Pain-related and psychological factors mediate the effect of personality on health-related quality of life. A study in breast cancer survivors with persistent pain.

Introduction: Personality characteristics affect the long-term well-being and health-related quality of life (HrQoL) of breast cancer (BC) survivors. Persistent pain significantly affects psychosocial well-being and HrQoL in this patient group. We studied the effects of temperament and character via pain-related and psychological factors on dimensions of HrQoL in BC survivors. Methods: We studied 273 patients who had been treated for BC and who reported persistent pain at any site of the body in Brief Pain Inventory. The patients were recruited from a longitudinal cohort of patients 4-9 years after surgery for BC. Short-Form-36 inventory was used to assess physical and mental dimensions of HrQoL and Temperament and Character Inventory to assess dimensions of temperament and character. We used parallel mediation modeling for studying effects of temperament and character on physical and mental HrQoL. Results: A significant total effect was found for harm avoidance (HA) temperament (ßtotal = -0.665, p < 0.001) and character dimensions self-directedness (SD) (ßtotal = 0.609, p = 0.001) and cooperativeness (CO) (ßtotal = 0.584, p = 0.028) on physical and mental HrQoL. Additionally, different combinations of pain-related and psychological variables fully mediated the indirect effects of HA, SD, and CO on physical and mental HrQoL. Discussion: HA temperament is a potential emotional vulnerability factor for psychological burden and impaired HrQoL in BC survivors. Character dimensions SD and CO may protect from the negative effect of mood on HrQoL. The results provide new insights about the risk-and target-factors for clinical interventions and effective pain management to improve psychosocial well-being and HrQoL in BC survivors.

Cognitive function is well preserved in a cohort of breast cancer survivors: Roles of cognitive reserve, resilience, and general health.

Many patients return to cognitively demanding work after breast cancer treatments. This makes treatment-related cognitive decline an important research topic. Psychological resilience, cognitive reserve and better perceived general health may work as protective factors against cognitive decline. The aim of this study was to analyse whether these factors are associated with cognitive function among such women. Data from 384 breast cancer survivors who underwent neuropsychological examination at follow-up 4-9 years after surgery were used. The neurocognitive domain variable Learning and Memory was computed from Wechsler Memory Scale-III subtests Learning and Delayed Recall. Another variable, Attention, Processing speed and Executive function, was computed from semantic and verbal fluency tests, Trail Making Test A and B, and Wechsler Adult Intelligence Test-IV subtest Coding. Psychological resilience was measured with Resilience Scale-14, and perceived general health with RAND-36 subitem General Health. RESULTS: showed that levels of cognitive performance and general health were statistically higher than population average. Resilience and general health in separate models were associated with Attention, Processing speed and Executive function (ß = 0.14, p = 0.01; ß = 0.13, p = 0.03, respectively). When added simultaneously in the same model, resilience was significant (ß = 0.13, p = 0.04), but general health was not. These associations were nonsignificant after controlling for confounding factors. Learning and Memory was not associated with resilience or general health. Future research should focus on longitudinal studies identifying patients at a high risk of developing cognitive decline after breast cancer treatments and on preventive and therapeutic approaches.

Temperament and character dimensions differ in chronic post-surgical neuropathic pain and cold pressure pain.

OBJECTIVES: Psychobiological temperament and cognitive-evaluative character link to coping with chronic pain. The aim was to study possible independent role of temperament and character dimensions both in chronic and experimental pain in chronic post-surgical pain patients. This is a substudy of a previously published larger cohort of patients with intercostobrachial nerve injury after breast cancer surgery. METHODS: We recruited 241 women who had been treated for breast cancer 4-9 years before. They had a surgeon-verified intercostobrachial nerve injury with or without chronic post-surgical neuropathic pain (CPSNP). The patients filled in the Temperament and Character Inventory (TCI), Pain Catastrophizing Scale (PCS), Hospital Anxiety and Depression Scale (HADS), and Brief Pain Inventory (BPI), and underwent the cold pressor test (CPT). RESULTS: 201 (83%) patients reported chronic pain and 135 (56%) met the criteria for CPSNP. Patients with CPSNP showed higher levels of Harm Avoidance (HA) temperament than non-CPSNP patients, which was associated with lower cold pain tolerance and greater increase of pain intensity during CPT. HA subscales Fear of Uncertainty and Fatigability contributed to a stronger pain experience. For character dimensions, CPSNP patients reported higher levels of Self-Transcendence (ST) and lower levels of Self-Directedness (SD) and Cooperativeness (CO) than non-CPSNP patients. Cold pain tolerance, intensity, or unpleasantness did not associate with character dimensions. CONCLUSIONS: Psychobiological temperament, but not character, is independently from other psychological factors associated with primary pain processing in an experimental pain setting. Patients with and without CPSNP showed different profiles on both temperament and character dimensions suggesting a combination of heightened emotional vulnerability and lowered personality adaptability in CPSNP patients. Character dimensions associated with clinical but not experimental pain. ETHICAL COMMITTEE NUMBER: The study protocol was approved by the Ethics Committee of the Helsinki and Uusimaa Hospital District (reference number: 149/13/03/00/14). TRIAL REGISTRY NUMBER: The study is registered in ClinicalTrials.gov (NCT02487524).

Sleep Well and Recover Faster with Less Pain-A Narrative Review on Sleep in the Perioperative Period.

Sleep disturbance, pain, and having a surgical procedure of some kind are all very likely to occur during the average lifespan. Postoperative pain continues to be a prevalent problem and growing evidence supports the association between pain and sleep disturbances. The bidirectional nature of sleep and pain is widely acknowledged. A decline in sleep quality adds a risk for the onset of pain and also exacerbates existing pain. The risk factors for developing insomnia and experiencing severe pain after surgery are quite similar. The main aim of this narrative review is to discuss why it is important to be aware of sleep disturbances both before and after surgery, to know how sleep disturbances should be assessed and monitored, and to understand how better sleep can be supported by both pharmacological and non-pharmacological interventions.

Health-related quality of life and pain interference in two patient cohorts with neuropathic pain: breast cancer survivors and HIV patients.

OBJECTIVES: Persistent pain is common in HIV patients and breast cancer (BC) survivors. The aim of this study was to compare two patient groups with neuropathic pain (NP) regarding several psychological variables and Health-related Quality of Life. Although, treatment of pain is always planned individually, the knowledge of the differences and similarities between the patient groups may help us to understand more precisely the targets of the interventions for pain. METHODS: Eighty nine BC and 73 HIV patients with symptoms of neuropathic pain (patients with ≥3/7 in the Douleur Neuropathique four interview part (DN4i)) participated in a cross-sectional study. Patients completed questionnaires about mood (HADS), symptoms of insomnia (ISI), pain catastrophizing (PCS), personality (TIPI), Mental and Physical Health-related Quality of Life (M/PHrQoL, RAND/SF-36), and pain intensity and interference (BPI). Analyses were applied by using t-tests and linear regression to assess associations between the studied factors. RESULTS: HIV patients reported higher anxiety (p<0.001), depressive symptoms (p<0.001), pain catastrophizing (p<0.001) and pain interference (p<0.001), poorer sleep (p<0.001), and lower HrQoL in all dimensions compared with BC survivors. There were significant differences in personality traits extraversion, emotional stability, and agreeableness between the two patient groups. In HIV patients, pain interference (ß=-0.344, p<0.001) and mood (ß=-0.580, p<0.001) and in the BC group, mood (ß=-0.591, p<0.001), extraversion (ß=0.229, p=0.005) and sleep (ß=-0.154, p=0.042) associated with MHrQoL. Pain interference (HIV ß=-0.645, p<0.001, BC ß=-0.491, p<0.001) and age (HIV ß=-0.016, p=0.042 and BC ß=-0.018, p=0.019) associated with PHrQoL in both groups, and catastrophizing in the BC group (ß=-0.303, p<0.001). CONCLUSIONS: HIV patients and BC survivors with neuropathic pain, measured with DN4i, have significant differences in various health-related variables and Health-related Quality of Life with both patient groups reporting low HrQoL. The differences in low HrQoL may reflect the fundamental differences between these diseases, BC survivors in remission and HIV patients living with a chronic disease that is under control. This study brings information about the diversity of different patient populations with symptoms of neuropathic pain, and how neuropathic pain associates with wide range of health-related factors. Interventions to support better coping with the symptoms of neuropathic pain could be tailored more individually if the background disease is taken into account.

Psychological resilience associates with pain experience in women treated for breast cancer.

Background and aims Psychological resilience refers to successful adaptation or a positive outcome in the context of significant life adversity, such as chronic pain. On the other hand, anxiety closely associates with pain. The aim of this study was to explore how anxiety and psychological resilience together associate with persistent and experimental pain. Methods In a cross-sectional design, we studied 160 patients who had previously been treated for breast cancer and who now reported at least moderate pain (NRS ≥ 4) in any area of the body. Psychological resilience was measured on the Resilience Scale-14, anxiety on the Hospital Anxiety and Depression Scale, and intensity and interference of persistent pain by means of the Brief Pain Inventory. The cold pressor test was conducted to assess sensitivity to experimental cold pain. Results The results showed that resilience associated with pain interference in persistent pain, and that anxiety moderated this effect. Higher psychological resilience was associated with lower pain interference and this association was stronger in patients with low anxiety than among patients with high anxiety. These effects were visible with regard to persistent pain but not in experimental cold pain. Conclusions These results indicate that chronic pain and experimental pain as well as pain severity and pain interference are psychologically different phenomena. Psychological resilience protects against pain interference but effectively only in patients with low anxiety. It is necessary also to consider protective factors in addition to vulnerability factors in cases of persistent pain. Implications Resilience has been considered a potential target for intervention in chronic pain. However, high levels of anxiety might diminish the protective effect of psychological resilience in clinical settings. Therefore, it is important to treat anxiety in addition to resilience enhancing interventions. Patients with low psychological distress might be more suitable for resilience enhancing interventions than patients with high anxiety.

Machine-learned identification of psychological subgroups with relation to pain interference in patients after breast cancer treatments.

BACKGROUND: Persistent pain in breast cancer survivors is common. Psychological and sleep-related factors modulate perception, interpretation and coping with pain and may contribute to the clinical phenotype. The present analysis pursued the hypothesis that breast cancer survivors form subgroups, based on psychological and sleep-related parameters that are relevant to the impact of pain on the patients' life. METHODS: We analysed 337 women treated for breast cancer, in whom psychological and sleep-related parameters as well as parameters related to pain intensity and interference had been acquired. Data were analysed by using supervised and unsupervised machine-learning techniques (i) to detect patient subgroups based on the pattern of psychological or sleep-related parameters, (ii) to interpret the detected cluster structure and (iii) to relate this data structure to pain interference and impact on life. RESULTS: Artificial intelligence-based detection of data structure, implemented as self-organizing neuronal maps, identified two different clusters of patients. A smaller cluster (11.5% of the patients) had comparatively lower resilience, more depressive symptoms and lower extraversion than the other patients. In these patients, life-satisfaction, mood, and life in general were comparatively more impeded by persistent pain. CONCLUSIONS: The results support the initial hypothesis that psychological and sleep-related parameter patterns are meaningful for subgrouping patients with respect to how persistent pain after breast cancer treatments interferes with their life. This indicates that management of pain should address more complex features than just pain intensity. Artificial intelligence is a useful tool in the identification of subgroups of patients based on psychological factors.

The relationship between anger regulation, mood, pain, and pain-related disability in women treated for breast cancer.

OBJECTIVE: Anger, depressive symptoms, and anxiety are known reactions to cancer and suggested to modulate pain experience. We examined the association between anger regulation, mood, and pain in 952 breast cancer patients followed for 3 years. METHODS: Preoperatively, the patients completed questionnaires about depressive symptoms (BDI), state anxiety (STAI), anger regulation (STAXI-2), and pains in the surgical and other areas. Experimental pain sensitivity was tested. In the follow-up, BDI and STAI were assessed at 1 and at 6 months and at 1, 2, and 3 years after surgery. Pain in the surgical area was evaluated during the first 7 days and at 1 and 3 years after surgery. Pain-related disability was assessed at 3 years after surgery. Latent profile analyses were performed to identify mood profiles, and regression analyses to find independent predictors for mood and pain variables. RESULTS: Anger inhibition and pain had associations with ongoing depressive symptoms and anxiety. Pain-related disability was associated with high anxiety at a hazard ratio (HR) of 2.24 (95% CI, 1.17-4.27), with older age (HR 1.07, 95% CI, 1.01-1.13), and with pain in the surgical area (HR 3.04, 95% CI, 2.41-3.85), but not with anger variables. Any relationship between anger regulation and pain intensity disappeared after controlling for age and mood. CONCLUSIONS: Different forms of pain are important to recognize and treat to support breast cancer patients' psychological well-being. Anger inhibition could be a target for psychotherapeutic intervention, to help with ongoing mood symptoms. The relationship between anger regulation and pain is not straightforward.

What makes surgical nerve injury painful? A 4-year to 9-year follow-up of patients with intercostobrachial nerve resection in women treated for breast cancer.

Nerve injury during breast cancer surgery can cause neuropathic pain (NP). It is not known why some, but not all, patients develop chronic postsurgical neuropathic pain (CPSNP) after the same nerve injury. In this study, we examined 251 breast cancer survivors with surgeon-verified intercostobrachial nerve resection to identify factors that associate with CPSNP. The patients were recruited from a previous study of 1000 women treated for breast cancer in 2006 to 2010. This enabled us to analyze preoperative factors that associate with future CPSNP. The patients were re-examined in 2014 to 2016 to diagnose CPSNP using the revised NP diagnostic criteria. Preoperative assessments were pain in the area to be operated on, any chronic pain condition, depressive symptoms, anxiety, sleep, and experimental cold pain sensitivity using the cold pressor test (CPT). Follow-up assessments were CPT, psychological factors, sleep, any chronic pain, and basic laboratory tests. One hundred thirty-seven (55%) patients with intercostobrachial nerve resection fulfilled CPSNP diagnostic criteria after 4 to 9 years. Of them, 30 patients (22%) had moderate to severe pain in self-reports and 86 (63%) presented moderate to severe evoked pain at examination. Preoperative pain in the surgical area, other chronic pains, and breast-conserving surgery were associated with future CPSNP. Other chronic pains, increased psychological burden, and insomnia, both before surgery and at the follow-up, were associated with CPSNP. Preoperative CPT did not associate with future CPSNP. Patients with established CPSNP showed increased pain sensitivity in CPT and higher levels of inflammatory markers, suggesting that central sensitization and inflammation may associate with the maintenance of CPSNP.

Machine-learning-derived classifier predicts absence of persistent pain after breast cancer surgery with high accuracy.

BACKGROUND: Prevention of persistent pain following breast cancer surgery, via early identification of patients at high risk, is a clinical need. Supervised machine-learning was used to identify parameters that predict persistence of significant pain. METHODS: Over 500 demographic, clinical and psychological parameters were acquired up to 6 months after surgery from 1,000 women (aged 28-75 years) who were treated for breast cancer. Pain was assessed using an 11-point numerical rating scale before surgery and at months 1, 6, 12, 24, and 36. The ratings at months 12, 24, and 36 were used to allocate patents to either "persisting pain" or "non-persisting pain" groups. Unsupervised machine learning was applied to map the parameters to these diagnoses. RESULTS: A symbolic rule-based classifier tool was created that comprised 21 single or aggregated parameters, including demographic features, psychological and pain-related parameters, forming a questionnaire with "yes/no" items (decision rules). If at least 10 of the 21 rules applied, persisting pain was predicted at a cross-validated accuracy of 86% and a negative predictive value of approximately 95%. CONCLUSIONS: The present machine-learned analysis showed that, even with a large set of parameters acquired from a large cohort, early identification of these patients is only partly successful. This indicates that more parameters are needed for accurate prediction of persisting pain. However, with the current parameters it is possible, with a certainty of almost 95%, to exclude the possibility of persistent pain developing in a woman being treated for breast cancer.

Clinical Prediction Model and Tool for Assessing Risk of Persistent Pain After Breast Cancer Surgery.

Purpose Persistent pain after breast cancer surgery is a well-recognized problem, with moderate to severe pain affecting 15% to 20% of women at 1 year from surgery. Several risk factors for persistent pain have been recognized, but tools to identify high-risk patients and preventive interventions are missing. The aim was to develop a clinically applicable risk prediction tool. Methods The prediction models were developed and tested using three prospective data sets from Finland (n = 860), Denmark (n = 453), and Scotland (n = 231). Prediction models for persistent pain of moderate to severe intensity at 1 year postoperatively were developed by logistic regression analyses in the Finnish patient cohort. The models were tested in two independent cohorts from Denmark and Scotland by assessing the areas under the receiver operating characteristics curves (ROC-AUCs). The outcome variable was moderate to severe persistent pain at 1 year from surgery in the Finnish and Danish cohorts and at 9 months in the Scottish cohort. Results Moderate to severe persistent pain occurred in 13.5%, 13.9%, and 20.3% of the patients in the three studies, respectively. Preoperative pain in the operative area ( P < .001), high body mass index ( P = .039), axillary lymph node dissection ( P = .008), and more severe acute postoperative pain intensity at the seventh postoperative day ( P = .003) predicted persistent pain in the final prediction model, which performed well in the Danish (ROC-AUC, 0.739) and Scottish (ROC-AUC, 0.740) cohorts. At the 20% risk level, the model had 32.8% and 47.4% sensitivity and 94.4% and 82.4% specificity in the Danish and Scottish cohorts, respectively. Conclusion Our validated prediction models and an online risk calculator provide clinicians and researchers with a simple tool to screen for patients at high risk of developing persistent pain after breast cancer surgery.

Does expecting more pain make it more intense? Factors associated with the first week pain trajectories after breast cancer surgery.

The aim of this study was to identify clinical risk factors for unfavorable pain trajectories after breast cancer surgery, to better understand the association between pain expectation, psychological distress, and acute postoperative pain. This prospective study included 563 women treated for breast cancer. Psychological data included questionnaires for depressive symptoms and anxiety. Experimental pain tests for heat and cold were performed before surgery. The amount of oxycodone needed for satisfactory pain relief after surgery was recorded. Pain intensity in the area of operation before surgery and during the first postoperative week and expected intensity of postoperative pain were recorded using the Numerical Rating Scale (NRS 0-10). Pain trajectories were formed to describe both initial intensity (the intercept) and the direction of the pain path (the slope). Factors associated with higher initial pain intensity (the intercept) were the amount of oxycodone needed for adequate analgesia, psychological distress, type of axillary surgery, preoperative pain in the area of the operation, and expectation of postoperative pain. The higher the pain initially was, the faster it resolved over the week. Expectation of severe postoperative pain was associated with higher scores of both experimental and clinical pain intensity and psychological factors. The results confirm that acute pain after breast cancer surgery is a multidimensional phenomenon. Psychological distress, pain expectation, and the patients' report of preoperative pain in the area to be operated should be recognized before surgery. Patients having axillary clearance need more efficient analgesic approaches.

Pain in 1,000 women treated for breast cancer: a prospective study of pain sensitivity and postoperative pain.

BACKGROUND: This article describes the methods and results of the early part (experimental pain tests and postoperative analgesia) of a study that assesses genetic and other factors related to acute pain and persistent pain after treatment of breast cancer in a prospective cohort of 1,000 women. METHODS: One thousand consenting patients were recruited to the study. Before surgery (breast resection or mastectomy with axillary surgery), the patients filled in questionnaires about health, life style, depression (Beck Depression Inventory), and anxiety (State-Trait Anxiety Inventory). They were also exposed to experimental tests measuring heat (43° and 48°C, 5 s) and cold (2-4°C) pain intensity and tolerance. Anesthesia was standardized with propofol and remifentanil, and postoperative analgesia was optimized with i.v. oxycodone. RESULTS: The patients showed significant interindividual variation in heat and cold pain sensitivity and cold pain tolerance. There was a strong correlation between the experimental pain measures across the tests. Presence of chronic pain, the number of previous operations, and particularly state anxiety were related to increased pain sensitivity. Previous smoking correlated with decreased heat pain sensitivity. These factors explained 4-5% of the total variance in pain sensitivity in these tests. Oxycodone consumption during 20 h was significantly higher in patients who had axillary clearance. Oxycodone consumption had only a weak correlation with the experimental pain measures. CONCLUSIONS: Contact heat and cold pressure tests identify variability in pain sensitivity which is modified by factors such as anxiety, chronic pain, previous surgery, and smoking. High levels of anxiety are connected to increased pain sensitivity in experimental and acute postoperative pain.