Abstract
Almost half of sickle cell disease (SCD) patients develop chronic, debilitating physical pain with uncertain genesis for which they primarily receive opiate-based palliative treatment. Psychological trauma exposure, especially interpersonal victimization, has been linked to the perception of pain in several medical diseases, but has yet to be examined in SCD patients. This study examines self-reported chronicity of pain and use of prescribed opiates in 50 adult SCD patients with and without a history of interpersonal violence exposure. We conducted a retrospective chart review of 50 consecutive SCD patients seen for medical care in an adult subspecialty hematology clinic. Data collected included demographics, opiate use, pain chronicity, and measures of anxiety, depression, and interpersonal violence exposure. Sixty-eight percent of patients reported past interpersonal violence exposure. The mean number of types of interpersonal violence exposure, including physical, sexual, or emotional abuse, was 2.76 (SD = 1.63). SCD patients with a history of interpersonal violence exposure were almost five times more likely to report chronic pain and more than six times more likely to report use of opiate-based medications on a daily basis compared with SCD patients with no history of violence exposure. Depression and anxiety symptoms were associated with violence exposure, but did not account for the relationship between violence exposure and chronic pain or prescribed opiate use. Screening and assessment of exposure to interpersonal violence may be useful in addition to screening for mental health problems in the management of chronic pain with adults diagnosed with SCD. Such screening may contribute to addressing health care disparities given the preponderance of SCD patients who are of African American ethnoracial background.
Sickle cell disease (SCD), the most common genetic disorder of the blood, afflicts approximately 1 in 500 African Americans. In this lifelong condition, a single point mutation causes hemoglobin-containing red blood cells to form an irregular “sickled” shape. Sickled cells occlude small blood vessels and disrupt oxygen supply to body tissues, causing intense acute pain, organ dysfunction, and early mortality (Edwards et al., 2005; Platt, 2008). These acute vaso-occlusive pain episodes are the hallmark of SCD and the primary cause of hospitalizations (Ballas, Gupta, & Adams-Graves, 2012). However, nearly half of adults with SCD develop a chronic pain disorder (Ballas et al., 2012). The mainstay of therapy for both acute and chronic SCD-related pain is opiate based, yet such treatment is purely palliative, as targeted anti-vaso-occlusive pharmacotherapy is not available. Although the genesis of acute painful episodes in SCD is attributed primarily to intermittent blood vessel obstruction by deformed red blood cells, the etiology of transformation to chronic pain is thought to be biologically distinct and at least in part related to alterations in pain processing (Darbari, Ballas, & Clauw, 2014).
Health providers have speculated that stress from daily events can lead to the onset of painful episodes in SCD (Gil et al., 2004). Although research on the impact of exposure to stressors in SCD is limited, one study reported that 50% of patients endorsed having pain episodes preceded by stressful life events (Porter, Gil, Carson, Anthony, & Ready, 2000). Studies in SCD have demonstrated that stressful experiences and stress reactions (e.g., anxiety, depression) are positively associated with average pain intensity, health care use, work absences, and reduction in household and social activities (Gil et al., 2004; Porter et al., 2000; Porter et al., 1998; Tsao, Jacob, Seidman, Lewis, & Zeltzer, 2014).
Interpersonal violence exposure is a severe and potentially traumatic form of stressor exposure that can include witnessing or experiencing threatened or actual physical or sexual assault or emotional abuse. Exposure to traumatic interpersonal violence and persistent posttraumatic stress reactions have been linked to a plethora of physical and mental health problems including chronic pain (Bonomi et al., 2009; Campbell, 2002; Coker, Smith, Bethea, King, & McKeown, 2000; Nicolaidis, Curry, McFarland, & Gerrity, 2004), dysregulated stress response (Anda et al., 2006; Davies, Sturge-Apple, Cicchetti, & Cummings, 2008; Horan & Widom, 2015; Shenk, Noll, Putnam, & Trickett, 2010), as well as compromised immunological and metabolic functioning and physical health (Goldsmith, Freyd, & DePrince, 2012; Jun et al., 2012; Kendall-Tackett, 2013; Mackelprang et al., 2014; Schnurr & Green, 2004; Sumner et al., 2015). Posttraumatic stress symptoms and related psychosocial impairment have been shown to exacerbate pain and physical symptoms secondary to childhood abuse (Hart-Johnson & Green, 2012; Paras et al., 2009), severe injury (Beck, Gudmundsdottir, & Shipherd, 2003; Jenewein, Wittmann, Moergeli, Creutzig, & Schnyder, 2009), and illness (Smith, Egert, Winkel, & Jacobson, 2002), and to mediate the relationship between trauma exposure and pain (Powers et al., 2014).
Posttraumatic stress disorder (PTSD) also has been found to be linked to chronic pain by increased levels of depression (Feldman, Ortega, Koinis-Mitchell, Kuo, & Canino, 2010; Means-Christensen, Roy-Byrne, Sherbourne, Craske, & Stein, 2008; Morasco et al., 2013; Peterlin, Tietjen, Meng, Lidicker, & Bigal, 2008; Quarantini et al., 2009; Roth, Geisser, & Bates, 2008) and anxiety (Asmundson & Katz, 2009; Cougle, Feldner, Keough, Hawkins, & Fitch, 2010; Means-Christensen et al., 2008; Pao & Bosk, 2011). Furthermore, the combination of anxiety, depression, and chronic pain has been estimated to lead to high levels of social and economic costs as well as to high utilization of health care services (Zhu, Zhao, Ye, Marciniak, & Swindle, 2009). Exposure to traumatic stressors (Irish, Kobayashi, & Delahanty, 2010; Lawson, Back, Hartwell, Moran-Santa Maria, & Brady, 2013), including interpersonal violence (Strigo et al., 2010; Wuest et al., 2008), also has been found to be associated with opiate use in patients with chronic pain disorders.
Despite substantial evidence of a linkage between interpersonal violence exposure and persistent problems with depression, anxiety, chronic pain, and prescription opiate use, these relationships have not been empirically examined in adults with SCD. The current study, therefore, was designed as a case series investigation of the associations between violence exposure, depression and anxiety, chronic pain, and prescription opioid use in SCD patients. Given the preponderance of SCD patients who are of African American ethnoracial background, examining the relationship of interpersonal violence exposure to chronic pain in this population will help to increase the diversity of research findings regarding these important phenomena, and potentially to assist in efforts to reduce health care disparities for under-served adults of color.
Based on the extant research, the study tested the following hypotheses.
Method
Setting, Procedure, and Sample
The University of Connecticut Health Center’s (UConn Health) adult comprehensive SCD program has been in operation since 2009. The program cares for ~200 adults, and is staffed by a hematologist, a nurse practitioner, a registered nurse, a licensed clinical social worker, and a community liaison. During comprehensive visits, patients undergo a full medical evaluation and participate in the development of a comprehensive treatment plan. In addition, each comprehensive visit includes screening for depression, anxiety, and traumatic stressor exposure.
We conducted a retrospective chart review on all SCD patients who were medically evaluated between June and October 2013. The study was conducted in accordance with the UConn Health Institutional Review Board. Charts were reviewed for demographic (gender, age, race, and insurance type) and clinical variables (i.e., chronic pain, opioid utilization).
Fifty consecutive adult patients with SCD were evaluated in the adult SCD center over a 5-month study period. Table 1 summarizes demographic and clinical features of the sample.
Demographic and Clinical Comparison of Violence-Exposed vs. Violence-Nonexposed SCD Patients.
Note. SCD = sickle cell disease; PHQ-9 = Patient Health Questionnaire, Nine-Item Version; Zung = Zung Anxiety Scale.
Measures
During the medical evaluations, patients were routinely screened for trauma using the Traumatic Events Screening Inventory (TESI), a standardized interview used to assess trauma exposure history throughout a lifetime (Ford, 2011; Ford, Nader, & Fletcher, 2013; Ford & Smith, 2008). The TESI consists of 18 behaviorally specific, yes/no questions regarding a range of potentially traumatic experiences including physical and sexual assaults, threatened violence, physical and sexual abuse, witnessing family or community violence, serious accidents, losses due to death or separations, and severe illness and related medical care. For example, “Have you ever been in a close relationship with someone who made you fear for your life or feel helpless or trapped?” Items assessing interpersonal forms of violence (i.e., childhood physical, sexual, or emotional abuse; sexual assault; physical assault; and witnessing family or community violence) were used to create two quasi-experimental groups of individuals with and without a history of exposure to interpersonal violence.
Self-reported depressive symptoms were measured using the nine-item Patient Health Questionnaire (PHQ-9) from the Primary Care Evaluation of Mental Disorders (Kroenke & Spitzer, 2002). The PHQ-9 is well validated with demonstrated predictive utility for identifying patients meeting diagnostic criteria for major depression on gold-standard, semistructured diagnostic interviews (Löwe et al., 2004), and other health impairments (Martin, Rief, Klaiberg, & Braehler, 2006). Self-reported anxiety symptoms were assessed using the 20-item Zung Anxiety Scale (Zung, 1971), which has demonstrated test–retest reliability and utility in health care settings (Michelson & Mavissakalian, 1983; Trento et al., 2014). Both instruments have excellent psychometric properties with adults, including specifically in health care settings (Spitzer, Kroenke, & Williams, 1999; Trento et al., 2014).
Self-reported chronic pain was assessed with a single question, inquiring about the presence of moderate to severe pain on more than 50% of days in the past 6 months. Patients’ medical records were used to identify daily opiate users as those with prescriptions for long- or short-acting oral, subcutaneous, or transdermal opiates prescribed for use on a daily basis.
Statistical Analysis
All statistics were conducted with IBM SPSS (Version 19) statistical software. Statistical tests to compare patients with past interpersonal violence exposure and patients with no history of interpersonal violence exposure on demographic and clinical variables included independent groups t tests and chi-square goodness-of-fit (χ2) tests. Associations between continuous variables were examined with Pearson Product-Moment correlations. Finally, multiple logistic regression analyses were conducted to examine whether violence exposure was a significant predictor of chronic pain and opiate use, controlling for age and depressive symptoms. Odds ratios are reported. All tests used a significance threshold set at p < .05.
Results
Table 1 presents comparisons of demographic and clinical variables between the 34 patients who reported past interpersonal violence exposure versus the 16 patients who reported no past interpersonal violence exposure. The subgroups were comparable with respect to gender and race, but interpersonal-violence-exposed patients were older than the nonexposed group. It is worth noting that the relationship between chronic pain and daily opiate use was near perfect, with only two patients (8.7%) with chronic pain who did not use opiates on a daily basis and only one patient (3.7%) with daily opiate use who did not have chronic pain.
Most individuals in the sample reported at least one past nonviolent traumatic experience (Table 2). However, interpersonal-violence-exposed SCD patients were not more likely than nonexposed SCD patients to report nonviolent trauma exposure. However, the interpersonal-violence-exposed group was more likely than the nonexposed SCD patients to endorse being in and/or seeing a severe accident or having someone close who died suddenly or unexpectedly.
Trauma History Comparison of Violence-Exposed vs. Violence-Nonexposed SCD Patients.
Note. SCD = sickle cell disease.
Among interpersonal-violence-exposed patients, the mean number of types of interpersonal violence exposure (including childhood physical, sexual, or emotional abuse; sexual assault; physical assault; and witnessing family or community violence) was 2.76 (SD = 1.63), reflective of the range and degree of violence experienced by these patients.
Consistent with Hypothesis 1, SCD patients exposed to interpersonal violence were more likely than nonexposed SCD patients to report chronic pain and daily use of opiate medications (Table 1). Consistent with Hypothesis 2, interpersonal-violence-exposed SCD patients scored higher than nonexposed SCD patients on depression and anxiety symptoms (Table 1).
Contrary to Hypothesis 2, chronic pain was not significantly associated with depression, t(48) = 1.61, p = .12, or anxiety, t(48) = 1.74, p = .09. Similarly, daily opiate use was not associated with depression, t(48) = 0.56, p = .58, or anxiety, t(48) = 1.47, p = .15.
Depression and anxiety symptoms were highly correlated (r = .80, p < .001), and therefore, subsequent analyses did not include these highly collinear variables together. Depressive symptoms were selected for use in the multivariate analyses based on the relative strength of the relationship between violence exposure and these variables: Interpersonal violence exposure was associated with a 125% increase in the mean levels of depression symptoms as opposed to a 25% increase in mean levels of anxiety.
Two logistic regression analyses were conducted to test Hypothesis 3 by examining the relationship between interpersonal violence exposure and (a) chronic pain and (b) daily opiate use, controlling for age and depressive symptoms. In the first analysis, with chronic pain as the dependent variable and controlling for age and depressive symptoms, interpersonal violence exposure increased the odds of having chronic pain nearly fivefold (B = 1.57, SE = 0.80, Wald’s χ2 = 3.84, p = .05, OR = 4.82, 95% CI = [1.0, 23.24]). In the second analysis, with daily opiate use as a dependent variable and controlling for age and depressive symptoms, interpersonal violence exposure increased the odds of daily opiate use by more than five times (B = 1.88, SE = 0.83, Wald’s χ2 = 5.13, p = .023, OR = 6.57, 95% CI = [1.29, 33.46]).
Discussion
Adults in medical treatment for SCD were found to have extensive lifetime histories of potentially traumatic events, and a subgroup of approximately two thirds of this clinical sample specifically disclosed past exposure to traumatic interpersonal violence. Interpersonal violence exposure typically was not a single incident, nor even a single type, but on average consisted of multiple types of past violence including witnessing violence in their community or family, being personally physically assaulted or abused, and witnessing or directly being victimized by family violence. In addition, almost one third of the violence-exposed subgroup of SCD patients had been sexually assaulted or abused. Thus, this suggests that adults with SCD are at high risk of having been exposed not only to interpersonal violence but also to the cumulative adverse impact of several types of violent victimization (Schoedl, Costa, Fossaluza, Mari, & Mello, 2013).
Violence-exposed SCD patients also were more likely than other SCD patients to have witnessed or been in life-threatening accidents and to have had traumatic losses. Such cumulative trauma, or poly-victimization, puts even the most resilient child, adolescent, or adult at risk of severe physical or medical, as well as mental health problems (Aho, Gren-Landell, & Svedin, 2016; Andrews et al., 2015; da Silva & da Costa Maia, 2013; Noll, 2005; Sledjeski, Speisman, & Dierker, 2008; Thompson et al., 2015; Turner, Shattuck, Finkelhor, & Hamby, 2017; Vaughn et al., 2017; Widom, Horan, & Brzustowicz, 2015).
In the present study, although PTSD was not assessed, two mental health problems closely related to PTSD, anxiety and depression, were examined. Over and above the elevated levels of anxiety and depression symptoms known to be associated with SCD itself, our findings demonstrated that SCD patients with a history of interpersonal violence exposure reported significantly higher levels of both anxiety and depressive symptoms than nonviolence-exposed SCD patients. Thus, violence exposure—including quite distal experiences such as abuse or witnessing family violence in childhood, as well as more recent experiences such as physical or sexual assault or witnessing community violence—appears to have an impact on SCD patients’ psychological state and adjustment that warrants further clinical attention and research.
Further evidence of the potential clinical significance of violence exposure for SCD patients was provided by examining two pain-related indicators of physical health problems that are known to be associated with SCD. After controlling for the effects of depression and age, violence-exposed SCD patients were more than five times more likely to report daily prescription opiate use (557% increased risk) and almost four times more likely to report chronic pain (382% increased risk) than SCD patients who had not been exposed to violence. Despite the strong relationship between violence exposure and heightened depressive symptoms, study results indicate that depression symptoms do not account for the violence-exposed SCD patients’ increased risk of perceptions of chronic pain or daily use of prescription opiates. Future research is needed to examine other potential mediators that can suggest how violence exposure contributes to the already substantial burden of chronic pain and opiate use in SCD patients.
Other sequelae of interpersonal violence exposure that have been linked to chronic pain and opiate use warrant investigation in this SCD population, including posttraumatic stress symptoms of physiological hyperarousal, emotional numbing and dysregulation, chronic avoidance and hypervigilance, dissociation, and stress-related breakdowns in bodily function (Afari et al., 2014; Beckham et al., 1997; Berger, Piralic-Spitzl, & Aigner, 2014; Humphreys, Cooper, & Miaskowski, 2010; Moeller-Bertram, Keltner, & Strigo, 2012; Outcalt et al., 2015; Wuest et al., 2009; Wuest et al., 2008). Variables that have been shown to be associated with the severity of SCD symptoms and SCD-related health care such as SCD-related stigma (Bediako et al., 2016) also should be examined both as contributors to anxiety and depressive symptoms in SCD and as potential mediators of the relationship between violence exposure and chronic pain and opiate use in SCD. In light of evidence that African American patients with chronic pain are more likely than other chronic pain patients to present with complex chronic pain syndrome and/or mild pain that nevertheless was disabling despite comparable levels of anxiety and depression (Green, Ndao-Brumblay, Nagrant, Baker, & Rothman, 2004), it is important to determine whether the posttraumatic sequelae of interpersonal violence exposure warrant assessment and treatment for African American adults with chronic pain (including those with SCD). This is particularly vital given the evidence of the adverse impact of both historical trauma (Bryant-Davis et al., 2015; Nugent, Koenen, & Bradley, 2012) and the risk of exposure to current interpersonal and institutional violence related to racism and socioeconomic disparities (Ducci et al., 2009; Goldmann et al., 2011; Nicolaidis et al., 2010) that adversely affect African Americans.
Although depressive symptoms did not statistically account for variance in the relationship between interpersonal violence exposure and chronic pain or opiate use in SCD, studies with other community and health care populations suggest that depressive and anxiety symptoms often are sequelae of violence exposure that are correlated with pain and substance dependence (Asmundson & Katz, 2009; Bonnewyn et al., 2009; Clark, Reiland, Thorne, & Cropsey, 2014; Macy, Renz, & Pelino, 2013; Paras et al., 2009; Wuest et al., 2008). One possibility worth investigating with a larger SCD sample is that depression or anxiety may influence chronic pain and opiate use in SCD by serving as a moderator of the adverse effects of violence exposure. For example, violence-exposed individuals with SCD who develop problems with anxiety or depression may be more likely than other violence-exposed SCD patients to be impaired by chronic pain and to become dependent on opiates. If tested with a prospective design in which the sequencing of violence exposure, depression and anxiety, and chronic pain and opiate use could be established, this could help clinicians identify and treat the psychological precursors to SCD-related impairments on a timely and empirically grounded basis.
Although our findings suggest a number of directions for future study, methodological limitations should be noted as precautions to interpreting results. The small sample precluded the use of multivariate analyses needed to test mediation and moderation effects systematically. The sample included consecutively evaluated outpatients and, as such, was representative of the patient population at a specialized SCD clinical treatment program; however, replication with randomly selected patients at a variety of SCD treatment sites is needed to ensure generalizable results. The chronic pain and opiate use measures relied upon self-report at a single time point and would be more definitively reliable and valid if confirmed by data obtained longitudinally. Interpersonal violence and other potentially traumatic exposures were assessed with a systematic measure that has been tested in research with a variety of adult populations, but the data were assessed retrospectively, which is subject to memory and emotion state-dependent biases. Although depressive and anxiety symptoms were assessed, PTSD symptoms, which are particularly associated with traumatic violence and have been shown to be associated with pain and addictive behaviors, were not assessed and should be evaluated.
Bearing these limitations in mind, the study’s findings can provide clinicians with practical guidance for providing trauma-informed care for patients with SCD. When SCD patients report chronic pain and potentially seek relief through continuing opiate use, brief sensitive screening for past (and current) violence exposure may enable health care providers to consult with and make referrals to psychological practitioners who conduct evidence-based PTSD evaluations and, when indicated, psychotherapy (Desmarais et al., 2014). PTSD treatment has been shown to complement and enhance both pain management (Peres, Goncalves, & Peres, 2009; Plagge, Lu, Lovejoy, Karl, & Dobscha, 2013) and substance-dependence treatment (Fareed et al., 2013; Frisman, Ford, Lin, Mallon, & Chang, 2008). The current findings reinforce national guidelines regarding the importance of a multidisciplinary approach to the management of SCD that includes integration of physical and mental health services. Such integration could add effective nonpharmacologic interventions (e.g., therapeutic strategies for coping with stress) to the medical/pharmacologic treatments currently provided to individuals with SCD.
In summary, study results indicated that a majority of adults with SCD in a clinical sample were living with chronic pain. Although the contribution of daily life stressors to SCD-associated chronic pain has been previously investigated, this study is the first to elucidate the relationship between exposure to interpersonal violence and both chronic pain and daily opiate use in this population. The fact that this relationship was not simply explained by underlying depression or anxiety symptoms suggests that nonpharmacological therapies focused on the integration of mental health services aimed toward coping with the impact of past or current violent exposures are imperative. Our findings of the high rates of reported exposure to interpersonal violence in this SCD sample, including nearly one third of the participants reporting past exposure to sexual abuse, underscore the need for a multidisciplinary approach to both the medical and psychological needs of this clearly vulnerable population.
Footnotes
Authors’ Note
All procedures involving human participants were performed in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study, formal consent is not required.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by a grant from the Connecticut Institute for Clinical and Translational Science (BA).