522135 research-article2014
DVR0010.1177/1479164114522135Diabetes & Vascular Disease ResearchSelvarajah et al.
Original Article
The contributors of emotional distress in painful diabetic neuropathy
Diabetes & Vascular Disease Research 2014, Vol. 11(4) 218–225 © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/1479164114522135 dvr.sagepub.com
Dinesh Selvarajah1, Thomas Cash1, Adhithya Sankar1, Lloyd Thomas1, Jennifer Davies1, Elaine Cachia1, Rajiv Gandhi2, Iain D Wilkinson1, Nicholas Wilkinson3, Celia J Emery2 and Solomon Tesfaye2
Abstract Aims: To examine the contribution of demographic, social, clinical and psychological factors to emotional distress in patients with painful diabetic neuropathy (DN). Methods: In total, 142 patients with confirmed painful DN underwent detailed clinical and self-assessment measures (Neuropathic Pain Scale, Hospital Anxiety and Depression Scale, Pain Acceptance Questionnaire and Pain Catastrophizing Scale). Results: The prevalence of emotional distress was 51.4% in this cohort. Age, sex, marital status, employment history, pain intensity, duration of diabetes and the presence of diabetic and non-diabetic complications were significantly correlated to anxiety and depressive symptom scores. Multiple regression analysis confirmed that the presence of catastrophic thinking was an independent contributor to greater symptoms of anxiety and depression. Being young, single and unemployed significantly contributed to greater anxiety symptoms. Pain-related restriction of quality of life was associated with greater depression symptom scores. Conclusions: This study found a high prevalence of emotional distress in patients with painful DN. It highlights that the differing independent contributors to anxiety and depressive symptoms are based on an individual’s circumstances and experience. We conclude by highlighting the importance of adopting a holistic approach to pain management, incorporating interventions to increase psychological flexibility alongside conventional pharmacological treatments to improve emotional distress in painful DN. Keywords Painful diabetic neuropathy, emotional distress, depression, anxiety
Introduction Painful diabetic neuropathy (DN) affects up to 26% of patients with DN1 and is among the most distressing complications of diabetes.2 Besides the well-known suffering and disability involved,2 it has a significant socioeconomic impact through high levels of health-care utilisation and reduction in work productivity.3 Unfortunately, there is no cure, with treatment approaches directed at maintenance of glycaemic control and pain management.4 Chronic pain is a subjective experience that comprises both sensory and affective dimensions. The sensory component processes information on the intensity and location of pain. The affective component has cognitive and emotional dimensions, referring to the unpleasantness, suffering and attributed meaning. Over time, there is an increased propensity to develop maladaptive behaviours5 with
substantial interference in activities of daily living and enjoyment of life.6 Not surprisingly, therefore, there is an increased risk of emotional distress,7 which in turn results
1Department
of Human Metabolism, The Medical School, University of Sheffield, Sheffield, UK 2Diabetes Research Department, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK 3Improving Access to Psychological Therapies Sheffield (IAPT), Sheffield Health and Social Care NHS Foundation Trust, Sheffield, UK Corresponding author: Dinesh Selvarajah, Department of Human Metabolism, The Medical School, University of Sheffield, Beech Hill Road, Sheffield S10 2JF, UK. Email: [email protected]
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Selvarajah et al. in greater reported pain intensity and disability.8 The presence of emotional distress can also negatively influence an individual’s response to therapeutic interventions to alleviate pain.9 Previous studies, in other chronic pain conditions, have shown a close association between emotional distress and the pain experience in women more than in men and in younger individuals with lower socio-economic status, greater pain intensity, longer duration and greater disability status.10 Several cross-sectional and longitudinal studies have also shown that illness beliefs and pain-coping mechanisms have significant influences on pain and emotional distress.7 To date, diabetes factors reported to be associated with emotional distress include the following: poor glycaemic control, duration of diabetes and the presence of diabetes complications.11 Few reports have considered the relationship of both diabetes and painful DN on emotional distress together. Those that have, however, mainly reported on the descriptors of pain and the impact of painful DN on quality of life (QOL).1,2 Thus, current knowledge of the contributors to emotional distress in painful DN in the context of diabetes and its complications is very limited. Highlighting these factors can result in early identification and treatment which may tackle the major challenge of improving prognosis.
exercise which had prior approval from the Sheffield Teaching Hospitals NHS Foundation Trust Clinical Governance Department. Patients with both type 1 and 2 diabetes and painful DN who met the inclusion criteria were included in the analysis. Eligibility criteria included the following: male or female patients over 18 years of age, a sufficient level of English to complete the questionnaires, symptoms of painful DN for at least 6-month duration and patients on stable pain-relieving medications. Patients were excluded from the analysis if they had a serious or unstable medical or psychological condition, history of substance abuse including excess alcohol consumption (>20 units per week), neurological disorders or neuropathies other than DN and any other pain condition.
Demographic characteristics and psychosocial determinants of health
We employed a biopsychosocial conceptual approach to explore the relationship between diabetes, chronic pain and symptoms of anxiety and depression. This approach has been used in numerous studies and suits the complexity of painful DN.12 This study adopts a model that integrates key contributors to emotional distress identified in previous studies. Our model includes disease (duration of diabetes and comorbidities, physical disability, pain intensity and duration), biological (age and gender), sociooccupational (socio-economic status, educational level, civil status, work status and social support) and cognitive– behavioural factors (general health, coping strategies and pain control).13 Ultimately the rationale of this study is to provide a model that may have clinical value in the management of painful DN. Therefore, the specific aim is to assess the contribution of demographic, clinical and cognitive–behavioural factors to emotional distress in patients with painful DN.
Basic demographic data and medical history information were obtained from structured interviews and supplemented with information from a computerised clinical database. We chose an observational epidemiology definition of psychosocial factors as any social factor that has an influence on an individual’s mind or behaviour.14 In the context of health research, these are divided into macrolevel socio-economic structures (which relate to ownership and control of property, legal and welfare structures, distribution of income and other resources) and meso-level social processes (such as social networks and support, employment). We used the Index of Multiple Deprivation (IMD) as an indicator of macro-level socio-economic factors connected to mental and physical health outcomes.15 This index measures deprivation in comparison to all other areas in the country based on local authority data from 2004. It is derived from separate indices for income, employment, education, skills and training, health, barriers to housing and services, the living environment and crime. An IMD rank is calculated for each patient where the rank of 1 is assigned to the most deprived and a rank of 32,482 to the least deprived geographical area. Mesolevel social processes recorded for each subject included marital status, employment history (employed or retired at pensionable age vs unemployed or early retirement) and educational level.14
Subjects, materials and methods
Assessment of neuropathy
In this cross-sectional study, we consecutively recruited and performed detailed clinical assessments on patients with moderate to severe painful DN attending our tertiary painful DN multidisciplinary outpatient service in Sheffield. This study was designed as a secondary analysis of data gathered as part of a wider service evaluation
DN was confirmed using the Neuropathy Disability Score (NDS).16 This involved assessing the ankle reflexes and three sensory modalities (10 g monofilament, vibration sensation and temperature sensation). Ankle reflexes were scored as present, reduced or absent (2 points, 1 point and 0 points, respectively). Abnormal sensory
Study objectives
220 modality tests were given a score of 1. A cumulative score of ≥3 was considered the minimum diagnosis for DN. This is a quick and simple tool validated for use in epidemiological studies to confirm the presence of DN. We used this in combination with medical and pain history, supplemented with a questionnaire-based assessment of symptoms to confirm the presence of painful DN.17 Neuropathic symptoms relating to small fibre, large fibre and autonomic involvement were assessed using subscales of the Norfolk Quality of Life in Diabetic Neuropathy (QOL-DN) Questionnaire.18
Questionnaire assessments Independent variables 1. Pain assessment: Neuropathic Pain Scale The primary pain measure in this study was the Neuropathic Pain Scale (NPS).19 The NPS is a 10-question, patientrated instrument designed to assess distinct qualities of neuropathic pain including intensity, heat, dullness, sharpness, sensitivity and unpleasantness. Each measure is assessed on an 11-point numeric rating scale ranging from 0 (no pain) to 10 (most pain imaginable). 2. Behavioural and cognitive assessment: pain catastrophizing and acceptance Chronic pain poses significant challenges in the lives of patients with painful DN. At the root of many of these challenges are the maladaptive behavioural strategies employed to deal with chronic pain. For example, attempts to control or reduce pain can dominate at the expense of other potential goals, and this can lead to reduced QOL, depression and more functional disability. The Chronic Pain Acceptance Questionnaire (CPAQ) assesses the ability of patients to acknowledge and adapt to chronic pain. It provides separate subscores for ‘activities engagement’ and ‘pain willingness’.7 A higher activities engagement score suggests that patients are more likely to pursue activities regardless of pain. While patients with a high willingness score have a greater acceptance that avoidance and control are not viable methods of coping with chronic pain.7 Catastrophizing is a negative cognitive set which affects how patients experience real or anticipated pain. It is a robust predictor of pain outcomes including affective disorders and disability. The Pain Catastrophizing Scale (PCS) assesses a patient’s propensity to develop catastrophizing thinking.20 Respondents rate the degree to which they have certain thoughts and feelings when experiencing pain using a Likert scale ranging from 0 (not at all) to 4 (all the time). Three domains of catastrophizing are produced (rumination, magnification and helplessness).
Diabetes & Vascular Disease Research 11(4) 3. QOL The Norfolk QOL-DN, a DN-specific, self-administered questionnaire was used to assess QOL.18 A health profile comprising four subscales (activities of daily living, small fibre, large fibre and autonomic fibre-related disability) and one summary measure (generic health status) is generated. This tool measures patients’ own perception of the impact of diabetes and DN on their physical and psychological functioning. Its ability to relate neuropathic disabilities to different nerve fibre involvement is an important component of this tool. Patients with painful DN are a heterogeneous group often with co-existing C-fibre, large fibre and autonomic dysfunction. Each can contribute separately towards altering the apparent health and functional status of individuals with painful DN. Hence, using this tool allows us to accurately assess and resolve QOL and activities of daily living into its fibre subtypes. This is a novel component of the study. 4. Symptoms of affective distress The impact of painful DN on anxiety (HADS-A) and depressive (HADS-D) symptoms was evaluated using the Hospital Anxiety and Depression Scale (HADS).21 Each subscale comprises seven items, and subjects assess how each item applies to them on a scale ranging from no feelings of anxiety or depression (score 0) to severe feelings of anxiety or depression (score 3). It focuses on cognitive aspects of affective distress with somatic symptoms deliberately not covered so as to increase the likelihood that the HADS measures affective disorder rather than symptoms of pain, other illness or medication side effects. Although it does not diagnose mood disorders, its psychometric properties as a screening tool for separate dimensions of anxiety and depression have been validated in different study populations.22 Scores range from 0 to 21 for each subscale (0–7 normal, 8–10 mild, 11–14 moderate and 15–21 severe).
Statistical analyses Descriptive statistics were used to describe the study sample, means and standard deviations (SDs) for continuous variables and numbers and percentages for categorical variables. Study questionnaires were scored using standard scoring conventions. Missing data for continuous/ordinal and categorical independent variables were replaced by the overall mean or nearest median for that variable, respectively. For conceptual reasons, measures were divided into four independent variable groups, and analyses were conducted according to methods described by Baron and Kenny.23 We calculated correlation coefficients to determine how each category of independent variables – (1)
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Selvarajah et al. biological: age, gender and body mass index (BMI); (2) social: marital status and deprivation score; (3) clinical: HbA1c, diabetes and pain duration, diabetes complications and other medical comorbidities and NPS and (4) behavioural and psychological: Norfolk QOL-DN and PCS and CPAQ scores – correlated with the dependent variables (HADS-D and HADS-A scores). Variables associated with anxiety and depressive symptoms at p < 0.05 or less were entered in a multiple regression model with backward stepwise removal of factors to obtain a parsimonious model. The variable with the highest p value not significant at the 0.05 level was excluded at each step. Normality of residuals was assessed graphically and through the Kolmogorov–Smirnov test.24 The variance inflation factor was computed to ensure that the independent variables were not highly correlated with each other, with scores above 5 suggesting a problem with the regression model.25 All analyses were conducted using Statistical Package for Social Sciences for Windows, version 16.0 (SPSS Inc., Chicago, IL, USA).
Results A total of 142 patients met study eligibility criteria. Of which, 19 patients were excluded because they had left one or more questionnaires unanswered. The remaining 121 were included. Demographic and clinical characteristics of the study sample are described in Table 1. The mean age of subjects was 61.2 years (SD = 11.2 years), 57.1% were male and 95.7% Caucasian. Average duration of diabetes was 17.2 years (9.9 years), mean pain intensity using a numeric rating scale of 0–10 was 6.3 years (2.7 years) and mean duration of painful symptoms was 8.4 years (6.0 years). The majority had type 2 diabetes (76.4%) with mean HbA1c of 8.1% (1.5%). Participants reported a combination of antidepressant (40.0%), anticonvulsant (35.7%) and opiate (19.3%) medication used to manage their painful neuropathy. A large range of scores were found on HADS. Just over half of patients (51.4%) had scores (subscale scores ≥8) suggestive of significant clinical anxiety and depression and both coexisted in 26.4%. The mean HADS-A and HADS-D scores in our sample population were below the cut-off point for clinical anxiety and depression [7.1 (4.9) and 7.1 (4.4), respectively]. There was also a high prevalence of catastrophic thinking, with patients reporting high levels of helplessness and rumination. These contributed most to the total PCS score (44.7% and 36.7%, respectively).
Relationships between outcome measures HADS-D and HADS-A scores were significantly correlated with age (ρ = −0.37 and −0.34, respectively; p < 0.01), number of microvascular complications (ρ = −0.18,
Table 1. Characteristics of the study population. Variables
Mean (SD), median (range) or n (%)
N Biological Age (years) Gender (male) BMI (kg/m2) Ethnicity White British Afro Caribbean Other Social Educational level Left school 14–16 years A-levels Diploma/undergraduate degree Postgraduate Missing Employment history Currently employed or retired at pensionable age Unemployed or retired before pensionable age Missing Marital status (%, single) Social Deprivation Score Clinical Type 1 diabetes Type 2 diabetes Insulin Tablets Diet Other HbA1c (%) Diabetes duration (years) Pain intensity (NPS Score) Duration of pain (years) Diabetes complications (n) Microvascular Macrovascular Co-morbidity (n) Neuropathic pain medication TCA SNRI Anticonvulsants Opiates Psychological and behavioural HADS-A HADS-D Norfolk QOL PCS Rumination PCS Magnification PCS Helplessness CPAQ Activities CPAQ Willingness
142 61.2 (11.2) 80 (57.1%) 32.6 (6.4) 137 (95.7%) 4 (2.9%) 1 (0.7%)
109 (77.9%) 4 (2.9%) 24 (16.9%) 2 (1.4%) 3 (0.7%) 38 (27.1%) 99 (70.7%) 5 (2.1%) 17 (12.1%) 27.3 (17.5) 33 (23.6%) 64 (45.7%) 37 (26.4%) 1 (0.7%) 7 (3.6%) 8.1 (1.5) 17.2 (9.9) 31.8 (15.2) 8.4 (6.0) 1 (0–3) 1 (0–4) 1 (0–4) 40 (28.6%) 16 (11.4%) 50 (35.7%) 27 (19.3%) 7.1 (4.9) 7.1 (4.4) 33.6 (18.8) 6.8 (5.1) 3.5 (3.2) 8.4 (6.7) 39.7 (13.4) 27.1 (13.4)
Data are represented as mean (SD), median (range) or n (%). BMI: body mass index; TCA: tricyclic antidepressants; SNRI: serotonin noradrenergic receptor inhibitors; HADS: Hospital Anxiety and Depression Scale (-A: Anxiety, -D: Depression); NPS: Neuropathic Pain Scale; QOL: Quality of Life; ADL: Activities of Daily Living; GHS: Generic Health Status; PCS: Pain Catastrophizing Scale; CPAQ: Chronic Pain Acceptance Questionnaire; SD: standard deviation.
222 p = 0.04 and ρ = −0.26, p = 0.003, respectively) and nondiabetic comorbidities (ρ = 0.28, p = 0.001 and 0.21, p = 0.02, respectively). Being a single female, with a shorter duration of diabetes and fewer diabetic microvascular complications was weakly correlated with higher HADS-A but not HADS-D scores. In addition, those who followed a ‘standard’ pathway of employment (employed or retired at pensionable age) had significantly lower anxiety [HADS-A 5.1 (3.1); p = 0.002] and depression [HADS-D 5.3 (3.6); p = 0.004] scores compared to those who were either unemployed or retired early because of ill health [HADS-A 8.0 (5.2); HADS-D 7.7 (4.3)]. Pain intensity as measured by NPS score was more strongly correlated with HADS-A (ρ = 0.45, p < 0.01) compared to HADS-D (ρ = 0.33, p < 0.01). Greater quality-of-life impairment correlated more strongly with HADS-D (ρ = 0.50, p < 0.01) compared with HADS-A (ρ = 0.38, p < 0.01) scores. Higher scores for catastrophizing and lower acceptance of chronic pain were strongly associated with greater levels of anxiety and depressive symptoms. We subsequently performed multiple regression analyses to examine the functional relationships between emotional distress and the independent variables, to explain the variation in our study population. Variables that were included in the depression model were age, employment history, number of diabetic microvascular complications and non-diabetic comorbidities, NPS score, Norfolk QOL score and subscale scores for PCS and CPAQ. These variables together with sex, marital status and diabetes duration were included in the anxiety model. The final regression model revealed that 52% of the variance in HADS-A score could be accounted for by age (β = −0.15, p = 0.05), marital status (β = 0.15, p = 0.02), employment history (β = 0.14, p = 0.05), diabetic microvascular complications (β = −0.15, p = 0.03), PCS helplessness (β = 0.30, p = 0.006) and to a lesser extent PCS magnification (β = 0.19, p = 0.05). Of the variance in HADS-D, 49% was explained mainly by PCS helplessness (β = 0.41, p < 0.001), with a lesser contribution from Norfolk QOL-DN score (β = 0.27, p = 0.003), CPAQ activities engagement (β = −0.27, p = 0.001) and pain intensity (β = −0.15, p = 0.08; Table 2). Because all variation inflation factors were below 2.8, the predictors in the model were not collinear.
Discussion Chronic pain is a complex experience comprising the sensation of pain itself as well as psychological reactions and social consequences. Despite this, current practice is centred solely on pain intensity and does not address the multiple dimensions of the pain experience. We have evaluated the determinants of emotional distress in painful DN by using an integrated biopsychosocial framework. Unlike previous studies, the severity of neuropathy and the presence of other clinical comorbidities were carefully assessed
Diabetes & Vascular Disease Research 11(4) using structured interviews, validated questionnaires and detailed clinical assessment.
Comparisons with other studies There is a large body of literature confirming that anxiety and depression are commonplace among patients with chronic pain. In our cohort, we found a very high prevalence of affective distress (51.4%) and that both symptoms of anxiety and depression commonly coexist. This is similar to prevalence estimates of 40%–50% for depression26 and 25%–29% for anxiety27 reported in other neuropathic pain studies. It is significantly higher than the reported prevalence of mood disorders and affective distress in patients with diabetes.28 A number of studies in a variety of settings (community-based and treatment-seeking), employing different methods for assessing mood disorders in diverse chronic pain syndromes, have documented a strong relationship between chronic pain and depression.29,30 Key factors associated with depression include female gender, younger age at onset, greater levels of pain and disability, pre-existing mood disorders, helplessness and fewer social contacts. Our findings corroborate these reports and also provide new insights by examining both anxiety and depressive symptoms together in the same sample population. For example, we found that being single, unemployed or retired early, with shorter duration of diabetes and fewer diabetic microvascular complications was associated with greater anxiety symptom scores but not depressive symptom scores. Furthermore, greater self-reported pain intensity was more strongly associated with anxiety symptoms compared to depressive symptom scores. Conversely, greater quality-of-life impairment was associated with higher depressive symptom scores. These findings are consistent with studies reporting an inability to fulfil social and family responsibilities as a mediator of the relationship between illness severity and depression.31 The presence of fewer microvascular complications as an independent contributor of greater anxiety symptoms would initially appear to be counterintuitive. However, this could be explained by the natural history of DN which begins with early small fibre involvement, resulting in neuropathic symptoms, often before the development of overt retinopathy or nephropathy. This highlights the vulnerability of younger individuals who develop early small fibre involvement to emotional distress. The reciprocal relationship between affective state and cognitive–interpretive processes resulting in respondent conditioning is well described in the chronic pain literature.32 This theory posits that the experience of pain initiates a set of extremely negative thoughts and arouses fears. This can lead to maladaptive avoidance behaviour which limits activity and contributes to disability and the persistence of pain. As in other models of chronic pain,33 we also
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Selvarajah et al. Table 2. Multiple linear regression analysis of affective distress. HADS-A Social Age Marital status Employment history Clinical Pain intensity Diabetes microvascular complications Norfolk QOL-DN Total QOL score Pain Catastrophizing Scale Helplessness Magnification Chronic Pain Acceptance Questionnaire Activities engagement R2 F
HADS-D
β
t
VIF
−0.15* 0.15* 0.14*
−1.97 2.28 1.97
1.38 1.04 1.13
−0.15*
−2.22
1.07
β
VIF
t
−0.15
−1.78
1.65
0.27*
3.05
1.76
0.30** 0.19
2.81 1.94
2.77 2.28
0.41**
4.65
1.75
−0.15 0.52 17.6***
−1.90
1.47
−0.27* 0.49 27.8***
−3.28
1.50
HADS: Hospital Anxiety and Depression Scale (-A: Anxiety, -D: Depression); Norfolk QOL-DN: Norfolk Quality of Life in Diabetic Neuropathy; β: standardised beta coefficient; VIF: variation inflation factor. * p < 0.05, **p < 0.01, ***p < 0.001.
report that pain-related anxiety (helplessness and magnification) and concerns about harm avoidance (less activities engagement) play an important role in affective distress in painful DN. These may serve as additional vulnerability factors for affective distress, which in the presence of chronic pain may exert a significant impact on functional capacity and pain tolerance. It is noteworthy that being single and unemployed, and thus at risk of isolation, was an independent contributor of greater anxiety symptom scores. This may be due to a predominance of social phobia and agoraphobia reported by previous studies.34 It fits the profile of our cohort of patients who, due to the constant presence of pain, begin to adopt avoidance behaviours (lower CPAQ activities engagement and Norfolk QOL-DN scores), either because of the fear of pain or because of their difficulty in being understood in their social or workplace environment.
Implications for practice Taken together, our findings suggest that vulnerability to affective distress may occur because coping strategies for pain may be less effective in those with less skill in understanding and managing pain and those with weaker social networks. Attention to pain-management skills by focusing on reducing helplessness and increasing acceptance of pain, in combination with group support, may be appropriate for patients with moderate to severe painful DN to reduce the risk of emotional distress.
According to the literature, treating pain aggressively is a possible means of alleviating mood disorders in patients with painful DN.35 This is contrary to our findings which suggest that this simple approach is complicated by other factors independently contributing to emotional distress in painful DN. In this population of patients, focusing on pharmacological treatments that are often ineffective can prove harmful, especially when it dominates all other potential goals. This can increase other discouraging, painful or unwanted psychological experiences such as thoughts, memories and feelings, thereby further reducing QOL. Several interesting findings emerge from this study. Helplessness was strongly associated with the pain experience in DN. There were also strong correlations between anxiety and depressive symptoms with pain willingness and activities engagement scores. This suggests a particular cognitive set in painful DN patients with emotional distress who have an outlook that entrains a helpless orientation, which in turn results in the use of passive or avoidant coping strategies (lower pain willingness scores) and a reluctance to engage in activities (lower CPAQ activities engagement and Norfolk QOL-DN scores). The causality of these relationships needs to be explored further. Effective psychological interventions that specifically target catastrophic thinking and acceptance are readily available.36 Our findings suggest that employing these in a multidisciplinary approach to reduce catastrophic thinking and increase acceptance might lead to meaningful reductions in the level of emotional distress associated with painful DN.
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Strengths and weaknesses of the study A number of limitations of this study need to be considered. The cross-sectional design and lack of a control group limits interpretation of causality in the relationship between our biopsychosocial model and affective symptoms in painful DN. Further prospective studies including a control group of patients with diabetes and no DN are required to determine this. Our study has identified independent contributors for emotional distress that may serve as possible mediators in future studies. Our sample size is relatively small and comprised mostly patients who suffer moderate to severe pain. Our findings may not be generalisable to the entire population of patients with painful DN. Nonetheless, our subjects were well-characterised, and we believe that this study provides an important insight into this particular cohort of patients who pose the greatest challenge to manage. In particular, it highlights possible contributors for the development of emotional distress in painful DN which might have implications for the development of targeted interventions aimed at facilitating adjustment to or promoting greater symptomatic relief. Future studies that focus on the primary care setting are needed to examine the full spectrum of disease severity. We assessed symptoms of anxiety and depression which are common clinical problems rather than major mood disorders, which are less common. Finally, our proposed model only describes 49% and 52% of the variance in HADS-D and HADS-A scores, respectively. Although this accounts for considerably more than models proposed in other studies, it can still be improved upon and highlights the complexity of the relationships involved. Further studies that include novel independent variables (e.g. pain/ mood imaging biomarkers) are required to build on this present literature.
Conclusion This study, in spite of its limitations, has important practical implications for the care of patients with chronic painful DN. The majority of these patients are cared for by primary care physicians and endocrinologists and are not having their needs adequately addressed.3,37 First, this study emphasises the very high prevalence of emotional distress and identifies possible independent contributors. Knowledge of this may help achieve an end result of less disability and improved outcomes for patients experiencing chronic pain. Second, it highlights how anxiety and depression can have different independent contributors, depending on an individual’s circumstances and experience. These biopsychosocial factors could be considered ‘red flags’; as partial indicators of more complex and dynamic distress, which requires tailored management. Future studies should examine the causality of these complex relationships and investigate whether the inclusion of
Diabetes & Vascular Disease Research 11(4) multimodal interventions, which aim to alleviate emotional distress and attenuate the effects of contributors, can yield more positive outcomes for patients being treated for painful DN. Finally, this study highlights the importance of adopting a holistic approach to pain-management incorporating interventions to increase psychological flexibility alongside conventional pharmacological treatments. Declaration of conflicting interests The authors declare that there is no conflict of interest.
Funding This research was supported by a Diabetes UK and Juvenile Diabetes Research Foundation grant.
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225 25. Bair MJ, Robinson RL, Katon W, et al. Depression and pain comorbidity: a literature review. Arch Intern Med 2003; 163: 2433–2445. 26. Gureje O, Von Korff M, Simon GE, et al. Persistent pain and well-being: a World Health Organization Study in Primary Care. JAMA 1998; 280: 147–151. 27. Turk DC, Audette J, Levy RM, et al. Assessment and treatment of psychosocial comorbidities in patients with neuropathic pain. Mayo Clin Proc 2010; 85: S42–S50. 28. Collins MM, Corcoran P and Perry IJ. Anxiety and depression symptoms in patients with diabetes. Diabet Med 2009; 26: 153–161. 29. Rosemann T, Backenstrass M, Joest K, et al. Predictors of depression in a sample of 1,021 primary care patients with osteoarthritis. Arthritis Rheum 2007; 57: 415–422. 30. Tsai PF. Predictors of distress and depression in elders with arthritic pain. J Adv Nurs 2005; 51: 158–165. 31. Williamson GM. The central role of restricted normal activities in adjustment to illness and disability: a model of depressed affect. Rehabil Psychol 1998; 43: 327–347. 32. Vlaeyen JW, Kole-Snijders AM, Boeren RG, et al. Fear of movement/(re)injury in chronic low back pain and its relation to behavioral performance. Pain 1995; 62: 363–372. 33. Vlaeyen JW, Seelen HA, Peters M, et al. Fear of movement/ (re)injury and muscular reactivity in chronic low back pain patients: an experimental investigation. Pain 1999; 82: 297– 304. 34. Means-Christensen AJ, Roy-Byrne PP, Sherbourne CD, et al. Relationships among pain, anxiety, and depression in primary care. Depress Anxiety 2008; 25: 593–600. 35. Fishbain DA, Detke MJ, Wernicke J, et al. The relationship between antidepressant and analgesic responses: findings from six placebo-controlled trials assessing the efficacy of duloxetine in patients with major depressive disorder. Curr Med Res Opin 2008; 24: 3105–3115. 36. Thorn BE, Boothy J and Sullivan MJL. Targeted treatment of catastrophizing in the management of chronic pain. Cogn Behav Pract 2002; 9: 127–138. 37. Daousi C, MacFarlane IA, Woodward A, et al. Chronic painful peripheral neuropathy in an urban community: a controlled comparison of people with and without diabetes. Diabet Med 2004; 21: 976–982.
DVR0010.1177/1479164114522135Diabetes & Vascular Disease ResearchSelvarajah et al.
Original Article
The contributors of emotional distress in painful diabetic neuropathy
Diabetes & Vascular Disease Research 2014, Vol. 11(4) 218–225 © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/1479164114522135 dvr.sagepub.com
Dinesh Selvarajah1, Thomas Cash1, Adhithya Sankar1, Lloyd Thomas1, Jennifer Davies1, Elaine Cachia1, Rajiv Gandhi2, Iain D Wilkinson1, Nicholas Wilkinson3, Celia J Emery2 and Solomon Tesfaye2
Abstract Aims: To examine the contribution of demographic, social, clinical and psychological factors to emotional distress in patients with painful diabetic neuropathy (DN). Methods: In total, 142 patients with confirmed painful DN underwent detailed clinical and self-assessment measures (Neuropathic Pain Scale, Hospital Anxiety and Depression Scale, Pain Acceptance Questionnaire and Pain Catastrophizing Scale). Results: The prevalence of emotional distress was 51.4% in this cohort. Age, sex, marital status, employment history, pain intensity, duration of diabetes and the presence of diabetic and non-diabetic complications were significantly correlated to anxiety and depressive symptom scores. Multiple regression analysis confirmed that the presence of catastrophic thinking was an independent contributor to greater symptoms of anxiety and depression. Being young, single and unemployed significantly contributed to greater anxiety symptoms. Pain-related restriction of quality of life was associated with greater depression symptom scores. Conclusions: This study found a high prevalence of emotional distress in patients with painful DN. It highlights that the differing independent contributors to anxiety and depressive symptoms are based on an individual’s circumstances and experience. We conclude by highlighting the importance of adopting a holistic approach to pain management, incorporating interventions to increase psychological flexibility alongside conventional pharmacological treatments to improve emotional distress in painful DN. Keywords Painful diabetic neuropathy, emotional distress, depression, anxiety
Introduction Painful diabetic neuropathy (DN) affects up to 26% of patients with DN1 and is among the most distressing complications of diabetes.2 Besides the well-known suffering and disability involved,2 it has a significant socioeconomic impact through high levels of health-care utilisation and reduction in work productivity.3 Unfortunately, there is no cure, with treatment approaches directed at maintenance of glycaemic control and pain management.4 Chronic pain is a subjective experience that comprises both sensory and affective dimensions. The sensory component processes information on the intensity and location of pain. The affective component has cognitive and emotional dimensions, referring to the unpleasantness, suffering and attributed meaning. Over time, there is an increased propensity to develop maladaptive behaviours5 with
substantial interference in activities of daily living and enjoyment of life.6 Not surprisingly, therefore, there is an increased risk of emotional distress,7 which in turn results
1Department
of Human Metabolism, The Medical School, University of Sheffield, Sheffield, UK 2Diabetes Research Department, Royal Hallamshire Hospital, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, UK 3Improving Access to Psychological Therapies Sheffield (IAPT), Sheffield Health and Social Care NHS Foundation Trust, Sheffield, UK Corresponding author: Dinesh Selvarajah, Department of Human Metabolism, The Medical School, University of Sheffield, Beech Hill Road, Sheffield S10 2JF, UK. Email: [email protected]
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Selvarajah et al. in greater reported pain intensity and disability.8 The presence of emotional distress can also negatively influence an individual’s response to therapeutic interventions to alleviate pain.9 Previous studies, in other chronic pain conditions, have shown a close association between emotional distress and the pain experience in women more than in men and in younger individuals with lower socio-economic status, greater pain intensity, longer duration and greater disability status.10 Several cross-sectional and longitudinal studies have also shown that illness beliefs and pain-coping mechanisms have significant influences on pain and emotional distress.7 To date, diabetes factors reported to be associated with emotional distress include the following: poor glycaemic control, duration of diabetes and the presence of diabetes complications.11 Few reports have considered the relationship of both diabetes and painful DN on emotional distress together. Those that have, however, mainly reported on the descriptors of pain and the impact of painful DN on quality of life (QOL).1,2 Thus, current knowledge of the contributors to emotional distress in painful DN in the context of diabetes and its complications is very limited. Highlighting these factors can result in early identification and treatment which may tackle the major challenge of improving prognosis.
exercise which had prior approval from the Sheffield Teaching Hospitals NHS Foundation Trust Clinical Governance Department. Patients with both type 1 and 2 diabetes and painful DN who met the inclusion criteria were included in the analysis. Eligibility criteria included the following: male or female patients over 18 years of age, a sufficient level of English to complete the questionnaires, symptoms of painful DN for at least 6-month duration and patients on stable pain-relieving medications. Patients were excluded from the analysis if they had a serious or unstable medical or psychological condition, history of substance abuse including excess alcohol consumption (>20 units per week), neurological disorders or neuropathies other than DN and any other pain condition.
Demographic characteristics and psychosocial determinants of health
We employed a biopsychosocial conceptual approach to explore the relationship between diabetes, chronic pain and symptoms of anxiety and depression. This approach has been used in numerous studies and suits the complexity of painful DN.12 This study adopts a model that integrates key contributors to emotional distress identified in previous studies. Our model includes disease (duration of diabetes and comorbidities, physical disability, pain intensity and duration), biological (age and gender), sociooccupational (socio-economic status, educational level, civil status, work status and social support) and cognitive– behavioural factors (general health, coping strategies and pain control).13 Ultimately the rationale of this study is to provide a model that may have clinical value in the management of painful DN. Therefore, the specific aim is to assess the contribution of demographic, clinical and cognitive–behavioural factors to emotional distress in patients with painful DN.
Basic demographic data and medical history information were obtained from structured interviews and supplemented with information from a computerised clinical database. We chose an observational epidemiology definition of psychosocial factors as any social factor that has an influence on an individual’s mind or behaviour.14 In the context of health research, these are divided into macrolevel socio-economic structures (which relate to ownership and control of property, legal and welfare structures, distribution of income and other resources) and meso-level social processes (such as social networks and support, employment). We used the Index of Multiple Deprivation (IMD) as an indicator of macro-level socio-economic factors connected to mental and physical health outcomes.15 This index measures deprivation in comparison to all other areas in the country based on local authority data from 2004. It is derived from separate indices for income, employment, education, skills and training, health, barriers to housing and services, the living environment and crime. An IMD rank is calculated for each patient where the rank of 1 is assigned to the most deprived and a rank of 32,482 to the least deprived geographical area. Mesolevel social processes recorded for each subject included marital status, employment history (employed or retired at pensionable age vs unemployed or early retirement) and educational level.14
Subjects, materials and methods
Assessment of neuropathy
In this cross-sectional study, we consecutively recruited and performed detailed clinical assessments on patients with moderate to severe painful DN attending our tertiary painful DN multidisciplinary outpatient service in Sheffield. This study was designed as a secondary analysis of data gathered as part of a wider service evaluation
DN was confirmed using the Neuropathy Disability Score (NDS).16 This involved assessing the ankle reflexes and three sensory modalities (10 g monofilament, vibration sensation and temperature sensation). Ankle reflexes were scored as present, reduced or absent (2 points, 1 point and 0 points, respectively). Abnormal sensory
Study objectives
220 modality tests were given a score of 1. A cumulative score of ≥3 was considered the minimum diagnosis for DN. This is a quick and simple tool validated for use in epidemiological studies to confirm the presence of DN. We used this in combination with medical and pain history, supplemented with a questionnaire-based assessment of symptoms to confirm the presence of painful DN.17 Neuropathic symptoms relating to small fibre, large fibre and autonomic involvement were assessed using subscales of the Norfolk Quality of Life in Diabetic Neuropathy (QOL-DN) Questionnaire.18
Questionnaire assessments Independent variables 1. Pain assessment: Neuropathic Pain Scale The primary pain measure in this study was the Neuropathic Pain Scale (NPS).19 The NPS is a 10-question, patientrated instrument designed to assess distinct qualities of neuropathic pain including intensity, heat, dullness, sharpness, sensitivity and unpleasantness. Each measure is assessed on an 11-point numeric rating scale ranging from 0 (no pain) to 10 (most pain imaginable). 2. Behavioural and cognitive assessment: pain catastrophizing and acceptance Chronic pain poses significant challenges in the lives of patients with painful DN. At the root of many of these challenges are the maladaptive behavioural strategies employed to deal with chronic pain. For example, attempts to control or reduce pain can dominate at the expense of other potential goals, and this can lead to reduced QOL, depression and more functional disability. The Chronic Pain Acceptance Questionnaire (CPAQ) assesses the ability of patients to acknowledge and adapt to chronic pain. It provides separate subscores for ‘activities engagement’ and ‘pain willingness’.7 A higher activities engagement score suggests that patients are more likely to pursue activities regardless of pain. While patients with a high willingness score have a greater acceptance that avoidance and control are not viable methods of coping with chronic pain.7 Catastrophizing is a negative cognitive set which affects how patients experience real or anticipated pain. It is a robust predictor of pain outcomes including affective disorders and disability. The Pain Catastrophizing Scale (PCS) assesses a patient’s propensity to develop catastrophizing thinking.20 Respondents rate the degree to which they have certain thoughts and feelings when experiencing pain using a Likert scale ranging from 0 (not at all) to 4 (all the time). Three domains of catastrophizing are produced (rumination, magnification and helplessness).
Diabetes & Vascular Disease Research 11(4) 3. QOL The Norfolk QOL-DN, a DN-specific, self-administered questionnaire was used to assess QOL.18 A health profile comprising four subscales (activities of daily living, small fibre, large fibre and autonomic fibre-related disability) and one summary measure (generic health status) is generated. This tool measures patients’ own perception of the impact of diabetes and DN on their physical and psychological functioning. Its ability to relate neuropathic disabilities to different nerve fibre involvement is an important component of this tool. Patients with painful DN are a heterogeneous group often with co-existing C-fibre, large fibre and autonomic dysfunction. Each can contribute separately towards altering the apparent health and functional status of individuals with painful DN. Hence, using this tool allows us to accurately assess and resolve QOL and activities of daily living into its fibre subtypes. This is a novel component of the study. 4. Symptoms of affective distress The impact of painful DN on anxiety (HADS-A) and depressive (HADS-D) symptoms was evaluated using the Hospital Anxiety and Depression Scale (HADS).21 Each subscale comprises seven items, and subjects assess how each item applies to them on a scale ranging from no feelings of anxiety or depression (score 0) to severe feelings of anxiety or depression (score 3). It focuses on cognitive aspects of affective distress with somatic symptoms deliberately not covered so as to increase the likelihood that the HADS measures affective disorder rather than symptoms of pain, other illness or medication side effects. Although it does not diagnose mood disorders, its psychometric properties as a screening tool for separate dimensions of anxiety and depression have been validated in different study populations.22 Scores range from 0 to 21 for each subscale (0–7 normal, 8–10 mild, 11–14 moderate and 15–21 severe).
Statistical analyses Descriptive statistics were used to describe the study sample, means and standard deviations (SDs) for continuous variables and numbers and percentages for categorical variables. Study questionnaires were scored using standard scoring conventions. Missing data for continuous/ordinal and categorical independent variables were replaced by the overall mean or nearest median for that variable, respectively. For conceptual reasons, measures were divided into four independent variable groups, and analyses were conducted according to methods described by Baron and Kenny.23 We calculated correlation coefficients to determine how each category of independent variables – (1)
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Selvarajah et al. biological: age, gender and body mass index (BMI); (2) social: marital status and deprivation score; (3) clinical: HbA1c, diabetes and pain duration, diabetes complications and other medical comorbidities and NPS and (4) behavioural and psychological: Norfolk QOL-DN and PCS and CPAQ scores – correlated with the dependent variables (HADS-D and HADS-A scores). Variables associated with anxiety and depressive symptoms at p < 0.05 or less were entered in a multiple regression model with backward stepwise removal of factors to obtain a parsimonious model. The variable with the highest p value not significant at the 0.05 level was excluded at each step. Normality of residuals was assessed graphically and through the Kolmogorov–Smirnov test.24 The variance inflation factor was computed to ensure that the independent variables were not highly correlated with each other, with scores above 5 suggesting a problem with the regression model.25 All analyses were conducted using Statistical Package for Social Sciences for Windows, version 16.0 (SPSS Inc., Chicago, IL, USA).
Results A total of 142 patients met study eligibility criteria. Of which, 19 patients were excluded because they had left one or more questionnaires unanswered. The remaining 121 were included. Demographic and clinical characteristics of the study sample are described in Table 1. The mean age of subjects was 61.2 years (SD = 11.2 years), 57.1% were male and 95.7% Caucasian. Average duration of diabetes was 17.2 years (9.9 years), mean pain intensity using a numeric rating scale of 0–10 was 6.3 years (2.7 years) and mean duration of painful symptoms was 8.4 years (6.0 years). The majority had type 2 diabetes (76.4%) with mean HbA1c of 8.1% (1.5%). Participants reported a combination of antidepressant (40.0%), anticonvulsant (35.7%) and opiate (19.3%) medication used to manage their painful neuropathy. A large range of scores were found on HADS. Just over half of patients (51.4%) had scores (subscale scores ≥8) suggestive of significant clinical anxiety and depression and both coexisted in 26.4%. The mean HADS-A and HADS-D scores in our sample population were below the cut-off point for clinical anxiety and depression [7.1 (4.9) and 7.1 (4.4), respectively]. There was also a high prevalence of catastrophic thinking, with patients reporting high levels of helplessness and rumination. These contributed most to the total PCS score (44.7% and 36.7%, respectively).
Relationships between outcome measures HADS-D and HADS-A scores were significantly correlated with age (ρ = −0.37 and −0.34, respectively; p < 0.01), number of microvascular complications (ρ = −0.18,
Table 1. Characteristics of the study population. Variables
Mean (SD), median (range) or n (%)
N Biological Age (years) Gender (male) BMI (kg/m2) Ethnicity White British Afro Caribbean Other Social Educational level Left school 14–16 years A-levels Diploma/undergraduate degree Postgraduate Missing Employment history Currently employed or retired at pensionable age Unemployed or retired before pensionable age Missing Marital status (%, single) Social Deprivation Score Clinical Type 1 diabetes Type 2 diabetes Insulin Tablets Diet Other HbA1c (%) Diabetes duration (years) Pain intensity (NPS Score) Duration of pain (years) Diabetes complications (n) Microvascular Macrovascular Co-morbidity (n) Neuropathic pain medication TCA SNRI Anticonvulsants Opiates Psychological and behavioural HADS-A HADS-D Norfolk QOL PCS Rumination PCS Magnification PCS Helplessness CPAQ Activities CPAQ Willingness
142 61.2 (11.2) 80 (57.1%) 32.6 (6.4) 137 (95.7%) 4 (2.9%) 1 (0.7%)
109 (77.9%) 4 (2.9%) 24 (16.9%) 2 (1.4%) 3 (0.7%) 38 (27.1%) 99 (70.7%) 5 (2.1%) 17 (12.1%) 27.3 (17.5) 33 (23.6%) 64 (45.7%) 37 (26.4%) 1 (0.7%) 7 (3.6%) 8.1 (1.5) 17.2 (9.9) 31.8 (15.2) 8.4 (6.0) 1 (0–3) 1 (0–4) 1 (0–4) 40 (28.6%) 16 (11.4%) 50 (35.7%) 27 (19.3%) 7.1 (4.9) 7.1 (4.4) 33.6 (18.8) 6.8 (5.1) 3.5 (3.2) 8.4 (6.7) 39.7 (13.4) 27.1 (13.4)
Data are represented as mean (SD), median (range) or n (%). BMI: body mass index; TCA: tricyclic antidepressants; SNRI: serotonin noradrenergic receptor inhibitors; HADS: Hospital Anxiety and Depression Scale (-A: Anxiety, -D: Depression); NPS: Neuropathic Pain Scale; QOL: Quality of Life; ADL: Activities of Daily Living; GHS: Generic Health Status; PCS: Pain Catastrophizing Scale; CPAQ: Chronic Pain Acceptance Questionnaire; SD: standard deviation.
222 p = 0.04 and ρ = −0.26, p = 0.003, respectively) and nondiabetic comorbidities (ρ = 0.28, p = 0.001 and 0.21, p = 0.02, respectively). Being a single female, with a shorter duration of diabetes and fewer diabetic microvascular complications was weakly correlated with higher HADS-A but not HADS-D scores. In addition, those who followed a ‘standard’ pathway of employment (employed or retired at pensionable age) had significantly lower anxiety [HADS-A 5.1 (3.1); p = 0.002] and depression [HADS-D 5.3 (3.6); p = 0.004] scores compared to those who were either unemployed or retired early because of ill health [HADS-A 8.0 (5.2); HADS-D 7.7 (4.3)]. Pain intensity as measured by NPS score was more strongly correlated with HADS-A (ρ = 0.45, p < 0.01) compared to HADS-D (ρ = 0.33, p < 0.01). Greater quality-of-life impairment correlated more strongly with HADS-D (ρ = 0.50, p < 0.01) compared with HADS-A (ρ = 0.38, p < 0.01) scores. Higher scores for catastrophizing and lower acceptance of chronic pain were strongly associated with greater levels of anxiety and depressive symptoms. We subsequently performed multiple regression analyses to examine the functional relationships between emotional distress and the independent variables, to explain the variation in our study population. Variables that were included in the depression model were age, employment history, number of diabetic microvascular complications and non-diabetic comorbidities, NPS score, Norfolk QOL score and subscale scores for PCS and CPAQ. These variables together with sex, marital status and diabetes duration were included in the anxiety model. The final regression model revealed that 52% of the variance in HADS-A score could be accounted for by age (β = −0.15, p = 0.05), marital status (β = 0.15, p = 0.02), employment history (β = 0.14, p = 0.05), diabetic microvascular complications (β = −0.15, p = 0.03), PCS helplessness (β = 0.30, p = 0.006) and to a lesser extent PCS magnification (β = 0.19, p = 0.05). Of the variance in HADS-D, 49% was explained mainly by PCS helplessness (β = 0.41, p < 0.001), with a lesser contribution from Norfolk QOL-DN score (β = 0.27, p = 0.003), CPAQ activities engagement (β = −0.27, p = 0.001) and pain intensity (β = −0.15, p = 0.08; Table 2). Because all variation inflation factors were below 2.8, the predictors in the model were not collinear.
Discussion Chronic pain is a complex experience comprising the sensation of pain itself as well as psychological reactions and social consequences. Despite this, current practice is centred solely on pain intensity and does not address the multiple dimensions of the pain experience. We have evaluated the determinants of emotional distress in painful DN by using an integrated biopsychosocial framework. Unlike previous studies, the severity of neuropathy and the presence of other clinical comorbidities were carefully assessed
Diabetes & Vascular Disease Research 11(4) using structured interviews, validated questionnaires and detailed clinical assessment.
Comparisons with other studies There is a large body of literature confirming that anxiety and depression are commonplace among patients with chronic pain. In our cohort, we found a very high prevalence of affective distress (51.4%) and that both symptoms of anxiety and depression commonly coexist. This is similar to prevalence estimates of 40%–50% for depression26 and 25%–29% for anxiety27 reported in other neuropathic pain studies. It is significantly higher than the reported prevalence of mood disorders and affective distress in patients with diabetes.28 A number of studies in a variety of settings (community-based and treatment-seeking), employing different methods for assessing mood disorders in diverse chronic pain syndromes, have documented a strong relationship between chronic pain and depression.29,30 Key factors associated with depression include female gender, younger age at onset, greater levels of pain and disability, pre-existing mood disorders, helplessness and fewer social contacts. Our findings corroborate these reports and also provide new insights by examining both anxiety and depressive symptoms together in the same sample population. For example, we found that being single, unemployed or retired early, with shorter duration of diabetes and fewer diabetic microvascular complications was associated with greater anxiety symptom scores but not depressive symptom scores. Furthermore, greater self-reported pain intensity was more strongly associated with anxiety symptoms compared to depressive symptom scores. Conversely, greater quality-of-life impairment was associated with higher depressive symptom scores. These findings are consistent with studies reporting an inability to fulfil social and family responsibilities as a mediator of the relationship between illness severity and depression.31 The presence of fewer microvascular complications as an independent contributor of greater anxiety symptoms would initially appear to be counterintuitive. However, this could be explained by the natural history of DN which begins with early small fibre involvement, resulting in neuropathic symptoms, often before the development of overt retinopathy or nephropathy. This highlights the vulnerability of younger individuals who develop early small fibre involvement to emotional distress. The reciprocal relationship between affective state and cognitive–interpretive processes resulting in respondent conditioning is well described in the chronic pain literature.32 This theory posits that the experience of pain initiates a set of extremely negative thoughts and arouses fears. This can lead to maladaptive avoidance behaviour which limits activity and contributes to disability and the persistence of pain. As in other models of chronic pain,33 we also
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Selvarajah et al. Table 2. Multiple linear regression analysis of affective distress. HADS-A Social Age Marital status Employment history Clinical Pain intensity Diabetes microvascular complications Norfolk QOL-DN Total QOL score Pain Catastrophizing Scale Helplessness Magnification Chronic Pain Acceptance Questionnaire Activities engagement R2 F
HADS-D
β
t
VIF
−0.15* 0.15* 0.14*
−1.97 2.28 1.97
1.38 1.04 1.13
−0.15*
−2.22
1.07
β
VIF
t
−0.15
−1.78
1.65
0.27*
3.05
1.76
0.30** 0.19
2.81 1.94
2.77 2.28
0.41**
4.65
1.75
−0.15 0.52 17.6***
−1.90
1.47
−0.27* 0.49 27.8***
−3.28
1.50
HADS: Hospital Anxiety and Depression Scale (-A: Anxiety, -D: Depression); Norfolk QOL-DN: Norfolk Quality of Life in Diabetic Neuropathy; β: standardised beta coefficient; VIF: variation inflation factor. * p < 0.05, **p < 0.01, ***p < 0.001.
report that pain-related anxiety (helplessness and magnification) and concerns about harm avoidance (less activities engagement) play an important role in affective distress in painful DN. These may serve as additional vulnerability factors for affective distress, which in the presence of chronic pain may exert a significant impact on functional capacity and pain tolerance. It is noteworthy that being single and unemployed, and thus at risk of isolation, was an independent contributor of greater anxiety symptom scores. This may be due to a predominance of social phobia and agoraphobia reported by previous studies.34 It fits the profile of our cohort of patients who, due to the constant presence of pain, begin to adopt avoidance behaviours (lower CPAQ activities engagement and Norfolk QOL-DN scores), either because of the fear of pain or because of their difficulty in being understood in their social or workplace environment.
Implications for practice Taken together, our findings suggest that vulnerability to affective distress may occur because coping strategies for pain may be less effective in those with less skill in understanding and managing pain and those with weaker social networks. Attention to pain-management skills by focusing on reducing helplessness and increasing acceptance of pain, in combination with group support, may be appropriate for patients with moderate to severe painful DN to reduce the risk of emotional distress.
According to the literature, treating pain aggressively is a possible means of alleviating mood disorders in patients with painful DN.35 This is contrary to our findings which suggest that this simple approach is complicated by other factors independently contributing to emotional distress in painful DN. In this population of patients, focusing on pharmacological treatments that are often ineffective can prove harmful, especially when it dominates all other potential goals. This can increase other discouraging, painful or unwanted psychological experiences such as thoughts, memories and feelings, thereby further reducing QOL. Several interesting findings emerge from this study. Helplessness was strongly associated with the pain experience in DN. There were also strong correlations between anxiety and depressive symptoms with pain willingness and activities engagement scores. This suggests a particular cognitive set in painful DN patients with emotional distress who have an outlook that entrains a helpless orientation, which in turn results in the use of passive or avoidant coping strategies (lower pain willingness scores) and a reluctance to engage in activities (lower CPAQ activities engagement and Norfolk QOL-DN scores). The causality of these relationships needs to be explored further. Effective psychological interventions that specifically target catastrophic thinking and acceptance are readily available.36 Our findings suggest that employing these in a multidisciplinary approach to reduce catastrophic thinking and increase acceptance might lead to meaningful reductions in the level of emotional distress associated with painful DN.
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Strengths and weaknesses of the study A number of limitations of this study need to be considered. The cross-sectional design and lack of a control group limits interpretation of causality in the relationship between our biopsychosocial model and affective symptoms in painful DN. Further prospective studies including a control group of patients with diabetes and no DN are required to determine this. Our study has identified independent contributors for emotional distress that may serve as possible mediators in future studies. Our sample size is relatively small and comprised mostly patients who suffer moderate to severe pain. Our findings may not be generalisable to the entire population of patients with painful DN. Nonetheless, our subjects were well-characterised, and we believe that this study provides an important insight into this particular cohort of patients who pose the greatest challenge to manage. In particular, it highlights possible contributors for the development of emotional distress in painful DN which might have implications for the development of targeted interventions aimed at facilitating adjustment to or promoting greater symptomatic relief. Future studies that focus on the primary care setting are needed to examine the full spectrum of disease severity. We assessed symptoms of anxiety and depression which are common clinical problems rather than major mood disorders, which are less common. Finally, our proposed model only describes 49% and 52% of the variance in HADS-D and HADS-A scores, respectively. Although this accounts for considerably more than models proposed in other studies, it can still be improved upon and highlights the complexity of the relationships involved. Further studies that include novel independent variables (e.g. pain/ mood imaging biomarkers) are required to build on this present literature.
Conclusion This study, in spite of its limitations, has important practical implications for the care of patients with chronic painful DN. The majority of these patients are cared for by primary care physicians and endocrinologists and are not having their needs adequately addressed.3,37 First, this study emphasises the very high prevalence of emotional distress and identifies possible independent contributors. Knowledge of this may help achieve an end result of less disability and improved outcomes for patients experiencing chronic pain. Second, it highlights how anxiety and depression can have different independent contributors, depending on an individual’s circumstances and experience. These biopsychosocial factors could be considered ‘red flags’; as partial indicators of more complex and dynamic distress, which requires tailored management. Future studies should examine the causality of these complex relationships and investigate whether the inclusion of
Diabetes & Vascular Disease Research 11(4) multimodal interventions, which aim to alleviate emotional distress and attenuate the effects of contributors, can yield more positive outcomes for patients being treated for painful DN. Finally, this study highlights the importance of adopting a holistic approach to pain-management incorporating interventions to increase psychological flexibility alongside conventional pharmacological treatments. Declaration of conflicting interests The authors declare that there is no conflict of interest.
Funding This research was supported by a Diabetes UK and Juvenile Diabetes Research Foundation grant.
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