PA 0.01 0.01 1.51
SQ * NA 0.01 0.01 1.56
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Note: Controlled for Age, Sex, SCD Genotype, and Hydroxyurea; SQ = sleep quality, PA = positive affect, NA = negative affect.

*

p < .05

**

p < .01

***

p<.001.

Table 3.

Negative and Positive Affect Moderating the Model Using Pain to Predict Next-Day Sleep (N = 1512)

Beta SE t value
Previous Night Sleep Quality −0.09 0.03 −3.34***
Pain Severity −0.04 0.03 −1.50
Positive Affect 0.35 0.18 2.00*
Negative Affect −0.13 0.22 −0.60
PS * PA 0.01 0.01 0.83
PS * NA −0.03 0.01 −3.50***
Simple Slope P-value
Low NA −0.01 .69
Medium NA −0.04 .13
High NA −0.07 .015*
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Note: Controlled for Age, Sex, SCD Genotype, and Hydroxyurea; PS = pain severity, PA = positive affect, NA = negative affect.

*

p < .05

**

p < .01

***

p<.001.

Figure 2. Simple Slope Equations of Daily Pain Severity on Nightly Sleep Quality at Conditional Levels of Negative Affect.

Figure 2

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Note. NA = negative affect.

Negative-Affect Only Models

Positive and negative affect were negatively correlated (r = −.31, p < .01). This raises the possibility that the null findings concerning negative affect are because positive and negative affect are functioning on a common affective pathway that happens to be more strongly explained by positive affect. To investigate this possibility, we calculated the multilevel models with negative affect, excluding positive affect. Findings from these models were fairly consistent with the models including both positive and negative affect. The exception was that negative affect was related to sleep that night (b = −.46 [ −.84;−.07 ], p = .02). However, negative affect did not mediate the bi-directional links between pain and sleep, and did not moderate the link between sleep and next-day pain.

DISCUSSION

The aim of the current study was to use a micro-longitudinal design employing EMA to investigate whether positive and negative affect mediates and/or moderates the cyclic relationship between poor subjective sleep quality and high daily pain severity in youth with SCD. As detailed in our previous publication (Valrie et al., 2019), the sample was consistent with other pediatric diary studies that report that the majority of youth with SCD report frequent low-level SCD pain episodes and good quality sleep; but also report high variability in sleep and pain experiences both between youth and across days (Dampier et al., 2002; Fisher et al., 2018; Shapiro et al., 1995; Valrie et al., 2008).

The current study extends previous studies examining the sleep-pain relationship in with other populations (Arnison et al., 2021; Baker et al., 2017; Evans et al., 2017; Finan et al., 2017; O’Brien et al., 2011; Ravyts et al., 2018; Thong et al., 2016), which have been primarily cross-sectional, and a previous longitudinal study of youth with SCD that failed to separately examine positive and negative affect (Valrie et al., 2008). Findings from the current study indicated that low positive affect mediates the cyclic relationship between poor sleep and high pain severity, while negative affect does not. These findings are inconsistent with our hypothesis and the two previous studies of non-SCD pediatric populations, which indicated that negative affect, but not positive affect, mediates the sleep-pain relationship (Arnison et al., 2021; Evans et al., 2017). Of note, one study was cross-sectional (Evans et al., 2017); thus, not allowing for a rigorous test of mediation. The other study was a 5-year longitudinal study using a non-pain sample (Arnison et al., 2021). Positive and negative affect may function differently for youth who experience less frequently pain, which would be expected in a non-pain sample, and when these relations are being examined over years versus on a daily basis. Both of these hypotheses would need to be tested empirically. Of note, our findings are consistent with results from two adult studies, including the only study to experimentally manipulate sleep patterns, which indicated that positive affect mediates the sleep-pain relationship (Finan et al., 2017; Ravyts et al., 2018). Thus, our findings are consistent with the most rigorous investigation of the daily sleep-pain relationship.

It was also hypothesized that positive and negative affect moderated the cyclic pain-sleep relationship in youth with SCD. The hypothesis was partially supported in that, findings indicated high negative affect is associated with a stronger relationship between high pain severity during the day and poor subjective sleep quality that night, and that positive affect does not moderate the bi-directional sleep-pain relationships. The findings concerning positive affect are consistent with previous studies (Evans et al., 2017; Thong et al., 2016). However, the findings concerning negative affect are inconsistent with a previous cross-sectional study of youth with chronic pain (Evans et al., 2017). Our findings are consistent with a daily diary study of 22 adult women with chronic pain that indicated baseline depression symptoms strengthen the daily bi-directional relationship between poor sleep and high pain (O’Brien et al., 2011). Also, findings from a previous daily diary study of school-age SCD patients indicated affect, which was not divided into negative and positive affect, moderates the bi-directional sleep-pain relationship (Valrie et al., 2008).

Beyond the methodological differences noted above, the inconsistencies between our findings and the three previous studies using non-SCD pediatric samples are possibly due to racial differences in how youth emotionally respond to stressors, such as pain and poor sleep. The samples used in the previous studies were primarily Non-Hispanic White, while the majority of our sample was Black. Results from a study (Carter & Kirkinis, 2020) indicated that Black and White adults differentially respond to race-based stress, such that Black individuals tend to respond with a wider range of emotional and physiological responses. However, there is a lack of information on if there are racial differences in patterns of positive and negative affect reactions to stress. Overall, there is a need to explore whether these findings hold for adults with SCD and other Black individuals who frequently experience pain, as well as to examine for possible racial differences in patterns of positive and negative affect responses to pain, sleep, and other types of stressors.

Limitations of the current study may have impacted the findings. Specifically, because of the design of the EMA, affect and pain severity data was collected at the same time every day. This may have inflated the relationships between positive affect, negative affect, and pain severity. Despite this issue, positive and negative affect still appeared to have differential relationships with the sleep-pain relationship. Another limitation is that the current study focused exclusively on subjective sleep quality, and findings may differ when examining other aspects of sleep, such as sleep duration and objective indicators of sleep quality as measured via polysomnography and actigraphy. The decision to focus on subjective sleep quality was made due to previous research consistently relating worse sleep quality, but not sleep duration, to daily pain severity in youth with SCD (Fisher et al., 2018; Valrie et al., 2019), which is essential for testing for mediation. Notably, an EMA study with accompanying actigraphy found worse sleep efficiency (an indicator of sleep quality) to be related to daily SCD pain severity in youth (Fisher et al., 2018). Future research should examine whether positive and negative affect influence the relations between sleep efficiency and daily pain severity.

Another limitation is that the current study focused on low levels of negative affect over a relatively short period of time (1 month). The relationships examined may be different if examining higher levels of negative affect, such as symptoms of anxiety and depression, over the course of years. Findings from a 3-year longitudinal study of young adults with chronic pain (Bonvanie et al., 2016) and a 5-year longitudinal study of 7th and 8th graders (Arnison et al., 2021) indicate that anxiety and depression symptoms mediate the relationship between sleep problems and pain. The relationships may also be different after years of continuously escalating sleep and pain problems. Findings from our previous publication (Valrie et al., 2019) indicate that as youth age, the relationship between continuous sleep problems, not daily sleep problems, and daily pain increase. Thus, though we do not expect the daily pain-sleep-affect relationships to change, cumulative sleep problems may result in higher overall levels of negative affect that may result in long-term increases in pain. Overall, research is needed to investigate the role of anxiety and depression symptoms, as well as how the roles of positive and negative affect in the sleep-pain relationship may change over long periods of time and in the face of accumulating sleep and pain problems. Lastly, the current study only examined affective valence (e.g., negative or positive), but other aspects of affect may be important for understanding the sleep-pain relationship. For example, affective activation or arousal has been related to health. An example of a high arousal positive affect is excitement and a low arousal positive affect is contentment. Findings from a study of 186 women with early stage breast cancer indicated that the relationships between positive affect and levels of inflammatory biomarkers were different based on level of arousal of the affect (Moreno et al., 2016).

Despite the limitations, the current study’s findings highlight areas for future research and clinical implications. These findings support the Dynamic Model of Affect (Davis et al., 2004), which indicates that positive and negative affect should be investigated separately. These findings also support the applicability of the Model of the Pain-Sleep Relationship in Pediatric Persistent Pain Populations (Valrie et al., 2013), but highlight the need to tailor the model to be specific to different pain populations, particularly as researchers investigate the roles that positive and negative affect may play. Specifically, the findings emphasize the need to focus on positive affect, as well as negative affect, when examining and addressing pain and sleep in youth with SCD. However, there is a need to further validate these findings with other pain populations and with adults with SCD. As individuals with SCD age, research indicates their pain patterns transition from acute, discrete pain episodes to chronic (continuous) pain (Brandow et al., 2017). Although research in adults with SCD also support a relationship between pain and sleep (Gileles-Hillel et al., 2015; Moscou-Jackson et al., 2015), the roles that positive and negative affect may plan in this relationship may be different given the differences in pain patterns.

Research is also needed to investigate possible mechanisms for how positive and negative affect influence the sleep-pain relationship. Previous research has proposed positive affect impacts health by reducing inflammation and cortisol while improving behavioral flexibility and broadening attention and cognition, and that negative affect compromises health by increasing inflammation and pain-related fear (Hanssen et al., 2017). These mechanisms need to be more clearly examined as possible targets for pain and sleep interventions. In addition, though we controlled for the influence of hydroxyurea, youth with SCD often take opioid and non-opioid analgesics to manage their pain; and these medications also often have side effects on sleep quality. A diary study of 20 school-age children with SCD indicated that opioid and non-opioid analgesic use was related to poorer sleep quality that night, and that non-opioid use reduces the association between pain severity and sleep quality that night (Valrie et al., 2007a). More research is needed to examine the influence of analgesics on the pain-sleep relationship in adolescents with SCD, and how analgesic use may relate to affective reactions to pain and sleep in the population.

Clinically, the findings highlight that enhancing positive affect, and reducing negative affect, as part of pain interventions in youth with SCD, and possible other pain populations, may improve the effectiveness of these interventions. While many chronic pain interventions focus on addressing negative affect, fewer incorporate aspects of positive affect enhancement, such as acceptance commitment therapy (ACT) and mindfulness-based stress reduction (MBSR; (Finan & Garland, 2015). This is despite rising evidence on the effectiveness of ACT for treating chronic pain (Feliu Soler et al., 2018). Also, the use of positive affect enhancement interventions in youth with SCD is very limited. A case study of a 16 year old with SCD provided some evidence that ACT improved functioning and quality of life, but was less clear concerning pain outcomes (Masuda et al., 2011). Also, there is currently a clinical trial focused on examining ACT for adolescents with SCD (Cheng et al., 2013) and another on investigating MBSR for adults with SCD (Williams et al., 2017).

In conclusion, while research has indicated that affect does play a significant role in the relationship between sleep and pain in pediatric pain populations, previous research has failed to investigate the distinct influences of positive and negative affect on the sleep-SCD pain relationship. The current study addresses gaps in the literature by utilizing a micro-longitudinal design to examine the differential influence of positive and negative affect on the daily cyclic relationship between subjective sleep quality and SCD pain severity. Low positive affect did mediate the bidirectional relationship between daily poor subjective sleep quality and high SCD pain severity. In addition, high negative affect strengthened the relationship between high pain severity and poor sleep that night. While this study does help to highlight the differential roles of positive and negative affect in relation to sleep and pain in youth with SCD, further research is needed to examine if the role of positive and negative affect remains the same in other pediatric pain populations, as well as adult SCD populations. Furthermore, understanding the process by which positive and negative affect work to influence the sleep-pain relationship may yield vital information to inform sleep and pain intervention development for youth with SCD.

Acknowledgments

This work was supported by funding from the National Heart, Lung, and Blood Institute of the National Institutes of Health (Grant number NIHK01HL103155), and the American Society of Hematology. The authors acknowledge the work of Dr. Rupa Redding-Lallinger, M.D., who assisted with early project conceptualization and participant recruitment.

Footnotes

There are no known conflicts of interest to disclose.

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