Psychological Predictors of Pain in Children and Adolescents With Sickle Cell Disease: A Scoping Review

Abstract

Objective: Sickle cell disease (SCD) is a common red blood cell disorder that disrupts the lives of many African Americans and those of Middle Eastern heritage within the United States due to frequent pain. There is limited research quantifying biopsychosocial factors, specifically psychological characteristics, that influence pain in children and adolescents with SCD. The aim of this literature review was to identify psychological characteristics that are predictive or associated with pain in children and adolescents with SCD. Method: This review was conducted using PRISMA guidelines. Four databases, PubMed, CINAHL, PsycINFO, and Scopus, were searched using specific terms to address the aim of the review (SCD, pain, pediatrics and adolescents, and psychological characteristics). Results: The review identified a lack of consensus regarding the definitions and measurement of pain frequency and intensity. A variety of psychological characteristics were associated with pain including coping strategies, anxiety, depressive symptoms, catastrophizing, and stress. Overall, the study designs restricted the ability to fully identify psychological characteristics that predict pain. Conclusions: Health science researchers must strive for a deeper understanding about the presentation of SCD pain and psychological risk factors associated with increased pain to provide targeted screening and treatment.

Sickle cell disease (SCD) is the most commonly inherited red blood cell disease in the United States, affecting one in 375 African Americans (Norman & Miller, 2011; Vacca & Blank, 2017). Those with SCD have genetic mutations resulting in misshapen red blood cells that easily adhere to each other within blood vessel walls, resulting in vaso-occlusion. Several complications arise from vaso-occlusion including organ damage, and cardiovascular and pulmonary complications (Vacca & Blank, 2017). Additionally, inflammatory mediators are released from the vaso-occlusive site resulting in acute nociceptive pain also known as a vaso-occlusive crisis (Ballas, Gupta, & Adams-Graves, 2012). Vaso-occlusive crises are the most common reason for hospitalization among patients with SCD (Treadwell, Hassell, Levine, & Keller, 2014; Zempsky et al., 2017). Although vaso-occlusive crises cause acute pain, emerging literature within the SCD population has sought to understand the neurobiology of chronic sickle cell pain.

In addition to acute nociceptive pain manifested as vaso-occlusive pain crises, 37% to 40% of adults with SCD report chronic pain (also termed neuropathic pain; Brandow, Farley, & Panepinto, 2015). Chronic pain is defined as recurrent pain lasting longer than 3 months that develops due to dysfunction within the central nervous system (Merskey & Bogduk, 1994). One study conducted in adults with SCD showed that 55% of patients reported pain for up to 6 months (based on data from daily pain diaries) and reported pain on more than half of the diary days (Smith et al., 2008).

Several studies have identified biological variables that predict pain frequency and severity including age and sickle cell genotype (Brousseau, Owens, Mosso, Panepinto, & Steiner, 2010; Gill et al., 1995; Platt et al., 1991). As children with SCD grow older, the frequency and intensity of their pain increases (Brandow, Farley, Dasgupta, Hoffmann, & Panepinto, 2015; Zempsky et al., 2017). Also, those with HbSS and HbSβ0 tend to have a more severe pain and disease presentation (Dampier, Ely, Brodecki, & O’Neal, 2002; Gill et al., 1995; Platt et al., 1991). Although understanding the biological predictors of SCD pain is necessary to develop targeted pain interventions for those with SCD as they age or present with more severe genotypes, biological factors are not the only factors that perpetuate chronic pain. Research evidence about chronic pain in children and adolescents identifies psychological characteristics such as maladaptive coping, anxiety, depressive symptoms, and fear as factors that confound chronic pain (Landry et al., 2015). This highlights the need to identify the psychological factors that predict pain in children and adolescents with SCD.

Without understanding the impact psychological factors have on pain, a complete understanding of chronic pain and those most affected would be impossible (Gatchel, Peng, Peters, Fuchs, & Turk, 2007). Theoretical models suggest that variability in pain perception can be explained by an interaction between physiologic, psychologic, and situational influences (Edwards, Campbell, Jamison, & Wiech, 2009; Keefe & France, 1999; Lenz, Pugh, Milligan, Gift, & Suppe, 1997). Thus, the purpose of this literature review was to use a biopsychosocial approach, specifically identifying psychological variables that are linked with pain perception in children and adolescents with SCD and to critically appraise the quality of the studies identified. If evidence suggests that certain psychological factors place a child or adolescent more at risk for developing chronic pain in adulthood, improved screening and behavioral interventions can be implemented by clinicians. If proven effective, these interventions could reduce health care costs and opioid prescriptions. Therefore, the research question guiding this search was “which psychological characteristics are associated with or predict pain in children and adolescents with SCD?”

Method

This literature review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria (PRISMA; Moher, Liberati, Tetzlaff, Altman, & PRISMA Group, 2009). The population targeted was children, adolescents, and young adults aged 0 to 22 years with SCD. Additionally, articles were included if they were written in English, and identified pain as a primary outcome and mental health characteristics as contributing factors. All articles were included regardless of year published. The databases searched throughout this review were PubMed, CINAHL, PsycINFO, and Scopus. References of the articles included were not searched for additional articles. The searches began on September 12, 2017 and ended on October 18, 2017.

Phrases, synonyms, and MESH headings of each of the search terms were included to broaden the search. An example of the search strategy used within PubMed is shown in Table 1. A broad definition of pain was utilized within the search strategy to ensure a comprehensive literature review. This definition included pain frequency, intensity, severity, sensitivity, and hospitalizations for pain. The titles and abstracts of all deduplicated articles were reviewed to determine if they met the inclusion criteria (N = 526). After title and abstract review, 67 articles were included and further assessed for their applicability to the population and targeted phenomena (SCD, children and adolescents, pain, and psychological characteristics). Following full text review, 19 articles fit the inclusion criteria. A PRISMA flow diagram is shown in Figure 1 to depict the number of articles retrieved as well as those included and excluded. Data extraction of the 19 articles was completed independently by the first author. A second reviewer was consulted to confirm the inclusion of the articles identified (see Table 2).

Table 1.

Example of Search Strategy Utilized Within PubMed Database.

Search term	Search strategy
Sickle cell disease	“anemia, sickle cell”[MeSH Terms] OR (anemia[tiab] AND sickle[tiab] AND cell[tiab]) OR “sickle cell anemia”[tiab] OR (“sickle”[tiab] AND “cell”[tiab] AND “disease”[tiab]) OR “sickle cell disease”[tiab] OR “sickle cell anaemia”[tiab] OR “beta thalassaemia”[tiab] OR “beta-thalassemia”[MeSH Terms] OR “beta-thalassemia”[tiab] OR (“beta”[tiab] AND “thalassemia”[tiab])
Pain	“Pain Perception”[Mesh] OR “Pain”[Mesh] OR Pain [tiab] OR painful[tiab] OR discomfort[tiab] OR “Pain Measurement”[Mesh] OR “Analgesia Test”[tiab] OR Nociception[tiab] OR Nociceptive[tiab]
Children and adolescents	Infant[MeSH] OR Infant[tiab] OR Infants[tiab] OR infancy[tiab] OR Newborn[tiab] OR Newborns[tiab] OR Baby[tiab] OR Babies[tiab] OR Neonatal[tiab] OR Neonate[tiab] OR Child[MeSH] OR Child[tiab] OR children[tiab] OR Schoolchild OR “School age”[tiab] OR Preschool*[tiab] OR Kid[tiab] OR kids[tiab] OR Toddler*[tiab] OR Adolescent[MeSH] OR Adolescent[tiab] OR Adolescents[tiab] OR Adolescence[tiab] OR Teen[tiab] OR teenager[tiab] OR teens[tiab] OR Boy[tiab] OR boys[tiab] OR Girl [tiab] OR girls[tiab] OR Minors[MeSH] OR Minors[tiab] OR Pediatrics[MeSH] OR Pediatric[tiab] OR Pediatrics[tiab] OR Paediatrics[tiab] OR youth[tiab] OR “Young Adult”[Mesh] OR childhood[tiab]
Psychological characteristics	“Adaptation, Psychological”[Mesh] OR “anxiety”[MeSh Terms] OR anxiety[tiab] OR anxious[tiab] OR Nervousness[tiab] OR Hypervigilance[tiab] OR anxieties[tiab] OR “Catastrophization”[Mesh] OR Catastrophizing[tiab] OR Catastrophization[tiab] OR “Emotions”[Mesh] OR “Affect”[Mesh] OR “Affective Symptoms”[Mesh] OR “Stress Disorders, Traumatic”[Mesh] OR Traumatic[tiab] OR trauma[tiab] OR “Behavioral Symptoms”[Mesh] OR “Depression”[Mesh] OR depression[tiab] OR depressive[tiab] OR depressed[tiab] OR “Violence”[Mesh] OR violence[tiab] OR IPV[tiab] OR abuse[tiab] OR abused[tiab] OR rape[tiab] OR raped[tiab] OR “Crime Victims”[Mesh] OR Psychological[tiab] OR mental[tiab]

Figure 1.

PRISMA flow diagram.

Table 2.

Literature Tables of Evidence.

Author (published year)	Study type	Sample size	Population	Setting	Aim	Measures	Findings	Psychological predictors	JBI level of evidence
Bakshi et al.(2017)	Case control	N = 29 and 26 controls	SCD aged 8-21 years	Sickle cell clinic	To identify the relationship of psychological covariates to experimental pain sensitivity in children with SCD compared with healthy controls.	Pain intensity and unpleasantness: Situational PCS in relation to experimental stimuli Quantitative sensitive testing: Pressure sensitivity, mechanical sensitivity, and thermal sensitivity Clinical pain burden: Number of ED visits and admissions Pain interference, anxiety, depressive symptoms, fatigue, and peer relationships: PROMIS measures Pain catastrophizing scale Revised child somatization inventory PedsQL	Anxiety, depressive symptoms, catastrophizing and somatization were associated with increased sensitivity to experimental pain stimuli. Increased frequency of painful episodes was associated with decreased sensitivity to heat pain and decreased mechanical temporal summation. No difference in scores of psychological measures between those with SCD and controls.	Anxiety Depressive symptoms Catastrophizing Somatization	3d
Wakefield et al. (2017)	Cross-sectional	N = 28	SCD aged 13-21 years	Outpatient and inpatient settings	To determine the frequency of perceived racial bias and health-related stigma in adolescents and young adults with SCD and to understand how they are related to the psychological and physical well-being.	Pain severity classification: Number of pain episodes in past 2 years Sickle cell pain burden interview-youth Perceptions of racism in children and youth Child stigma scale Centers for Epidemiologic Studies Depression Scale PedsQL	A total of 96.4% reported perceived racial bias events with community settings and 14.3% within medical settings. A moderately positive relationship was found between perceived racial bias and pain burden. Perceived health-related stigma was positively correlated with perceived racial bias scores. Lower QOL was found with more perceived health-related stigma; 75% of sample endorsed clinically significant levels of depression.	Pain burden Perceived racial bias	4b
Zempsky et al. (2017)	Cross-sectional	N = 156	SCD aged 7-21 years	4 Children hospitals; inpatient	To identify if youth with widespread pain have higher pain scores, longer lengths of stay, more functional disability, pain, pain burden, decreased mood, and impaired QOL.	Pain location: Adolescent pediatric pain tool Pain frequency: Pain days in the past month (parent or child report) Widespread pain: WSP index Pain intensity: Average pain score during hospitalization Positive affect negative affect scale for children Sickle cell pain burden interview youth Child activity limitations interview	A total of 21.8% had widespread (pain in seven or more unique body locations). These patients had higher pain intensity, pain burden, higher acute functional disability, higher chronic functional disability, lower positive affect, and lower QOL.	Pain burden QOL Positive affect	4b
Schlenz et al. (2016)	Cross-sectional	N = 76	Children with SCD aged 8-19 years and caregivers	Outpatient clinic	To examine biological (SCD genotype), psychological (child coping and mood), and social factors (caregiver coping and family functioning) in relation to multiple pain features to determine their relative and combined associations with pain in children with SCD.	Health care utilization, average duration, and average intensity: Pain history interview Pain frequency: Number of pain episodes and those that required a medical visit (parent and child report was moderately associated for frequency, intensity and duration; child and caregiver ratings were averaged to avoid over or underestimation of pain) Coping Strategies Questionnaire for SCD Positive and Negative Affect Scale Coping Strategies Questionnaire-Revised (Caregiver) McMaster Family Functioning Assessment Device (Caregiver)	Child negative thinking was positively associated with pain frequency and health care utilization and approached significance with pain intensity and duration. Child positive mood was negatively associated with pain frequency, duration, and health care utilization. Results suggest that reports of pain vary between reported (only some were significant).	Coping Mood	4b
Sil et al. (2016)	Cross-sectional	N = 100 (n = 40 chronic, n = 40 episodic, n = 20 no pain)	SCD children and adolescents aged 8-18 years	Outpatient sickle cell clinic	To characterize difference in functional outcomes, psychosocial characteristics and health care utilization in patients with chronic pain, episodic pain and no SCD-related pain in past month.	Pain intensity and frequency: Patients reported on average pain in past 2 weeks and patients and parents reported on pain days in past month Pain Catastrophizing Scale–Child Pediatric survey of pain attitudes Functional Disability Inventory PedsQL-SCD Children’s Depression Inventory–2 Health care utilization: number of hospitalizations, and ED visits related to pain within past year	Those in the chronic SCD pain group missed 35.93 (SD = 43.81) days of school due to pain within the past year compared with episodic and no pain groups. Patients in the chronic pain group were significantly older than those in the no SCD pain group. Chronic pain group had higher levels of functional disability, greater depressive symptoms (mild range) than those in episodic, and more hospital admissions (2 × amount of episodic). Significant differences between pain, catastrophizing, and QOL between the no pain and pain groups. No significant difference between groups for ED visits for pain.	Depressive symptoms Catastrophizing QOL	4b
Ezenwa et al.(2015)	Cross-sectional; pilot	N = 52	Three groups SCD; aged 18-25 years; 26-45 years; >46 years	Sickle cell clinic	To examine the relationship of perceived injustice with perceived stress and pain in adults with SCD.	Pain location, intensity, quality and pattern: PainReportIt composite pain index Perceived Injustice Questionnaire–Revised: adapted to SCD Perceived Stress Questionnaire–general	Perceived injustice from doctors was significant predictor of perceived stress and pain. Perceived injustice from nurses was also a significant predictor of perceived stress and pain. Procedural and distributive domains of perceived injustice consistently predicted patients’ pain.	Perceived injustice Stress	4b
Schatz et al. (2015)	RCT (CBT skills training or waitlist)	N = 46 (and their caregivers)	SCD aged 8-21 years	Two SCD specialty clinics	To describe the primary outcomes of a pain management intervention for pediatric SCD that involved a single session of CBT skills training followed by home-based practice using smartphones.	Pain history interview: pain episodes in the previous year Pain frequency and intensity: electronic daily pain and activity diary Quality of CBT training Coping Strategies Questionnaire for SCD	When children used CBT skills on days with higher pain, there were reductions in next-day pain intensity (diary log not patient report). Intervention group: Increased beliefs in pain controllability but no change in negative thinking in response to pain.	Coping	1c
Graves and Jacob (2014)	Cross-sectional	N = 66	SCD aged 10-12 years	Sickle Cell Disease Foundation of California population	To examine relationships among pain, pain coping, and sleep, and to assess factors such as age, gender, frequency, and severity of pain episodes that may have significant effects on pain, pain coping, and sleep.	Pain Intensity: Visual Analog Scale Pain Frequency: Number of pain episodes in the previous 12 months (parent report) Pediatric Coping Questionnaire Pittsburg Sleep Quality Index	Pain frequency and pain severity did not have significant effects on pain coping. No significant correlations between worst pain severity and pain coping the previous month. Significant negative correlations in males between worst pain severity and positive behavioral distraction and negative internalizing/catastrophizing, but not in females.	Coping	4b
Tsao et al. (2014)	Cross-sectional	N = 69 (infrequent hospitalizations n = 51; frequent hospitalizations n = 18)	SCD aged 10-17, years	Community-based organization in Southern California	To investigate the relationships among emotion regulation, somatization, positive and negative affect, and the frequency of hospitalization for vaso-occlusive pain crises in youth with SCD	Pain hospitalizations: pain crises in past 12 months, and those requiring hospitalization (parent report) Positive and Negative Affect Scale for Children Children’s Somatization Inventory ERQ-CA: Emotional regulation strategies	Those with SCD subtype HgbSC scored significantly higher on somatization inventory than HgbSS. Frequent hospitalization group reported more pain, higher somatization, and higher emotional suppression.	Somatization Emotional suppression	4b
Zempsky, Palermo, et al. (2013)	Longitudinal	N = 25	SCD aged 11-20 years	Inpatient unit	To characterize changes in daily pain intensity, physical function and mood over the course of hospitalization, and to determine whether specific clinical characteristics were associated with these changes.	Pain Intensity: Numeric Response Scale by the nurse every 4 hours during hospitalization Functional Independence Measure Positive and Negative Affects Schedule–Child Version Opioid use during hospitalization	Positive affect was not significantly associated with pain scores. Unlike positive affect, negative affect was significantly associated with pain scores.	Mood	3e
Jerrell et al. (2011)	Cohort study	N = 2,194	Medicaid claims data; Those with SCD aged 0-17 years	Medicaid claims data	To describe the prevalence and treatment of comorbid depressive disorders in children and adolescents diagnosed with SCD.	International Classification of Diseases codes; Diagnostic and Statistical Manual of Mental Disorders–IV codes for depression	Indeed, 46% diagnosed with depressive disorder: Dysthymia (90%) or major depressive disorder (10%). Those diagnosed with depression were more likely to have vaso-occlusive pain and other complications, >80% were not prescribed antidepressants.	Depression diagnosis	3d
Valrie et al.(2008)	Longitudinal	N = 20	SCD aged 8-12 years	Two outpatient clinics	To investigate mood as a mediator or moderator of the pain–sleep relationship in children with SCD.	Pain Frequency and Intensity: Daily Diary Facial Affective Scale Sleep Quality: Daily Diary	Negative mood was associated with high-pain severity that day. Negative mood partially mediated the relationship between high daily pain and poor sleep quality that night and the following day.	Mood	3e
Barakat et al. (2007)	Prospective	N = 52	SCD aged 12-18 years	Sickle cell center at an East Coast Children’s Hospital	To examine the association of teen-reported pain frequency, intensity, and interference with daily activities and school activities with symptoms of depression and anxiety, and to determine the role of pain coping strategies in mediating the association of pain with symptoms of depression and anxiety.	Perceived frequency, intensity, and interference: Varni/Thompson Pediatric Pain Questionnaire Pain, health care utilization, medication use, and pain interference: Daily Pain Diary Coping Strategies Questionnaire–Revised Children’s Depression Inventory Revised Children’s Manifest Anxiety Scale	Negative thinking mediated the association of pain intensity with depression and pain interference with daily activities with anxiety. Overall, those who had greater pain frequency, intensity, and interference reported more symptoms of depression and anxiety.	Negative thinking (coping) Depression Anxiety	3e
Hoff et al. (2006)	Longitudinal	N = 119 (n = 56 SCD)	SCD and juvenile idiopathic arthritis children aged 8-17 years	Hematology and rheumatology clinics	To examine the longitudinal relationship between depressive symptoms at study entry on pain intensity and functional disability among children with SCD or juvenile idiopathic arthritis over a 1-year period.	Pain intensity: Faces Pain Scale Functional Disability Inventory Revised Child anxiety and Depression Scale Provider assessment: Disease classification, medications, and perception of disease severity	SCD: Weekly pain in 47.4% (T1), 17.1% (T2), and 28.2% (T3). Girls reported significantly greater pain intensity than boys. Depressive symptoms did not significantly predict child-reported pain intensity or functional disability for children with SCD.	Depressive symptoms	3e
Gil et al. (2003)	Prospective	N = 37	SCD adolescents aged 13-17 years	University sickle cell clinics	To prospectively analyze daily patterns of pain, stress and mood in adolescents with SCD.	Pain frequency, intensity and duration: Daily Diary for presence of pain, intensity with Visual Analogue Scale and health care usage School and activity: Stayed home from school, extracurricular, household chores during pain Perceived stress level: Visual analogue scale Mood Scale: Positive and negative affect Adolescent Daily Hassles Scale Psychological distress: Symptom Checklist-90–Revised	Increase of stress on a day-to-day basis was significantly associated with increases in pain. Increases in negative mood were significantly related to increases in pain. Increases in higher stress and higher other pain was associated with increase in SCD pain. High positive mood was associated with lower levels of SCD pain.	Stress Mood	3e
Anie et al.(2002)	Cross-sectional	N = 67	SCD children aged 7-15 years	Three hospitals	To examine relations between pain, coping, and health service utilization.	Pain frequency: Number and duration of pain episodes within 12 months Health service utilization: Visits to ED, number and duration of admissions, and consultations Coping: Coping strategies questions for SCD (CSQ-SCD)	Children with HbSS had more intense pain than others (p = .022). Pain frequency and severity were associated with health service utilizations. Pain severity is associated with passive adherence coping.	Passive adherence coping	4b
Gil et al. (2001)	RCT (coping skills condition or standard care-control condition)	N = 46 (n = 26 coping skills condition; n = 20 standard care control condition)	SCD children aged 8-17 years	Outpatient sickle cell clinics from three hospitals	To examine the 1-month effects of a pain coping skills intervention in children with SCD.	Pain intensity: Daily Pain Diary Pain sensitivity: Forgione–Barber focal pressure stimulator Pain frequency: Daily Pain Diary and parents were asked to recall pain and health care use at follow-up and compared this with daily diary Daily Pain Diary: Pain intensity, frequency, medication use, health care use Coping Strategies Questionnaire Children’s Depression Inventory Revised Children’s Manifest Anxiety Scale	No significant differences between groups regarding pain sensitivity, frequency, duration, or health care contacts at 1-month follow-up. Children in coping skills condition reported that they took a significantly more active approach to manage their pain than those in the control condition. Higher pain combined with greater coping was significantly related to decreases in major health care contacts (ER, hospitalizations, or clinic visits) for those in the coping condition. This was not statistically significant for phone calls to physicians or medication use.	Coping	1c
Gil et al. (1997)	Cross-sectional	N = 41	SCD aged 8-17 years	University sickle cell center	To analyze relationships between pain and coping strategies, depression, and anxiety.	Pain sensitivity: Forgione–Barber focal pressure stimulator Stimulus response data: Sensory decision theory procedures Pain frequency and duration: Parent Structured Pain Interview Pain quality: McGill Pain Questionnaire Coping Strategies Questionnaire Children’s Depression Inventory Missouri Children’s Behavior Checklist Revised Children’s Manifest Anxiety Scale Sickle cell complications	Significant correlation between number of complications and report criterion of pain. Those who reported using active coping had a lower tendency to report pain during the laboratory pain task. More active coping strategies had significantly poorer sensory discrimination. Poor sensory discrimination was significantly related to depression and externalizing behavior problems. Lower tendency to report pain was also significantly related to depression. No significant relationship between pain sensitivity and anxiety.	Coping Depression Anxiety	4b
Gil et al. (1993)	Longitudinal	N = 70	Children and adolescents with SCD, aged 7-18 years	Two comprehensive sickle cell centers and their three outreach clinics	To determine the extent to which pain coping strategies measured at one point in time predict subsequent adjustment. To examine the stability and change over time in the number of painful episodes and disease complications. To investigate the stability and change over time in pain coping strategies.	Coping Strategies Questionnaire for SCD Structured Pain Interview Pain frequency, duration, and intensity: answered by adolescents and parents (significant correlations for pain intensity, hospitalizations and their duration; no reports for pain duration or frequency or for the correlation with child’s responses)	Children that scored high on passive adherence had more frequent contact with health care providers while those with high-coping attempts tended to have less frequent health care contacts; however, this was not significant.	Coping	3e

Note. SCD = sickle cell disease; JBI = Joanna Briggs Institute; QOL = quality of life; RCT = randomized control trials; CBT = cognitive behavioral training.

Critical Appraisal

Joanna Briggs Institute (JBI) Levels of Evidence (2014) were used to compare strengths of study design graded from Level 1 through Level 5. Research studies that are graded as Level 1 are those with the strongest research design. Additionally, JBI critical appraisal tools were selected based on relevant checklists available for case-control, cohort studies, and cross-sectional studies. These checklists were used to evaluate the studies’ methodological design and the risk of bias (Joanna Briggs Institute Critical Appraisal Tools, 2017).

Results

Psychological Characteristics and Pain

Several studies examined the relationship among a variety of psychological characteristics and SCD-associated pain including depressive symptoms or depression, anxiety, coping, stress, catastrophization, pain burden, quality of life (QOL), mood, somatization, emotional suppression, and perceived racial bias and injustice (Anie et al., 2002; Bakshi et al., 2017; Barakat et al., 2007; Ezenwa et al., 2015; Gil et al., 1993; Gil et al., 1997; Gil et al., 2001; Gil et al., 2003; Graves & Jacob, 2014; Hoff et al., 2006; Jerrell et al., 2011; Schatz et al., 2015; Schlenz et al., 2016; Sil et al., 2016; Tsao et al., 2014; Valrie et al., 2008; Wakefield et al., 2017; Zempsky, Palermo, et al., 2013; Zempsky et al., 2017).

Six studies within this review included depressive symptoms or a depression diagnosis as a psychological factor associated with increased pain sensitivity, frequency, and intensity, and clinical pain burden (Bakshi et al., 2017; Barakat et al., 2007; Gil et al., 1997; Hoff et al., 2006; Jerrell et al., 2011; Sil et al., 2016). While associations were found with all these studies, only three studies utilized a longitudinal study design (Barakat et al., 2007; Hoff et al., 2006; Jerrell et al., 2011). In addition to depression, three studies also measured anxiety. Research evidence from one study suggests an association between anxiety and pain frequency (Barakat et al., 2007), while two studies had conflicting results for the association between anxiety and increased pain sensitivity (Bakshi et al., 2017; Gil et al., 1997).

Eight of the studies measured coping within their study designs in terms of active and passive coping strategies. Active coping strategies refer to actions taken by the patient to gain control over the pain, while passive coping refers to withdrawal, avoidance, and a feeling of hopelessness in the patient causing them to rely on others to resolve the stressor (Snow-Turek, Norris, & Tan, 1996). Research evidence suggests that active coping strategies were associated with decreased pain sensitivity (Gil et al., 1997) and health care utilization (Gil et al., 1993), while passive adherence coping was associated with an increase in pain severity (Anie et al., 2002), pain frequency (Schlenz et al., 2016), and health care utilization for pain (Gil et al., 1993; Schlenz et al., 2016). One study identified that poor coping, or negative thinking, mediated the association of pain intensity with depression and pain interference (Barakat et al., 2007). Additionally, one study found a significant association between coping and pain severity in males but not females (Graves & Jacob, 2014). Four of the studies that measured coping utilized cross-sectional study designs (Anie et al., 2002; Gil et al., 1997; Graves & Jacob, 2014; Schlenz et al., 2016), while one was prospective (Barakat et al., 2007), one was longitudinal (Gil et al., 1993), and two were randomized control trials (RCT; Gil et al., 2001; Schatz et al., 2015).

The two RCT identified within this review tested coping-based educational interventions and analyzed differences between those that received the training and those that did not (Gil et al., 2001; Schatz et al., 2015). One intervention utilized smartphones to provide coping and cognitive behavioral training (CBT) to SCD patients (Schatz et al., 2015). Children that used CBT skills on days with higher pain had reductions in next-day pain intensity. Furthermore, those who received CBT skills training had increased beliefs in pain controllability but reported no change in negative thinking in response to pain (Schatz et al., 2015). The second RCT (Gil et al., 2001), which tested a coping skills intervention compared with a control condition, found no significant differences between the intervention and control groups regarding pain sensitivity, frequency, duration, or health care utilization (Gil et al., 2001). However, those with higher pain that used more coping strategies, had decreases in health care utilization (Gil et al., 2001).

Another concept identified within the studies was stress. Two studies chose to evaluate the relationship between stress and pain and found that increase in stress was associated with increased pain frequency and composite pain scores (Ezenwa et al., 2015; Gil et al., 2003). One of these studies utilized a prospective study design with daily pain diaries (Gil et al., 2003), while the other was cross-sectional (Ezenwa et al., 2015).

Catastrophization and pain burden were two psychological variables chosen in four of the articles within this review (Bakshi et al., 2017; Sil et al., 2016; Wakefield et al., 2017; Zempsky et al., 2017). Two cross-sectional studies reported an association between catastrophization and increased pain frequency and sensitivity (Bakshi et al., 2017; Sil et al., 2016). One cross-sectional study evaluated the relationship between widespread body pain and pain burden and found that those with widespread body pain, a manifestation of neuropathic pain, had higher pain burden (Zempsky et al., 2017). An additional study investigated the associations between perceived racial bias and pain burden and reported that an increase in perceived racial bias was positively correlated with an increase in pain burden (Wakefield et al., 2017). Both of the studies used the same measure for pain burden (Wakefield et al., 2017; Zempsky et al., 2017) which assesses pain frequency as well as the impact of pain on physical functioning, social interaction, and emotional aspects of daily living (Zempsky, O’Hara et al., 2013).

QOL and mood were associated with pain based on the findings from six studies included in this review (Gil et al., 2003; Schlenz et al., 2016; Sil et al., 2016; Valrie et al., 2008; Zempsky, Palermo, et al., 2013; Zempsky et al., 2017). Those with more widespread body pain (Zempsky et al., 2017) and more pain frequency (Sil et al., 2016) were found to have lower QOL and lower positive affect. Positive mood was negatively associated with pain frequency (Gil et al., 2003; Schlenz et al., 2016), pain duration (Schlenz et al., 2016), and health care utilization (Schlenz et al., 2016); however, positive mood was not associated with decreased pain intensity (Zempsky, Palermo, et al., 2013). In addition, increases in negative mood was significantly associated with increases in pain intensity (Gil et al., 2003; Schlenz et al., 2016; Valrie et al., 2008). Half of these studies assessed positive or negative mood longitudinally (Gil et al., 2003; Valrie et al., 2008; Zempsky, Palermo, et al., 2013),

Psychologic characteristics that were infrequently identified throughout the literature in their relation to pain were somatization, emotional suppression, and perceived racial bias and injustice. Somatization, measured via the Children’s Somatization Inventory, as well as emotional suppression (Tsao et al., 2014) was found to be associated with increased pain sensitivity (Bakshi et al., 2017) and with patients with more hospitalizations for pain (Tsao et al., 2014). Reports of high-perceived racial bias (Wakefield et al., 2017) and perceived injustice (Ezenwa et al., 2015) were associated with increase in pain burden and pain composite scores. Although significant relationships were found between these psychological characteristics and pain, three of these studies were purely cross-sectional (Ezenwa et al., 2015; Tsao et al., 2014; Wakefield et al., 2017), while one utilized a cohort study design (Bakshi et al., 2017).

Other Findings

Most of the articles reported measures of pain frequency as either the amount of health service utilization or the number of pain days reported by the patient (Anie et al., 2002; Bakshi et al., 2017; Barakat et al., 2007; Gil et al., 1997; Gil et al., 2003; Graves & Jacob, 2014; Jerrell et al., 2011; Schlenz et al., 2016; Sil et al., 2016; Tsao et al., 2014; Valrie et al., 2008; Wakefield et al., 2017; Zempsky et al., 2017). Patient- or parent-reported pain days was a commonly used outcome measure (Barakat et al., 2007; Gil et al., 1997; Gil et al., 2001; Gil et al., 2003; Graves & Jacob, 2014; Schatz et al., 2015; Schlenz et al., 2016; Sil et al., 2016; Tsao et al., 2014; Zempsky et al., 2017). Five studies prospectively assessed pain frequency using daily pain diaries (Barakat et al., 2007; Gil et al., 2001; Gil et al., 2003; Schatz et al., 2015; Valrie et al., 2008). However, other researchers operationalized pain frequency retrospectively by the number of emergency department visits or hospitalizations within a given time (Anie et al., 2002; Bakshi et al., 2017; Graves & Jacob, 2014; Jerrell et al., 2011; Schlenz et al., 2016; Tsao et al., 2014; Wakefield et al., 2017).

Pain intensity or pain severity was measured in a variety of different ways. In 6 of the 19 articles, several different measurement methods were used to capture pain intensity. Sensitivity to pressure (e.g., Kilograms of pressure are applied to the skin using an algometer and patients indicate the pressure level that causes pain), mechanical (e.g., von Frey filaments of varying thickness are applied to the skin and patients indicate which filament causes pain), or thermal stimuli were used to evaluate pain perception in three studies (Bakshi et al., 2017; Gil et al., 1997; Gil et al., 2001). Pain severity was assessed using an average hospital pain score, average outpatient-rated pain scores obtained over a 2-week period, pain history interviews, daily pain diaries, and four validated pain measures: PAIN Report It, Visual Analog Scale, Numeric Response Scale, and the Faces pain scale (Bakshi et al., 2017; Barakat et al., 2007; Ezenwa et al., 2015; Gil et al., 1993; Gil et al., 2003; Graves & Jacob, 2014; Hoff et al., 2006; Schatz et al., 2015; Schlenz et al., 2016; Sil et al., 2016; Valrie et al., 2008; Zempsky, Palermo, et al., 2013; Zempsky et al., 2017).

Additionally, there was conflicting evidence about whether parent-reported pain should be utilized as a proxy-measure of a child’s pain. Three articles within this review utilized parent-reports as the sole measure of pain frequency (Graves & Jacob, 2014) and clinical pain burden (Tsao et al., 2014; Zempsky et al., 2017). However, other studies highlighted inconsistencies between patient-report and parent-reports of pain frequency, intensity, and duration (Gil et al., 1993; Schlenz et al., 2016; Sil et al., 2016).

Discussion

SCD is a complex disease and no single psychological characteristic fully predicts pain frequency or severity within the population. There were 11 psychological characteristics found to be predictive of or associated with pain within the studies reviewed: depressive symptoms/depression, anxiety, coping, stress, catastrophization, pain burden, QOL, mood, emotional suppression, and perceived racial bias and injustice. Although the literature described in this review was useful when addressing the research question, “How are psychological characteristics associated with or predict pain in children and adolescents with SCD?” There were no studies that utilized a theoretical framework to explore a comprehensive set of factors that could influence pain. In addition to psychological characteristics, there are many biological and social factors that may also influence pain perception in children and adolescents with SCD including age, gender, subtype of SCD, access to care, and continuity of care. Utilizing a theoretical framework to guide predictive research in this population will allow for a more thorough understanding of the biopsychosocial factors that interact with each other to influence the pain presentation.

One limitation of the published literature is that a wide variety of measurement tools were used to quantify pain and psychological characteristics, which complicated the synthesis and interpretation of findings. Additionally, the measurement tools were not fully validated in all the samples within the studies; for example, studies that included patients aged 18 to 21 years still utilized pediatric measures. Furthermore, there was no commonality regarding how to define pain variables. Use of commonly accepted definitions for pain severity and frequency would allow comparison of results across studies. Half of the published findings were generated using cross-sectional study designs, limiting the ability to describe relationships or cause and effect. Only two of the studies were RCTs, both of which evaluated one of the psychological characteristics, coping, and its association with pain. Additionally, many of the studies evaluating the relationship among coping, mood, and pain had conflicting results. More studies are needed that utilize prospective, experimental designs so that new knowledge regarding the efficacy of interventions to ameliorate SCD-related pain can be discovered in the future. Additionally, the use of daily pain diaries would provide more robust information regarding the pain presentation including pain onset, frequency, location, and severity.

A single reviewer synthesized the findings of this review, thus there was a risk of bias throughout the review process. Despite this limitation, this review utilized a systematic approach to review and critically appraise the articles included. Additionally, the authors used a biopsychosocial approach to discover a major gap within the literature regarding factors associated with chronic SCD pain in children and adolescents. While psychological factors were found to be associated with increase pain within this population, no studies utilized a comprehensive theoretical framework to identify the possible psychological, biological, and social factors that interact each other to affect pain. A longitudinal study design investigating the biological, social, and psychological factors that predict acute and chronic pain using self-report daily pain diaries in children and adolescents with SCD is essential to learning more about the underlying factors that influence pain perception in this population. Once there is a deeper understanding of the factors that place patients with SCD more at risk for pain, targeted and individualized screening and treatment interventions can be developed and tested using experimental designs to improve pain outcomes.

Author Biographies

Clare Donohoe, BSN, RN, is a doctoral student at the University of Michigan School of Nursing in Ann Arbor, MI.

Ellen Lavoie Smith, PhD, APRN, AOCN®, FAAN, is an associate professor of nursing and the Director of the PhD program at the University of Michigan School of Nursing in Ann Arbor, MI.