A Review of the Literature on the Multiple Dimensions of Chronic Pain in Adults with Sickle Cell Disease

Abstract

Sickle cell disease (SCD) is a major healthcare and societal problem that affects millions of people worldwide. In Nigeria, 45,000 to 90,000 babies are born each year with SCD. In the United States, SCD is the most common genetic disorder, affecting more than 80,000 people, the majority of whom are African American. Sickle cell pain is the hallmark feature of SCD. Most of the research on pain from SCD has focused on children with acute pain associated with sickle cell crisis. Consequently, very little is known about the occurrence and characteristics of chronic pain, especially in adults with SCD. Individuals with SCD who experience chronic pain are often underserved and their pain is under-treated. This under-treatment may result in millions of dollars per year spent on emergency room visits, hospitalizations, and lost work productivity. The primary purpose of this literature review was to summarize the findings from studies that evaluated the characteristics of chronic pain in adults with SCD. Each of the studies included in this review was evaluated to determine if it provided data on the following multidimensional characteristics of chronic pain: occurrence, number of pain episodes, duration, pattern, quality, location, intensity, aggravating factors, relieving factors, and impact of pain on function. A secondary purpose was to identify gaps in knowledge and directions for future research on the multiple dimensions of chronic pain in adults with SCD.

Introduction

Sickle cell disease (SCD) is a major healthcare and societal problem that affects millions of people worldwide (1). In Nigeria, which has the highest incidence of SCD worldwide, 45,000 to 90,000 babies are born each year with SCD (2). In the United States (US), SCD is the most common genetic disorder; more than 80,000 people are affected, the majority of whom are African American (3). This U.S. prevalence of SCD is likely to be a low estimate because no national registry for SCD exists and statistics are mainly provided for sickle cell anemia, which is the homozygous form of SCD (4). During the years 1979 to 1995, the age adjusted mortality rates for SCD ranged from 0.2 deaths to 14.6 deaths per 1 million persons (5). In 2004, 699 adults with SCD died while hospitalized (6).

Sickle cell pain (SCP) is the hallmark feature of SCD and a measure of its clinical severity (7). Of note, the mortality rate for SCD has been linked to the frequency of sickle cell pain episodes. In one study (8), patients with SCD who were over 20 years of age and experienced more than three pain episodes per year were approximately two times more likely to die earlier than those who had less frequent pain episodes.

In 2004, 83,149 adults were hospitalized in the U.S. for SCD, incurring approximately $488 million in associated costs (6). These figures have increased since 1997, when approximately 75,000 hospitalizations per year for children and adults with SCD yielded a total cost of $475 million (7). One study (9) found a savings of $1.7 million over a five-year period when patients with uncomplicated painful crises from SCD avoided hospitalization through treatment in a day hospital designed specifically for this population. Most hospitalizations of patients with SCD are for a pain crisis. Another study (10) observed that the number of pain episodes was significantly associated (P < 0.001) with the patients’ use of hospital services, even more so than demographic and clinical variables (i.e., co-morbidities, hemoglobin level). A lifetime of unpredictable, recurrent, intense, and frequently persistent pain experiences and the accompanying recurrent use of opioids, make pain associated with SCD unique among pain syndromes (11).

Until the mid 1970s, individuals with SCD did not live past their teens (12). However, due to advances in treatment, the life expectancy of individuals with SCD has tripled from 14 years in 1973 to the current median survival of 42 years for women and 48 years for men (12, 13). Because increased survival is a relatively recent event, most of the research on pain has focused on children with acute, severe pain associated with a sickle cell crisis. Consequently, very little is known about the occurrence and characteristics of chronic pain, especially in adults with SCD. As with children, the majority of studies on pain in adults with SCD has focused on acute pain. In a review of the literature on the pharmacologic management of pain associated with SCD (14), no studies were found that focused on chronic pain.

The limited information available indicates that individuals with SCD who experience chronic pain are often underserved and their pain is under-treated. This under-treatment may result in increased healthcare costs associated with emergency room visits, hospitalizations, and lost work productivity. The primary purpose of this literature review was to summarize the findings from studies that evaluated the characteristics of chronic pain in adults with SCD. Since chronic pain is a multidimensional experience, each of the studies included in this review was evaluated to determine if it provided data on the following characteristics of chronic pain: occurrence, number of pain episodes, duration, pattern, quality, location, intensity, aggravating factors, relieving factors, and impact of pain on function. A secondary purpose was to identify gaps in knowledge and directions for future research on the multiple dimensions of chronic pain in adults with SCD. A multidimensional analysis of chronic pain in adults with SCD is required to more fully understand the nature of the problem and to improve pain assessment and treatment in this population.

Methods

A search of the PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and PsycINFO databases was conducted for all research that evaluated the multiple dimensions of the chronic pain experience of adults (i.e., those 18 years or older) with SCD. The searches were limited to the years 1972 to 2009 because most research on SCD did not take place until after the National Sickle Cell Anemia Control Act was signed into law in 1972 (15). Criteria for study inclusion were: adults with SCD and chronic pain; studies that reported on at least one of the 10 pre-specified dimensions of chronic pain; and research published in English. The determination of chronic pain was based on pain associated with a chronic disorder (e.g., avascular necrosis, chronic bone pain, degenerative disease of the spine) or the definition of chronic pain established by the International Association for the Study of Pain (16), which is pain that persists or recurs for more than three months. Studies were excluded if they evaluated SCP only in children and/or evaluated acute pain unrelated to SCD. Based on this initial screening and a careful review of the reference lists from these studies, 19 studies met the inclusion criteria for this review (8, 10, 17–33).

This literature review provides a summary of the design and methods used in these studies, as well as a summary of the pain dimensions evaluated across these 19 studies of chronic pain in adults with SCD. To summarize the data from the studies, a number of tables were generated that address each dimension of chronic pain in adults with SCD. In addition, to summarize information on a variety of characteristics, weighted means and proportions for a number of demographic characteristics and dimensions of chronic pain were calculated across those studies that provided information. Table 1 summarizes the multidimensional characteristics of chronic pain in adults with SCD that were evaluated across the 19 studies. Table 2 provides a detailed summary of each study. Table 3 summarizes the percentage of participants with chronic pain identified in each study and identified which studies included patients with acute, recurrent sickle cell crisis pain, and mixed pain. Table 4 summarizes the words used by participants to describe their pain. Table 5 summarizes common sites of chronic pain in adults with SCD. Table 6 summarizes the strategies used by participants to manage their pain. All of the studies in this literature review provided information on more than one dimension of chronic pain in adults with SCD.

Table 1.

Summary of the Multidimensional Characteristics of Chronic Pain that were Evaluated in Studies of Adults with Sickle Cell Disease

Author, Year	Occurrence	Episodes	Duration	Pattern	Quality	Location	Intensity	Aggravating Factors	Relieving Factors	Functional Status
Anie et al. (2002)		X	X			X	X			X
Ballas et al. (2006)	X	X				X	X			X
Bodhise et al. (2004)	X		X				X		X	X
Booker et al. (2006)		X		X	X	X	X		X	X
Dampier et al. (2002)	X	X	X	X	X	X	X		X	X
Dampier, Ely, et al. (2004)	X	X				X	X
Dampier, Setty, et al. (2004)		X	X	X		X	X
Franck et al. (2002)	X	X			X	X	X
Gil et al. (2004)	X		X				X	X	X	X
Harrison et al. (2005)							X		X	X
Hernigou et al. (2006)	X					X		X
McClish et al. (2005)		X				X	X	X		X
McClish et al. (2006)	X	X	X			X	X
Pells et al. (2005)							X	X		X
Platt et al. (1991)	X	X					X
Sadat-Ali (1993)	X	X		X	X	X	X	X	X	X
Smith et al. (2005)	X	X			X	X	X	X	X	X
Smith et al. (2008)	X	X					X
Williams & Moskowitz (2007)	X	X
% of Studies	68%	74%	32%	21%	26%	63%	89%	32%	36%	58%

Table 2.

Summary of the Findings from Studies of Chronic Pain in Adults with Sickle Cell Disease

Author/Year Study Purpose/Design	Sample Characteristics Variables and Instruments	Major Findings	Conclusions Study Limitations
Anie, Steptoe, & Bevan (2002) To examine the relationship between pain, coping, and QOL in adult patients with SCD and assess the influence of these factors on health service utilization. Cross sectional study	N = 96 Mean age: 30.1 ± 8.8 years 33% male, 67% female Race/Ethnicity: 52% African, 46% Caribbean, 2% from other areas SES: 68% single; 19% married; 13% unknown Hgb type: 69% SS, 21% SC, 10% Sβ Pain status and health service utilization: Pain Interview Psychological coping: Coping Strategies Questionnaire revised for SCD (CSQ-SCD) QOL: Medical Outcomes Survey Short Form 36 (SF-36)	Pain episodes: 8.11 ± 12.9 episodes in 12 months; Duration: 155 ± 156 hours Pain intensity: 7.5± 2.7; Bodily pain score on SF-36 = 52.0 ± 29.3 Relieving factors: fluids, rest, isolation, praying Functional status: Pain had negative effect on physical function and role limitations Occurrence, pattern, pain descriptors, location, aggravating factors: NR	Conclusions: Patients who reported greater use of active coping strategies experienced more episodes of pain. Patients who used passive coping strategies had higher pain intensity. Patients who reported greater coping strategies had poorer QOL. Pain experience accounted for 12.3% of hospital and general practice services. Psychological coping was unrelated to health service utilization. Limitations: No power analysis reported to justify the sample size Sickle cell pain not defined
Ballas et al. (2006) To investigate the effects of hydroxyurea on health related QOL (HQOL) measures in SS patients. RDBPCT study over a two year period	N = 299 (277 final analysis) Mean age: 33years 49% male, 51% female Race/Ethnicity: 95% Black SES: Almost all completed HS; 59% unemployed; marital status NR Hgb type: 100% SS Daily bodily pain: diaries of daily bodily pain Frequency of pain episodes: diaries of daily bodily pain HQOL: SF-36, Profile of Mood Status (POMS), Ladder of life	Occurrence: 44% reported daily chronic pain Pain episodes: 56% had ≥ 6 pain crisis annually. All had at least 3 pain crises/year. Hydroxyurea reduced the frequency of pain crises. Pain intensity: mean daily pain scores over four weeks pre-treatment 49% = 1to 3, 35% = 4 to 6, SF-36 bodily pain recall score = 46.5. Significant improvement in 4 week pain recall. Functional status: baseline daily pain was a significant independent predictor of several QOL outcomes at all time points Relieving factors: See pain intensity Duration, pattern, pain descriptors, location, aggravating factors: NR	Conclusions: Hydroxyurea improved certain aspects of QOL. Baseline daily pain was a significant predictor on many QOL measures. Although acute pain episodes were reduced, chronic daily pain continued to be high. Limitations: Source of chronic pain not reported
Bodhise, Dejoie, Brandon, Simpkins, & Ballas (2004) To evaluate whether deep tissue/deep pressure neuromuscular massage (NMT) reduces pain intensity and opioid consumption and increases relaxation and activities of daily living (ADL) in chronic pain experienced in SCD. Intervention study	N = 5 (4 adults & 1 child) with AVN and degenerative disease of the spine Mean age: 30 years (adults = 20–44 years, 1 child 12 years of age) 60% male, 40% female Race/Ethnicity: 100% African American SES: NR Hgb type: 40% SS, 40% SC, 20% Sβ Sickle cell pain: Numeric Pain Index (NPI) Typical coping response to stress, pain, changes in mood, expectation of pain management, and economic effect of pain and its treatment: Tension and Profile of Mood Scale (TPMS) ADL: Activities of Daily Living Assessment	Occurrence: 100% experienced chronic pain Pain intensity: Significant improvement after completion of therapy; pain scores 9.6 ± 0.80 before massage and 2.8 ± 0.75 after massage Aggravating factors: N/A Relieving factors: NMT Functional status: ADL 3.8 ± 0.4 before massage and 1.8 ± 0.75 after massage Pain episodes: NR Duration, pattern, location, pain descriptors: measured but NR	Conclusions: After NMT participants reported relief of pain and tension, a sense of relaxation, and improvement in their ADL that persisted for up to 24–48 hours post NMT. The need for analgesics was reduced for 24 hours in the majority of participants. Limitations: Dimensions of chronic pain measured but not reported Limitations not discussed No information provided on recruitment methods
Booker, Blethyn, Wright, & Greenfield (2006) To gain a greater understanding of SCD patients’ experience and views of pain management, access to treatment, and relationships with healthcare providers. Cross sectional study - Focus groups obtained through purposive sampling.	N = 20 selected, 10 responded. Mean age: 32 years 60% male, 40% female Race/Ethnicity: Afro-Caribbean, African, and Portuguese SES: 50% unemployed, 20% students, 10% employed P/T, 10% volunteer, 10% disabled; 70% single, 30% married Hgb type: NR Pain and pain management strategies: Focus groups using detailed personal interviews	Pain episodes: Mild crises managed at home, Medical help needed for severe crises Pattern: unexpected and rapid Pain descriptors: thousands or millions of needles pinching and jooking; pain comes in all different shapes and sizes. Location: joints and all over the body Pain intensity: on a continuum, ranging from mild to severe during a crisis. Relieving factors: faith and analgesics Functional status: themes: fear, socializing, coping Occurrence, duration, aggravating factors: NR	Conclusions: Patients with sickle cell pain do not feel that their pain is adequately managed by healthcare professionals owing in part to a lack of understanding by healthcare professionals. The impact of social isolation is underestimated in SCD. Limitations: Details on chronic pain not reported All participants were users of the resources at the Sickle Cell and Thalassaemia (SCAT) Center where the study took place Relationships of themes to pain dimensions were not specified Effectiveness of the medications was not reported
Dampier, Ely, Brodecki, & O’Neal (2002) To improve the understanding of sickle cell pain (SCP) and its management through the use of home diaries. Longitudinal study up to six months	N = 35 Mean age: 10.9 years (range – 6 to 19 years) 49% male, 51% female Race/Ethnicity: 91.4% African American SES: Not reported in this study, but study is part of a larger study in which the majority of the sample was unemployed. Hgb type: 72% SS SCP and other pain: Pain diaries included 0–10 VAS Pain descriptors: APPT Pain interventions for sickle cell pain: Pain diaries	Occurrence: 98% SCP alone; 97% other pain Pain episodes: see duration Duration: mean 3.6 days SCP; 3.5days SCP + other pain; 1.6 days other pain alone; range 1–78 days Pattern: no difference in pain at night and day Pain descriptors: ‘steady’ common for SCP/SCP + other pain; ‘comes and goes’ common for other pain Location: common sites = legs, right hip, lower back Pain intensity: Weighted mean = 5 SCP alone; mean = 7 SCP + other pain Relieving factors: analgesics and non-pharmacological methods Functional status: pain decreased usual daily activity Aggravating factors: NR	Conclusions: The use of a home diary was useful in understanding the characteristics of SCP and its management and may be useful as a primary outcome measure for therapeutic trials in SCD. Limitations: Definition for SCP narrow; only mentions the acute VOEs, but not chronic SCP Other pain not distinguished as acute or chronic
Dampier, Ely, Eggleston, Brodecki, & O’Neal (2004) To determine the pain management strategies used by children and adolescents, with SCD who manage their pain at home. Longitudinal study	N = 39 Mean age: 10.9 years (range 6 to 21 years) 49% male, 51% female Race/Ethnicity: 92% African American SES: NR Hgb type: 68% SS Pain: Pain diary	Occurrence: SCP reported on 14% of days and 13% of nights. Pain episodes: mean =11.9 ± 19.6 Pain intensity: 1–10 Relieving factors: sleeping, hot bath/heating pad, massage, and relaxing/meditation/self hypnosis. Cognitive behavioral and physical activities were used on 84.6% of days with SCP. Analgesic use with cognitive behavioral activities used on 77% of days. Analgesic used alone one 10.9% of days. Cognitive behavioral activities used alone on 7.5% of days. Combination of activities increased with increasing pain intensity Duration, pattern, pain descriptors, location, aggravating factors, functional status: NR	Conclusions: Cognitive behavioral and physical activities are used frequently for pain in SCD. Combination of activities increased with increasing pain intensity. Limitations: Effectiveness of cognitive behavioral and physical activities on pain not measured SCP used interchangeably with sickle cell pain episodes
Dampier, Setty, et al. (2004) To describe the characteristics of home managed painful episodes and to understand the vascular occlusion in SCD. Longitudinal study for up to 6 months	N = 30 Mean age: 10.6 years (range 6 to 21 years) 57% male, 43% female Race/Ethnicity: NR, but included Spanish speaking patients SES: NR Hgb type: 80% SS, 20% SC Pain: Pain diaries included 0–10 (VAS) validity reported Hematologic and biologic variables: Laboratory testing	Pain episodes: 8 episodes required hospital admission; 40% had at least 1 pain episode/month, 12% had > 2 episodes/month; total of 175 pain episodes Duration: 5% of home managed episodes lasted over 2 weeks Pattern: unexpected/rapid Location: females had greater number of painful sites Pain intensity: mild to moderate on most pain days. Severe pain ≥ 7 on 12% of pain days. Younger children reported less intense pain than adults. Relieving factors: increased HgF levels associated with longer duration between pain episodes Occurrence, pain descriptors, aggravating factors, functional status: NR	Conclusions: A direct relationship exists between vaso-occlusive pain and biomarkers. Vaso-occlusive pain can be experienced long after the initial tissue injury has ended. Limitations: Chronic and acute sickle cell pain not differentiated Specific pain locations not reported Small sample size limits generalizability
Franck, Treadwell, Jacob, & Vichinsky (2002) To describe the characteristics of pain experienced by children and young adults with sickle cell disease (SCD) and compare the pain experiences in inpatient and outpatient settings. Cross sectional study	N = 56 Mean age: 15.9 ± 4.32 years 46% male, 54% female Race/Ethnicity: African American SES: NR Hgb type: 84% SS, 9% SC, 7% Sβ Pain: APPT Pain measured with VAS 0–100mm	Occurrence: 23 clinic visits and 25 day hospital visits r/t pain episodes; 7 clinic visits r/t to pain associated with AVN Pain episodes: only reported on number of participants treated for pain episode Pain descriptors: used mostly evaluative words; females used more word descriptors Location: chest, upper and lower back, and legs; females reported more body areas Pain intensity: 5.92 ± 2.62 for clinic patients; 6.99 ± 1.56 for day hospital patients; females reported higher pain intensity Duration, pattern, aggravating factors, relieving factors, functional status: NR	Conclusions: Older children and young adults reported more body areas with pain (p < 0.001) and used more evaluative and temporal words to describe pain (p < .02, p < .04). Pain intensity, number of body areas with pain, and quality of pain were related to age, sex, and care setting. Limitations: Unknown if description of pain specific to pain episodes and/or chronic pain in SCD
Gil, Carson, Porter, Scipio, & Bediako (2004) To analyze daily patterns of pain, positive and negative affect, and stress in adults with SCD over several months. Longitudinal study up to 6 months	N = 41 Mean age: 36.6 years (range 18 to 71years) 44% male, 56% female Race/Ethnicity: African Americans SES: 34% less than HS, 56% HS and some college, 10% college degree; 71% disabled, 15% employed, 2% unemployed, 12% students; 56% never married, 22% married, 17% divorced, 5% widowed Hgb type: 80% SS, 15% SC, 5% Sβ SCD pain, other pain and health care use: Daily diary containing questions modified by the Structured Pain Interview and the Daily Self Monitoring Record; 100 mm VAS scale Stress: Daily Diary as above Mood: The Daily Mood Scale	Occurrence: SCD pain on 33% of diary days. Pain on 168 of 174 days Duration: Mean pain duration = 10.1 hours Pain intensity: mean = 53.5 on pain days Aggravating factors: stress, NA, physical exertion, and exposure to extreme temperatures Relieving factors: PA and fluid intake Functional status: ratings of SCD pain were significantly and positively associated with same day work absences Pain episodes, pattern, pain descriptors, location: not measured	Conclusions: Increased daily stress and NA were significantly associated with more SCD pain. PA and higher fluid intake were significantly associated with increased SCD pain Limitations: Small sample size Possible bidirectional effects of variables SCD pain not differentiated as chronic SCP or SCD pain crisis Mood was a confounding variable in work absence
Harrison et al. (2005) To examine the association among church attendance, prayer/Bible study, and intrinsic religiosity on measures of pain in adults with SCD. Cross sectional study	N = 50 Mean age: 36.7 years (range 18 to 70years) 44% male, 56% female Race/Ethnicity: 100% African American SES: 38% employed, 60% unemployed; 28% less than HS, 32% HS/GED, 20% some college, 2% Graduate school; 26% married, 50% single: 16% divorced, 4% living with a significant other, 2% separated Hgb type: 68% SS/Sβ°, 20% SC, 12% other Pain measures: McGill Pain Questionnaire Short Form (SF-MPQ), VAS (0–100mm) Religiosity: Duke Religious Index Psychological Distress: Symptom Checklist-90 Social desirability: Marlow Crowne Social Desirability Scale Disease severity: Combined measure using SCD and self-reported number of pain medications during pain episodes	Pain intensity: lower pain intensity on the VAS (p<.0004) and present pain (p < .0175) with church attendance Relieving factors: church attendance, prayer, Bible study Functional status: increased pain associated with higher scores on the Disease Severity Scale Occurrence, pain episodes, duration, pattern, pain descriptors, location, aggravating factors: NR	Conclusions: Participants who attended church reported lower pain intensity. Multiple regression analysis showed that church attendance was a significant predictor of the sensory, affective, and present experience of pain. Limitations: Participants unable to attend church related pain and/or physical disability not examined Small sample size Relationship between religiosity and pain unknown due to cross sectional design
Hernigou, Habibi, Bachir, & Galacteros (2006) To define the natural history of asymptomatic osteonecrosis of the femoral head in adults patients with SCD. Longitudinal study, 14 year follow-up	N = 121 Mean age: 26 years (range 18 to 31 years) 58% male, 42% female Race/Ethnicity: NR SES: NR Hgb type: 40% SS, 48% SC, 12% Sβ Extent of asymptomatic osteonecrosis: Steinberg classification system for grading osteonecrosis Harris Hip Score Clinical progression of osteonecrosis: Occurrence of pain	Occurrence: 91% of participants had pain, 75% had intractable pain requiring surgery. Location: hips Aggravating factors: progression of symptomatic osteonecrosis Relieving factors: hip replacement Pain episodes, duration, pattern, pain, descriptors, pain intensity, functional status: NR	Conclusions: The occurrence of pain was a significant predictor of collapse in the asymptomatic hip. Pain always preceded collapse of the hips. Time from pain symptom to collapse was 35 months. Limitations: Pain intensity not measured
McClish et al. (2005) To assess the health related quality of life (HRQOL) in adults with SCD and compare HRQOL in SCD to other chronic pain conditions. Longitudinal cohort study for up to 6 months	N = 308 Mean age: 33 years (range 16 to 64 years) 40% male, 60% female Race/Ethnicity: NR SES: 13% less than high school, 38% HS graduate, 36% some college, 13% college graduate; 22% married, 64% never married, 14% divorced, separated, widowed Hgb type: 67% SS, 24 % SC, 3% Sβ°, 3% Sβ+, 3% unknown HRQOL: SF-36 Sickle cell genotype: medical records Mean daily pain, percentage of self-reported crisis days, percentage of days with health service utilization: pain diary	Pain episodes: percentage of days with crisis was an independent predictor of bodily pain (p=.01) Location: on average 47% of patients reported bodily pain; women reported worse bodily pain Pain intensity: Mean daily pain was highly predictive of all subscales on SF-36 except mental health. Increased SCD pain associated with decreased QOL. SF-36 bodily pain score = 47.4. Aggravating factors: % of days with crisis Functional status: pain had a significant negative impact on physical and social functioning Occurrence, duration, pattern, pain, descriptors & relieving factors: NR	Conclusions: Participants scored lower than the national norm on all subscales of the SF-36 except mental health. HRQOL decreased significantly as pain increased. Limitations: Data on type of mean daily pain associated with SCD not provided Details on pain crisis not provided
McClish et al. (2006) To compare adult men and women with SCD in terms of reported pain, crises, healthcare utilization, and opioid usage. Longitudinal cohort study of up to 6 months duration	N = 308 enrolled; 226 completed study Mean age: 34 years (range 23 to 56 years) 38% male, 62% female Race/Ethnicity: NR SES: 12% less than HS, 38% HS graduate, 49% some college Hgb type: 69% SS, 24% SC, 2% Sβ°, 3% Sβ+ Pain measures: Daily diary including numerical rating scale (NRS) of 0–9 for variables measured HQOL: SF-36 Depression: PHQ	Occurrence: men = 58.6% pain days; women = 56.5% pain days Pain episodes: men with SS/Sβ° genotype experienced more pain crises than women with SS/Sβ°; women with SC/Sβ+ experienced more pain crises than men with SC/Sβ+ Duration: consecutive pain crisis days in 6 month period = 7.7 for men and 9.6 for women Location: bodily pain Pain intensity: during crisis mean pain intensity was 5.5 ± 1.9 for men; 5.6 ± 1.8 for women; mean non crisis pain intensity was 2.5 ± 2.4 for men and 2.2 ± 2.0 for women Pattern, pain descriptors, aggravating factors, relieving factors, functional status: NR	Conclusions: Women reported worse bodily pain than men. Men and women differed in the frequency of pain crises depending on SCD genotype. Limitations: SF-36 not specific to SCP Pain used interchangeably with SCP and pain crisis Unclear if participants experienced chronic pain in addition to frequently occurring acute pain Details regarding pain descriptors used by men and women with SCD not reported
Pells et al. (2005) To explore the relationship between pain severity and BMI in adult patients with SCD. Cross-sectional survey design and medical record review	N = 62 Mean Age: 37 years for adult patients 53% male, 47% female Race/Ethnicity: NR SES: NR Hgb type: NR Pain: LEMPFSCD Diet/Nutritional Intake: LEMPFSCD Psychological distress: LEMPFSCD	Pain intensity: moderate pain levels of 5.6 resulted in altered eating patterns Aggravating factors: perceived current weight Relieving factors: not measured Functional status: 87% of patients reported that they ate less during episodes of chronic pain Occurrence, pain episodes, duration, pattern, pain descriptors, location: not measured	Conclusions: Weight had a greater impact on functional ability associated with pain than pain severity. Limitations: Retrospective recall of information Unclear if SCD pain versus general pain measured Pain episode not defined although appeared to refer to chronic pain episode
Platt et. al (1991) To study the natural history of sickle cell disease and to understand the characteristics of SCP in individuals with SCD. Longitudinal study	N = 3578 Mean age: 35% greater than 20 years (range newborn to 66 years) % of males and females: NR Race/Ethnicity: Black SES: Median income $8900 20% of adults 25 to 59 years were unemployed or disabled; 58% were employed Marital status only provided for 35 to 44 year olds Hgb type: 67% SS, 23% SC, 5% Sβ+ 5% Sβ° Pain rates: medical records, not clear how pain was measured Pain episodes: medical records, not clear how episodes were rated Health service utilization: medical records, HbF levels	Occurrence: Pain rate of episodes higher for 25–34 year olds Pain episodes: 32.9% had 3 to 10 episodes per year Pain intensity: patients over 20 years of age with higher pain intensity had more pain episodes and tended to die earlier than those with low rates Duration, pattern, pain descriptors, location, aggravating factors, relieving factors, functional status: NR	Conclusions: SCP is associated with high mortality in adults over 20 years of age with more than 3 episodes per year. Limitations: Participants with hemoglobin of greater than 7 were excluded from the study, even if they could have had sickle cell pain Not clear how pain was measured
Sadat-Ali (1993) To classify the stages of avascular necrosis of the femoral head (ANFH) in SCD. Longitudinal study	N = 43 Mean Age: 15.5 years (7 to 44 years) 47% male, 53% female Race/Ethnicity: 100% Saudi Arabian SES: NR Hgb type: 100% SC ANFH: Classification system using integrated factors of patient’s history, clinical findings, and radiologic picture	Occurrence: 100% had AFNH and experienced some form of pain. Pain episodes: chronic pain Pattern: pain severity worse with Grade progression Pain descriptors: Grade I vague pain; Grade II constant pain; Grade III moderate to severe; Grade IV severe to unbearable Location: hips, groin, back Pain intensity: vague to unbearable Aggravating factors: flexion, abduction, adduction Relieving factors: Grade II required analgesics; Grade IV required surgical intervention to relieve pain and increase mobility. Functional status: physical activity limited and decreased mobility Duration: NR	Conclusions: Early diagnosis of AFNH is needed to avoid complications associated with the disease. AFNH divided into 4 Grades with the patient experiencing progressively worse pain and functional limitations with each increase in grade. Limitations: No measurement tool for pain reported Duration of pain not reported
Smith, Coyne, Smith, Roberts, & Smith (2005) To test the effects of an intrathecal drug delivery systems (IDDS) for refractory chronic bone pain associated with SCD. Cross sectional, case study	N = 2 Mean Age: Case 1 = 52 years of age; Case 2 = 27 years of age Both female Race/Ethnicity: NR SES: NR Hgb type: 100% SC Chronic sickle cell anemia bone pain: VAS	Occurrence: Frequent Pain episodes: Case 2 averaged 6–7 hospital admissions for pain crisis per year, sometimes as many as every 2–3 weeks. Pain descriptors: severe Location: chronic bone pain multiple bones; shoulder and hips Pain intensity: Case 1=10/10 Case 2=7/10 at rest; 10/10 with ambulation. Aggravating factors: ambulation; Relieving factors: analgesics for breakthrough pain; Case 1= IDDS of 13.2 mg of morphine per day. Case 2 = 5.8mg of hydromorphone per day Functional status: decreased physical activity and mobility Duration, pattern: NR	Conclusions: An IDDS reduced refractory chronic bone pain and improved normal activity in two adults with SCD. More research is warranted on the use of IDDS for chronic pain in adults with SCD. Limitations: Impact of acute sickle cell pain episodes on chronic pain not measured or reported Limited information on quality of pain. No information on duration or pattern of pain
Smith et al. (2008) To examine the prevalence of self-reported pain and the relationship among pain crises and utilization in adults with SCD. Longitudinal prospective cohort study (6 months)	N = 232 Mean Age: 16 to 64 years 62% male, 38% female Race/Ethnicity: NR SES: 12% less than HS, 38% HS graduate, 35% some college, 15% college graduate; 24% married, 62% never married, 14% divorced, separated, widowed; Majority income less than $10, 000 Hgb type: 73% SS/ Sβ°, 27% SC/ Sβ+ Self reported pain, crisis, and health care utilization: daily diary	Occurrence: 29% had chronic pain (pain nearly every day of study period) Pain episodes: patients did not seek treatment for pain crises on 13% of days Pain intensity: Mean pain intensity without crisis = 4; crisis without utilization = 5; health care utilization with or without crisis = 6. Mean pain intensity increased as number of pain days increased Duration, pattern, pain descriptors, location, aggravating factors, relieving factors, functional status: not measured	Conclusions: Adults with SCD experience pain more frequently than previously reported. Healthcare providers should trust reports of pain in patients with SCD and give attention to outpatient treatment, as well as inpatient treatment. More than half of patients (54%) reported pain on more than half of the days. Limitations: Pain variable not defined SCD pain not differentiated from other types of pain
Williams & Moskowitz (2007) To investigate the effects of Trandoloapril on pain in SCD. Longitudinal case study	N = 1 Mean Age: 48 year old female Race/Ethnicity: African American SES: NR Hgb type: SS Pain - No information on pain measurement	Occurrence: daily pain episodes for as long as patient could remember Pain episodes: 3–4 episodes per year Pattern: worse during winter months Pain descriptors: severe Location: joint pain in the elbows, hips, and knees Aggravating factors: frequency and severity of pain episodes worsened during winter months Relieving factors: pain episodes treated with fluids, analgesics, and occasional blood transfusions. Joint pain treated with 2–6 hydrocodone and acetominophen tablets per day and hot baths. Pain intensity, duration, functional status: NR	Conclusions: Trandolapril 1mg per day reduced patient’s pain and the need for other analgesics for greater than 12 months. ACE inhibitors may play a role in pain management in adults with SCD. Limitations: Limited information on characteristics of acute pain and chronic joint pain Effect of pain on functional status not reported

Abbreviations: ACE - angiotensin 1-converting enzyme, AFNH – avascular necrosis of the femoral head, APPT – Adolescent Pediatric Pain Tool, AVN – avascular necrosis, BMI – Basal Metabolic Index, GED – General Education Development certificate, HbF – fetal hemoglobin, HQ – Patient Health Questionnaire, HS – high school, LEMPSCD - Longitudinal Exploration of Medical and Psychosocial Factors in SCD, NA – negative affect, NR – not reported, PA – positive affect, P/T – part time, QOL – quality of life, RDBPCT – Randomized Double Blind Placebo Controlled Trial, r/t – Related to, Sbeta zero (Sβ° ) – sickle beta zero thalassemia, Sbeta plus (Sβ⁺) – sickle beta plus thalassemia, SC – one sickle hemoglobin gene and one abnormal hemoglobin ‘C’gene, SCD – Sickle Cell Disease, SCP – sickle cell pain, SS – two sickle hemoglobin genes (Sickle Cell Anemia), VAS – Visual Analog Scale

Table 3.

Various Types of Pain that were Evaluated in Studies on the Prevalence/Incidence of Chronic Pain in Adults with Sickle Cell Disease

Author, Year	Sample Size	Chronic Pain	Recurring Acute Pain Crises	Mixed Pain (% Chronic Pain)
Anie et al. (2002)	96		X
Ballas et al. (2006)	299			X
Bodhise et al. (2004)	5	X (100%)
Booker et al. (2006)	10		X
Dampier et al. (2002)	35			X
Dampier, Ely et al. (2004)	39			X
Dampier, Setty, et al. (2004)	30		X
Franck et al. (2002)	56	X	X
Gil et al. (2004)	41			X
Harrison et al. (2005)	50		X
Hernigou et al. (2006)	121	X (100%)
McClish et al. (2005)	308			X
McClish et al. (2006)	226			X
Pells et al. (2005)	62	X (100%)
Platt et al. (1991)	3578		X
Sadat-Ali (1993)	43	X (100%)
Smith et al. (2005)	2			X (100%)
Smith et al. (2008)	232			X (29%)
Williams & Moskowitz (2007)	1			X (100%)
Total Number of Studies from 19	5234	5	6	9

Note: Percentages for participants with chronic pain given only for those studies providing details on this information

Table 4.

Pain Descriptors Used for Chronic Pain in Adults with Sickle Cell Disease

Descriptor	Booker et al., 2006	Dampier et al., 2002	Franck et al., 2002	Sadat-Ali, 1993	Type of Chronic Pain
Aching			X		Chronic, Recurring Acute, Mixed
Awful		X	X		Chronic, Recurring Acute
Annoying			X		Chronic, Recurring Acute
Bad			X		Chronic, Recurring Acute
Comes all of a sudden	X	X	X		Chronic, Recurring Acute, Mixed
Comes and goes		X	X		Chronic, Recurring Acute, Mixed
Comes in all different shapes and sizes	X				Recurring Acute
Comes on slowly		X			Mixed
Constant			X	X	Chronic, Recurring Acute
Continuous			X		Chronic, Recurring Acute
Crying			X		Chronic, Recurring Acute
Dizzy			X		Chronic, Recurring Acute
Frightening		X			Mixed
Hurting			X		Chronic, Recurring Acute
Jooking!	X				Recurring Acute
Miserable		X	X		Chronic, Recurring Acute, Mixed
Off and on			X		Chronic, Recurring Acute
Pressure			X		Chronic, Recurring Acute
Severe				X	Chronic
Sneaks up			X		Chronic, Recurring Acute
Steady		X	X		Chronic, Recurring Acute, Mixed
Throbbing			X		Chronic, Recurring Acute
Thousands or millions of needles pinching you	X				Recurring Acute
Tingling	X				Recurring Acute
Unbearable		X			Mixed
Uncomfortable		X	X		Chronic, Recurring Acute, Mixed
Unexpected	X				Recurring Acute
Vague				X	Chronic
Total number of descriptors from 28	6	9	18	8

Table 5.

Common Sites of Chronic Pain in Adults with Sickle Cell Disease

Location	Bodhise et al., 2004	Booker et al., 2006	Dampier et al. 2002	Dampier et al., 2004	Franck et al., 2002	Hernigou et al., 2006	Sadat-Ali 1993	Smith et al., 2005	Williams & Moskowitz, 2007
Abdomen					19%
All over body		10%
Arm					7%
Back	60%		X	X	99%		23%
Chest				X	81%
Elbow joints									100%
Groin							30%
Hips	60%		X	X		100%	70%		100%
Legs			X	X	90%
All joints		10%
Knee joints									100%
Shoulder	20%
Multiple bones/ areas	40%	10%	X	X	5%		23%	100%	100%

Total of 13 sites

Note: Weighted means for back pain (60%), hip pain (80%), and multiple bones/areas (14%)

Table 6.

Strategies Used to Relieve Chronic Pain in Adults with Sickle Cell Disease

Strategy	Anie et al., 2002	Bodhise et al., 2004	Booker et al., 2006	Dampier et al.,2002 2004a 2004b	Gil et al., 2004	Harrison et al., 2005	Hernigou et al., 2006	McClish et al., 2006	Sadat-Ali, 1993	Smith et al., 2005	Smith et al., 2008	Williams & Moskowitz, 2007
Analgesics	X		X	X (a,b)				X	X	X	X	X
Bible Study						X
Calming Statements	X
Church attendance						X
Cold	X
Communication				X (a)
Faith/ Hoping	X		X
Fluids	X				X							X
Heat	X			X (a)
Hot bath				X (a)
Isolation	X
Increasing activity	X
Massage		X		X (a)
Meditation				X (a)
Positive mood					X
Praying	X			X (a)		X
Reading				X (a)
Relaxation	X			X (a)
Self-hypnosis				X (a)
Sleep				X (a)
Surgery							X		X
Watch TV				X (a)
Total number of studies = 22	10	1	2	1 (b) 24 (2002a)	2	3	1	1	2	1	1	2

Summary of the Design and Methods Used in Studies of Chronic Pain in Adults with SCD

Seven cross sectional studies (10, 18, 19, 23, 25, 29, 31) and 12 longitudinal studies (8, 17, 20–22, 24, 26–28, 30, 32, 33) have investigated chronic pain in adults with SCD. Three studies evaluated interventions for pain (18, 31, 33). Only one study used qualitative methods (19).

The sample sizes in these studies ranged from 1 to 3578 (total number of participants = 5234). Nine studies (47%) had samples of less than 50 (Table 1). Two of them were case studies of patients with chronic pain caused by avascular necrosis of the hips and shoulder (30, 32).

All 19 studies provided some information on the demographic characteristics of the participants. However, only nine (47%) provided details on socioeconomic status. Approximately half of the studies (47%) included both children and adults (8, 18, 20–23, 27, 30, 32). Across the 19 studies, slightly more females participated than males (females = 2761, 53%; males = 2473, 47%). The adults ranged from 18 years to 71 years (mean age = 32.6 years). An attempt was made to calculate the percentage of adults who reported on particular demographic characteristics (i.e. educational level, employment, marital status, hemoglobin type), but due to the inclusion of children in some of the studies and data reported inconsistently, calculations of weighted means/proportions were done for those studies with only adult participants.

In three of the 19 studies (24, 25, 28), approximately 82% of the participants were high school graduates, had some college, or a college degree. Approximately 17% of the participants had not completed high school. In the four studies that reported on employment (17, 19, 24, 25), most of the participants (61%) were unemployed and/or disabled. In four of the 19 studies that reported on marital status (10, 19, 24, 25), 72% of the participants were unmarried or separated. Only two studies (8, 32) reported on the annual income of the participants. In one study (8), 57% of the participants reported an annual income of < $10,000. In the second study (32), 39% of the participants reported an annual income of < $10,000. In four studies (10, 24, 26, 28), approximately 63% of the participants had hemoglobin (Hb) type SS (the most common genotype in SCD, and along with Hb Sβ° thalassemia, the more severe form of the disease), approximately 29% had Hb SC (the second most common genotype in SCD), and 8% had Hb Sβ (Sβ⁺ thalassemia or Sβ° thalassemia).

Six studies (10, 17, 19, 24, 25, 33) reported on the race/ethnicity of the participants. In four of these studies (17, 24, 25, 33), approximately 96% of study participants were African American and/or Black. In three studies (24, 25, 33), all of the participants were African American. In one study (10), all of the participants were African and Caribbean. In another study (19), participants were African, Afro-Caribbean, and Portuguese.

Several instruments were used to measure chronic pain and quality of life (QOL). In eight studies (17, 20–22, 24, 27, 28, 32), daily pain diaries obtained information on the presence or absence of sickle and non-sickle related pain, pain intensity, pain location, pain descriptors, precipitants of sickle pain, pain relieving techniques, actual or potential stressors, healthcare use, and limitations in physical and social activities. One study (25) used the McGill Pain Questionnaire. In another study (29), the Multidimensional Pain Inventory (MPI-2), a short form of the West Haven-Yale Multidimensional Pain Inventory (WHYMPI), was used to assess pain. Six studies used a visual analog scale (VAS) to assess pain intensity (20, 22–25, 31). Four studies (10, 17, 27, 28) used the Medical Outcome Study 36-item Short Form (SF-36) to measure bodily pain and QOL. Pain interviews were done in three studies (10, 19, 24). Two studies did not report which instruments were used to measure pain (26, 33). Validity and reliability of all of the instruments were reported or referenced.

Fourteen of the 19 studies listed exclusion criteria. In three studies (25, 29, 32), participants were excluded if they were having a pain crisis or other urgent medical conditions at the time of the clinic visit. In three studies (10, 22, 32), participants who could not read, write, and comprehend English were excluded. In two studies (21, 22), participants were excluded if they received chronic transfusions or hydroxyurea. The main reason participants refused to participate or withdrew from these studies was time constraints.

In terms of the types of chronic pain that were evaluated, five studies (18, 23, 26, 29, 30) analyzed a number of dimensions of chronic pain in adults with SCD. Six studies (8, 10, 19, 22, 23, 25) analyzed recurring episodes of acute pain crises, a common cause of chronic pain in adults with SCD. Nine studies (17, 20, 21, 24, 27, 28, 31–33) included participants with multiple types of pain (e.g., acute pain superimposed on chronic pain). The majority of the studies that evaluated multiple types of pain did not provide detailed information on the specific etiology of the chronic pain.

None of the studies in this review defined chronic pain. However, three studies provided a definition for SCP (20, 22, 23). In two studies (20, 22), this was defined as vaso-occlusive episodes typically experienced by patients with SCD. In another study (23), SCP was defined as acute and chronic pain that varied in intensity, location, quality, and temporal pattern. Three studies (21, 28, 32) defined sickle crises. In one study (21), sickle cell crisis was defined as an unpredictable recurrent episode of pain from vaso-occlusion. In another study (28), crises were referred to as acute episodes of ischemic pain thought to be due to vaso-occlusion. In another study (32), crises were self-defined by each patient.

Across these 19 studies, pain was often used interchangeably with sickle cell pain, which made it difficult to distinguish whether the pain experience was caused by chronic pain, a vaso-occlusive episode, mixed pain, or pain unrelated to SCD. When pain was measured, it was not clear whether SCD pain versus pain unrelated to SCD was measured. In addition, no consistent definition for a pain episode was used across all seven studies that provided a definition. In some studies, an episode of pain was defined broadly, while in others it was defined as an acute pain crisis (20–24, 27, 32). Only three studies (20, 24, 32) differentiated SCD pain from other types of pain, but it was not clear whether the SCD pain or other pain was acute or chronic. Also, it was not clear whether SCD pain versus pain unrelated to SCD was measured.

Summary of the Pain Dimensions Evaluated Across Studies of Chronic Pain in Adults with SCD

Chronic pain in SCD can be due to many factors. The most common causes are recurrent pain episodes due to vaso-occlusion of the microcirculation and destruction of bones, joints, and visceral organs (11). Chronic pain in adults with SCD is a multifaceted experience that involves sensations, emotions, cognitions, memories, and context. Therefore, chronic pain must be assessed and managed from a multidimensional perspective (11, 34).

Pain Occurrence

Pain occurrence refers to the frequency with which an individual experiences pain in a given period of time or the incidence of a particular type of pain in a given population. Both of these definitions are needed to characterize the magnitude of the chronic pain experience of adults with SCD.

In the 11 studies that reported on pain occurrence (8, 17, 18, 20, 24, 26, 28, 30–33), participants reported experiencing chronic pain on 13% to 50% of study days. The percentage of participants with chronic pain varied from 29% to 100% across seven studies with a weighted mean of 65% (18, 26, 29, 30–33).

Pain Episodes

Chronic pain in adults with SCD can include superimposed acute sickle cell pain with accompanying vaso-occlusive episodes/pain crisis, and/or pain of multiple etiologies. A painful episode, which is caused by ischemic tissue injury that results from occlusion of the micro-circulation by sickled red blood cells, is the most common symptom of SCD. Furthermore, the frequent episodes of acute pain in SCD can resemble chronic pain (11).

The number of vaso-occlusive episodes was reported in nine studies (8, 10, 17, 21, 22, 28, 31–33). The majority of the participants had at least one painful vaso-occlusive episode per year, with some participants having as many as 24 vaso-occlusive episodes per year. The weighted mean number of vaso-occlusive painful episodes across the nine studies was 1.3 annually.

Duration

Six studies (10, 18, 20, 22, 24, 28) assessed the duration of pain in adults with acute sickle cell pain crisis and/or multiple pains from SCD. The mean duration of pain was variable, ranging from 10.1 hours to 9.6 days. Women reported pain episodes of longer duration than men. Increased fetal hemoglobin levels were associated with longer duration between pain episodes (22).

Pattern

For treatment purposes, it is important to determine the regularity of chronic pain and whether or not the pain is worse at a particular time of the day or night. Seven studies reported on the pattern of pain in adults with SCD (19, 20, 22, 23, 26, 30, 33). In three studies (19, 22, 23), the pain came on rapidly/suddenly and unexpectedly. These data are consistent with previous studies on the pattern of pain in acute sickle cell vaso-occlusive episodes (11, 35).

Quality

In the four studies that reported on pain qualities (19, 20, 23, 30), 28 pain descriptors were listed (Table 4). Some of the most commonly used words to describe pain were: awful, comes on all of a sudden, comes on slowly, severe, steady, uncomfortable, unbearable, and vague.

Location

In the nine studies that reported on the location of chronic pain in adults with SCD (18– 20, 22, 23, 26, 30, 31, 33), the hips were the most common pain site, followed by the back (Table 5). The percentage of participants with hip pain ranged from 60% to 100% (weighted mean = 81%) (18, 26, 30, 33). The percentage of participants with back pain ranged from 23% to 99% (weighted mean = 60%) (18, 23, 30). The percentage of participants with pain in multiple bones and/or areas simultaneously ranged from 5% to 100% (weighted mean = 14%) (18, 19, 23, 30, 31, 33). In two studies (22, 23), females reported more painful sites than males.

Intensity

Pain intensity was measured in 12 studies (10, 17, 18, 20, 22–24, 27–29, 31, 32). In eight studies (10, 18, 20, 22, 28, 29, 31, 32), mean pain intensity scores ranged from approximately 3.5 to 10 on a 0 to 10 VAS. The weighted mean across these eight studies was 5.3. In four studies (10, 17, 24, 27), the bodily pain score on the SF-36 ranged from 46.5 to 52 on a 0 to 100 scale. The weighted mean pain intensity score across these four studies was 48, which was significantly (P < 0.0001) lower than national norms and cohorts with other chronic pain conditions (i.e., hemodialysis, cystic fibrosis, asthma). In one study (31), mean pain intensity increased as the number of pain days increased. In three studies (23, 31, 32), females reported higher pain intensity scores than males. However, in another study (10), no differences in pain intensity scores were found between women and men.

Aggravating Factors

Six studies reported on the aggravating factors associated with chronic pain in adults with SCD (24, 26, 27, 29–31). Stress, negative affect, physical exertion, exposure to extreme temperatures, and the number of sickle cell episodes were significantly associated with increased SCD pain. In one study (24), negative affect was higher on pain days (mean=7.9) compared to nonpain days (mean=3.6). In this study, higher levels of physical exertion were associated with higher levels of pain (P < 0.001) and increased stress was associated with increases in same day pain (P < 0.001). In another study (27), the percentage of days with sickle cell crisis was an independent predictor of bodily pain. As the proportion of days with crisis increased, so did pain.

Relieving Factors

Fourteen studies reported on factors that relieved chronic pain in persons with SCD (10, 18–22, 24–27, 30–33). Overall, 23 pain management strategies were reported (Table 6). In ten studies (67%) (10, 19–22, 28, 30–33), analgesic administration was the most common strategy used to manage chronic pain. The majority of the patients used analgesics either alone or in combination with nonpharmacologic methods.

Seven studies reported on the use of nonpharmacologic measures for chronic pain in adults with SCD (10, 18, 19, 20, 21, 25, 33). Four studies reported on the use of prayer (10, 20, 21, 25). In one study (18), participants reported significant decreases in pain intensity following massage (i.e., 9.6 ± 0.80 before massage and 2.8 ± 0.75 after massage). In another study (21), when analgesics were used along with nonpharmacologic measures, watching television or reading a book was the primary method of relieving pain, followed by talking with people. In a third study (25), participants who attended church one or more times per week reported lower overall pain intensity scores (P < 0.0004).

Functional Status

In the 11 studies that reported on the effects of chronic pain on the functional status of adults with SCD (10, 17–20, 24, 25, 27, 29, 30, 31), chronic pain had significant negative effects on participants’ QOL. In three studies (10, 17, 27), acute recurring vaso-occlusive episodes and mixed pain had a significant negative impact on participants’ physical and social functioning. In another study (17), baseline daily pain intensity was a significant predictor of decrements in the following QOL outcomes: general health now, social functioning, role limitations due to physical and emotional health, mental health, energy, fatigue, pain recall, tension-anxiety, depression-dejection, and ladder of life (participants own rating of their QOL). In one study (24), participants with more severe pain had increased work absences. Participants in another study (19) had recurrent themes of fear, death, uselessness, helplessness, loss of virility, and worsening ill health associated with increased pain.

Conclusions and Recommendations for Future Research

Because of advances in treatment, persons with SCD are living longer, which means that more adults are experiencing chronic pain associated with their disease. Findings from this review suggest that significant gaps exist in our knowledge of the multiple dimensions of chronic pain in this population. To date, no studies have examined in a comprehensive manner the multiple dimensions of the chronic pain experience of adults with SCD. A critique of the 19 studies done to date reveals some limitations.

First, studies that focused only on adults with SCD who experience chronic pain are extremely limited. Findings from this review suggest that chronic pain occurs in at least 29% of adults with SCD and most frequently in those 25 to 44 years of age. However, almost 50% of the studies reviewed included both children and adults, which makes it difficult to accurately assess the magnitude of the problem in adults. If children are included in studies of chronic pain in adults with SCD, and data are not reported separately for adults, one cannot determine the impact of chronic pain in adults. Studies are needed that focus specifically on adults with chronic pain from SCD.

Second, most of the studies on chronic pain in adults with SCD investigated recurring acute vaso-occlusive pain episodes and pain intensity related to these episodes. Only a few studies examined other dimensions of chronic pain or chronic pain due to other causes. Chronic pain in adults can occur from complications of SCD, such as avascular necrosis, ankle ulcers, or acute pain superimposed on chronic pain. Studies are needed that examine the multiple causes of chronic pain in this population.

Third, only 47% of the studies provided details on both demographic characteristics and socioeconomic status. Some of these studies provided only partial details and income was evaluated in only two studies. Chronic pain in adults with SCD is a multi-factorial experience which negatively impacts many areas of the individual’s QOL (e.g., family responsibilities, employment status). In order to better understand the association between demographic characteristics and socioeconomic status and chronic pain in adults with SCD, studies are needed which include more specific information on socioeconomic status.

Fourth, almost half of the studies in this review involved relatively small samples. Some of the potential problems associated with small sample sizes are low statistical power and the potential for Type II error. When consideration is given to the economic burden of treating chronic pain in adults with SCD, future research studies should include larger sample sizes that represent the breadth and depth of chronic pain in adults with SCD.

Fifth, some of the studies included in this review reported data from subsets of patients from the same sample. While each of these studies reported unique information that adds to the body of research on chronic pain in adults with SCD, the summaries provided in this review may overestimate some of the findings.

Lastly, none of the studies in this literature review defined chronic pain. In addition, it was difficult to distinguish whether the pain reported and measured was acute or chronic pain. While it is known that recurrent vaso-occlusive painful crises may be considered chronic pain in persons with SCD, it is not clear what determinants of the vaso-occlusive pain episodes constitute chronic pain in this population. Future studies on chronic pain in adults with SCD should specify criteria for a definition of chronic pain in SCD that is inclusive of the recurrent vaso-occlusive painful crises within the classification of chronic pain described for this population. Furthermore, future studies should include only those participants who meet the inclusion criteria set forth in that definition. It is necessary to have a definition of chronic pain in SCD to help guide treatment and improve pain management for individuals with this disabling condition.