An overview of a biopsychosocial model of epigenetics and pain catastrophizing

The objective of the present study was to establish the heritability of pain catastrophizing and its subdomains of helplessness, magnification, and rumination and to further explore the genetic and environmental sources that may contribute to pain catastrophizing as well as to its commonly reported psycho-affective correlates, including neuroticism, anxiety sensitivity, and fear of pain. N = 2,401 female twin individuals from the TwinsUK registry were subject to univariate and multivariate twin analyses. Well validated questionnaires including the Pain Catastrophizing Scale, the Pain Anxiety Symptom Scale, the Ten Item Personality Index, and the Anxiety Sensitivity Index were used to assess the study variables. Moderate estimates of heritability for pain catastrophizing (36%) and the three subdomains of helplessness (35%), rumination (27%), and magnification (36%) were detected. The high correlations observed between the three subdomains were explained mainly by overlapping genetic factors, with a single factor loading on all three phenotypes. High genetic correlations between pain catastrophizing and its psycho-affective correlates of fear of pain and anxiety sensitivity were found, while the genetic overlap between neuroticism and pain catastrophizing was low. Each measure of negative affect demonstrated relatively distinct environmental contributing factors, with very little overlap. This is the first study to show shared genetic factors in the observed association between pain catastrophizing and other measures of negative affect. Our findings provide deeper insight into the aetiology of pain catastrophizing and confirm that it is at least partially distinct from other measures of negative affect and personality that may influence the development and treatment of chronic pain conditions. Further research in males is warranted to check the comparability of the findings.

Psychologic influence on experimental pain sensitivity and clinical pain intensity for patients with shoulder pain.

Although a few studies have delineated the disparities in knee osteoarthritis (KOA) pain between non-Hispanic White and Asian American individuals, a significant research gap persists in elucidating the mechanisms underlying these differences. This pilot study aims to examine psychological factors, specifically pain catastrophizing and negative affect, as potential explanatory mechanisms for these dissimilarities. A cross-sectional design was used. Forty community-dwelling participants aged 50-70 years with self-reported KOA pain, including 20 non-Hispanic White and 20 Asian American individuals, were recruited in North Central Florida. Clinical KOA pain intensity was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the 4 subscales of the Short-Form McGill Pain Questionnaire-2. Quantitative sensory testing was conducted to measure experimental sensitivity to heat- and mechanically induced pain, including heat pain, pressure pain threshold, and punctate mechanical pain, as well as inhibitory pain processes through conditioned pain modulation. Pain catastrophizing was evaluated using the Coping Strategies Questionnaire-Revised Pain Catastrophizing subscale, while negative affect was assessed using the Positive and Negative Affect Schedule. Bayesian mediation analyses were used to examine both direct and indirect effects (mediation) between variables. Asian American individuals exhibited higher pain catastrophizing scores than non-Hispanic White individuals. Pain catastrophizing, at high levels, contributed to WOMAC and Short-Form McGill Pain Questionnaire-2, which measured clinical pain. Race had no direct effects on these pain scores but exerted significant indirect effects via pain catastrophizing (WOMAC pain: 0.96, 95% CI 0.03-2.16; continuous pain: 0.84, 95% CI 0.18-1.70; intermittent pain: 0.78, 95% CI 0.03-1.71; neuropathic pain: 0.43, 95% CI 0.03-0.95; and affective pain: 1.05, 95% CI 0.24-1.99); thus, pain catastrophizing likely fully mediated the relationship between race and these pain measures. While Asian American individuals reported greater experimental pain sensitivity (heat pain, pressure pain threshold, and punctate mechanical pain) than non-Hispanic White individuals, these racial effects were not mediated by pain catastrophizing. Asian American individuals reported higher negative affect scores compared with non-Hispanic White individuals; however, negative affect did not mediate the relationship between race and any pain measures. The results demonstrate the contribution of pain catastrophizing to clinical pain in Asian American individuals with KOA and identify it as a potential mechanism underlying group differences in KOA pain between non-Hispanic White and Asian American individuals. However, caution is warranted due to the exploratory nature of this study and the treatment of Asian American individuals as a monolithic sample. Hence, future replication with larger and more diverse samples is necessary. Additionally, the lack of mediation effects of pain catastrophizing in the relationship between race and experimental pain suggests the need to explore other factors, such as biological, genetic, social, and environmental influences. Moreover, further research is essential to clarify the role of negative affect.

Total hip replacement (THR) is the definitive treatment for degenerative conditions of the hip with an excellent track record for success. However, there is emerging evidence that patients with musculoskeletal conditions suffering from concomitant psychological and/or mental health ailments may be predisposed to suboptimal outcomes after surgery. Determining whether psychological and mental health influence outcomes following Total Hip Replacement (THR)—and to what extent—has important prognostic, preventive, and therapeutic implications. In this study, we evaluated the influence of pre-operative pain catastrophizing, depression, and/or mental health on post-operative clinical outcomes following THR. We evaluated outcomes as part of a secondary analysis in a prospective cohort observational study of patients undergoing THR. We employed a multivariable mixed model regression analysis to determine whether pain catastrophizing, depression, or mental health was associated with persistent pain, decreased function, and/or higher risk of revision surgery pre-operatively and up to 5 years post-operatively. A Pain Catastrophizing Scale (PCS) score of 30 or above was pre-defined as the threshold for clinically important pain catastrophizing. Depression and mental health were reported and analyzed as binary categorical variables. We used the ICOAP to measure constant and intermittent hip pain and the WOMAC Physical Function measure to measure physical function. A p value of less than 0.05 was considered as statistically significant. The study cohort consisted of 576 patients who underwent THR (49.3% male; 50.7% female), divided into 189 who screened positive for a psychological, mental health, or pain catastrophizing and 387 who did not. All patients improved substantially following THR, with large significant and clinically important improvements between pre-operative and all post-operative follow up time points for both groups. After adjustment, constant pain scores (ICOAP Constant) were 1.35 (SE 0.18) higher in those with a PCS score >= 30 (p = 30. Female sex was also significantly associated with higher pain scores. Physical function scores (WOMAC PF) were 4.61 (SE 0.53) higher (i.e. worse) in those with PCS > = 30. Younger age at surgery and female sex were also associated with higher WOMAC PF scores (i.e. worse function). History of depression or mental health disorder were not significant in the model. Patients with high levels of pain catastrophizing show large improvements in pain and function following THR. However, these patients have higher levels of pre-operative and post-operative pain and lower physical function following THR. Although the differences are small, pain catastrophizing may be used as one element of a risk stratification model to estimate risk of poor post-operative outcome following THR. Whether targeted interventions to address pain catastrophizing can improve surgical outcome remains to be investigated.

Trait mindfulness and catastrophizing as mediators of the association between pain severity and pain-related impairment

Pain catastrophizing, a coping style characterized by excessively negative thoughts and emotions in relation to pain, is one of the psychological factors that most markedly predicts variability in the perception of pain; however, only little is known about the underlying neurobiology. The aim of this study was to test for associations between psychological variables, such as pain catastrophizing, anxiety and depression, and selected polymorphisms in genes related to monoaminergic neurotransmission, in particular serotonin pathway genes. Three hundred seventy-nine healthy participants completed a set of psychological questionnaires: the Pain Catastrophizing Scale (PCS), the State-Trait Anxiety Inventory and Beck’s Depression Inventory, and were genotyped for 15 single nucleotide polymorphisms (SNPs) in nine genes. The SNP rs1176744 located in the serotonin receptor 3B gene (5-HTR3B) was found to be associated with pain catastrophizing scores: both the global score and the subscales of magnification and helplessness. This is the first study to show an association between 5-HTR3B and PCS scores, thus suggesting a role of the serotonin pathway in pain catastrophizing. Since 5-HTR3B has previously been associated with descending pain modulation pathways, future studies will be of great interest to elucidate the molecular pathways involved in the relation between serotonin, its receptors and pain catastrophizing.

Psychological factors are linked to pain and function in various musculoskeletal conditions, but their impact on hallux valgus is unclear. Health-related quality of life declines with increasing severity of hallux valgus, affecting not only foot pain and physical function, but also general health, vitality and mental health. Previous studies have reported inconsistent associations between psychological factors, such as anxiety and depression, and surgical outcomes, which might relate to variability in measurement approaches. Understanding the associations between psychological factors, including anxiety, depression, pain catastrophizing and kinesiophobia, and hallux valgus-related pain and function may inform more holistic pre-operative care. Therefore, we aimed to assess these associations in adults with hallux valgus pre-surgery. A pre-operative cross-sectional study was conducted with 41 adults scheduled for hallux valgus surgery. Participants completed questionnaires measuring continuous psychological variables: depression, anxiety and stress (Depression Anxiety Stress Scale-21, a tool for general psychological distress), kinesiophobia (Tampa Scale for Kinesiophobia, which assesses fear of movement associated with pain) and pain catastrophizing (Pain Catastrophizing Scale, a tool used to evaluate maladaptive pain-coping strategies). Continuous outcomes were evaluated using the Manchester-Oxford Foot Questionnaire for foot function, pain and social interaction. Multiple linear regressions explored the associations between these psychological factors and the outcomes. When all exposure variables were considered simultaneously, pain catastrophizing emerged as a significant predictor of foot pain and foot function. A one-unit increase in the pain catastrophizing score was associated with a 1.41-point increase in foot pain (β=1.41, 95% confidence intervals (CIs) 0.73-2.09 and p<0.001) and a 1.83-point increase in worse foot function (β=1.83, 95% CI 1.12-2.54 and p<0.001). Assessing pain catastrophising pre-operatively is recommended for individuals with hallux valgus, although more structured education may be needed to support health professionals in assessing psychological factors. Future research should evaluate the longitudinal impact of pain catastrophizing on post-operative outcomes and explore other contributing factors, such as comorbidities, lifestyle variables and sex differences, to refine screening and treatment strategies.

Adult attachment and pain catastrophizing for self and significant other

Evidence for a biopsychosocial influence on shoulder pain: Pain catastrophizing and catechol- O-methyltransferase (COMT) diplotype predict clinical pain ratings

The present study compared psychological factors (i.e., alexithymia, somatization, pain catastrophizing (PC), anxiety, and depression) and QOL for headache patients and headache-free individuals, and examined whether somatization and PC mediate the relationship between alexithymia and headache impact in headache patients. Study participants consisted of 123 headache patients from an outpatient clinic at a university hospital and 124 headache-free individuals in Daegu, Korea. The survey employed the somatization and anxiety subscales of the Symptom Checklist-90-revised, the Patient Health Questionnaire-9, Pain Catastrophizing Scale, Toronto Alexithymia Scale, Short-Form Health survey-8 (SF-8), and the Headache Impact Test-6. Headache patients showed a higher level of all psychological factors and lower level of two summary scores (physical and mental health) as well as the seven dimensions of the SF-8 compared with headache-free individuals. Examination employing the SPSS Process macro found that the direct effect of alexithymia on headache impact was not significant after controlling for somatization and PC. The total indirect effects of alexithymia on headache impact were significant without anxiety and depression as covariates with the significant indirect effects of alexithymia on headache impact via somatization or via PC as well as via somatization and PC. However, after controlling for anxiety and depression, PC was the only significant pathway through which alexithymia was related to headache impact. Headache patients may benefit from interventions aiming at improving psychological factors in order to improve the functioning and QOL of headache patients.

The experience of pain is believed to be influenced by psychologic and genetic factors. A previous study suggested pain catastrophizing and catechol-O-methyltransferase (COMT) genotype influenced clinical pain ratings for patients seeking operative treatment of shoulder pain. This study investigated whether these same psychologic and genetic factors predicted responses to induced shoulder pain. Participants (n=63) completed self-report questionnaires and had COMT genotype determined before performing a standardized fatigue protocol to induce delayed onset muscle soreness. Then, shoulder pain ratings, self-report of upper-extremity disability ratings, and muscle torque production were reassessed 24, 48, and 72 hours later. This cohort consisted of 35 women and 28 men, with a mean age of 20.9 years (SD=1.7). The frequency of COMT diplotypes was 42 with "high COMT enzyme activity" (low pain sensitivity group) and 21 with "low COMT enzyme activity" (average pain sensitivity/high pain sensitivity group). A hierarchical regression model indicated that an interaction between pain catastrophizing and COMT diplotype was the strongest unique predictor of 72-hour pain ratings. The same interaction was not predictive of self-report of disability or muscle torque production at 72 hours. The pain catastrophizingxCOMT diplotype interaction indicated that participants with high pain catastrophizing and low COMT enzyme activity (average pain sensitivity/high pain sensitivity group) were more likely (relative risk=3.5, P=0.025) to have elevated pain intensity ratings (40/100 or higher). These findings from an experimental model converge with those from a surgical cohort and provide additional evidence that the presence of elevated pain catastrophizing and COMT diplotype indicative of low COMT enzyme activity have the potential to increase the risk of developing chronic pain syndromes.

Increased Pain Variability in Patients With Chronic Pain: A Role for Pain Catastrophizing

Biopsychosocial Influence on Exercise-Induced Injury: Genetic and Psychological Combinations Are Predictive of Shoulder Pain Phenotypes

To conduct a systematic review of pain anxiety, pain catastrophizing, and fear of pain measures psychometrically established in youth with chronic pain. The review addresses three specific aims: (1) to identify measures used in youth with chronic pain, summarizing their content, psychometric properties, and use; (2) to use evidence-based assessment criteria to rate each measure according to the Society of Pediatric Psychology (SPP) guidelines; (3) to pool data across studies for meta-analysis of shared variance in psychometric performance in relation to the primary outcomes of pain intensity, disability, generalized anxiety, and depression. We searched Medline, Embase, PsycINFO, and relevant literature for possible studies to include. We identified measures studied in youth with chronic pain that assessed pain anxiety, pain catastrophizing, or fear of pain and extracted the item-level content. Study and participant characteristics, and correlation data were extracted for summary and meta-analysis, and measures were rated using the SPP evidence-based assessment criteria. Fifty-four studies (84 papers) met the inclusion criteria, including seven relevant measures: one assessed pain anxiety, three pain catastrophizing, and three fear of pain. Overall, five measures were rated as "well established." We conducted meta-analyses on four measures with available data. We found significant positive correlations with the variables pain intensity, disability, generalized anxiety, and depression. Seven measures are available to assess pain anxiety, pain catastrophizing, and fear of pain in young people with chronic pain, and most are well established. We present implications for practice and directions for future research.

BackgroundTotal knee arthroplasty (TKA) is a common and costly surgical procedure. Despite high success rates, many TKA patients develop chronic pain in the months and years following surgery, constituting a public health burden. Pain catastrophizing is a construct that reflects anxious preoccupation with pain, inability to inhibit pain-related fears, amplification of the significance of pain vis-à-vis health implications, and a sense of helplessness regarding pain. Recent research suggests that it may be an important risk factor for untoward TKA outcomes. To clarify this impact, we systematically reviewed the literature to date on pain catastrophizing as a prospective predictor of chronic pain following TKA.MethodsWe searched MEDLINE, EMBASE, and PsycINFO databases to identify articles related to pain catastrophizing, TKA, risk models, and chronic pain. We reviewed titles and abstracts to identify original research articles that met our specified inclusion criteria. Included articles were then rated for methodological quality. including methodological quality. Due to heterogeneity in follow-up, analyses, and outcomes reported across studies, a quantitative meta-analysis could not be performed.ResultsWe identified six prospective longitudinal studies with small-to-mid-sized samples that met the inclusion criteria. Despite considerable variability in reported pain outcomes, pain catastrophizing was identified as a significant predictor of chronic pain persisting ≥3 months following TKA in five of the studies assessed. Limitations of studies included lack of large-scale data, absence of standardized pain measurements, inadequate multivariate adjustment, such as failure to control for analgesic use and other relevant covariates, and failure to report non-significant parameter estimates.ConclusionThis study provides moderate-level evidence for pain catastrophizing as an independent predictor of chronic pain post-TKA. Directions for future research include larger, well-controlled studies with standard pain outcomes, identification of clinically-relevant catastrophizing cut-offs that predict pain outcomes, investigation of other psychosocial risk factors, and assessment of interventions aimed to reduce pain catastrophizing on chronic pain outcomes following TKA surgery.