Resting-state brain activity as a biomarker of chronic pain impairment and a mediator of its association with pain resilience.

Past cross-sectional chronic pain studies have revealed aberrant resting-state brain activity in regions involved in pain processing and affect regulation. However, there is a paucity of longitudinal research examining links of resting-state activity and pain resilience with changes in chronic pain outcomes over time. In this prospective study, we assessed the status of baseline (T1) resting-state brain activity as a biomarker of later impairment from chronic pain and a mediator of the relation between pain resilience and impairment at follow-up. One hundred forty-two adults with chronic musculoskeletal pain completed a T1 assessment comprising a resting-state functional magnetic resonance imaging scan based on regional homogeneity (ReHo) and self-report measures of demographics, pain characteristics, psychological status, pain resilience, pain severity, and pain impairment. Subsequently, pain impairment was reassessed at a 6-month follow-up (T2). Hierarchical multiple regression and mediation analyses assessed relations of T1 ReHo and pain resilience scores with changes in pain impairment. Higher T1 ReHo values in the right caudate nucleus were associated with increased pain impairment at T2, after controlling for all other statistically significant self-report measures. ReHo also partially mediated associations of T1 pain resilience dimensions with T2 pain impairment. T1 right caudate nucleus ReHo emerged as a possible biomarker of later impairment from chronic musculoskeletal pain and a neural mechanism that may help to explain why pain resilience is related to lower levels of later chronic pain impairment. Findings provide empirical foundations for prospective extensions that assess the status of ReHo activity and self-reported pain resilience as markers for later impairment from chronic pain and targets for interventions to reduce impairment. PRACTITIONER POINTS: Resting-state markers of impairment: Higher baseline (T1) regional homogeneity (ReHo) values, localized in the right caudate nucleus, were associated with exacerbations in impairment from chronic musculoskeletal pain at a 6-month follow-up, independent of T1 demographics, pain experiences, and psychological factors. Mediating role of ReHo values: ReHo values in the right caudate nucleus also mediated the relationship between baseline pain resilience levels and later pain impairment among participants. Therapeutic implications: Findings provide empirical foundations for research extensions that evaluate (1) the use of resting-state activity in assessment to identify people at risk for later impairment from pain and (2) changes in resting-state activity as biomarkers for the efficacy of treatments designed to improve resilience and reduce impairment among those in need.

Investigating mortality salience as a potential causal influence and moderator of responses to laboratory pain.

Background: Because pain can have profound ramifications for quality of life and daily functioning, understanding nuances in the interplay of psychosocial experiences with pain perception is vital for effective pain management. In separate lines of research, pain resilience and mortality salience have emerged as potentially important psychological correlates of reduced pain severity and increased tolerance of pain. However, to date, there has been a paucity of research examining potentially interactive effects of these factors on pain perception. To address this gap, the present experiment investigated mortality salience as a causal influence on tolerance of laboratory pain and a moderator of associations between pain resilience and pain tolerance within a Chinese sample. Methods: Participants were healthy young Chinese adults (86 women, 84 men) who first completed a brief initial cold pressor test (CPT) followed by measures of demographics and pain resilience. Subsequently, participants randomly assigned to a mortality salience (MS) condition completed two open-ended essay questions in which they wrote about their death as well as a death anxiety scale while those randomly assigned to a control condition completed analogous tasks about watching television. Finally, all participants engaged in a delay task and a second CPT designed to measure post-manipulation pain tolerance and subjective pain intensity levels. Results: MS condition cohorts showed greater pain tolerance than controls on the post-manipulation CPT, though pain intensity levels did not differ between groups. Moderator analyses indicated that the relationship between the behavior perseverance facet of pain resilience and pain tolerance was significantly stronger among MS condition participants than controls. Conclusions: This experiment is the first to document potential causal effects of MS on pain tolerance and Ms as a moderator of the association between self-reported behavior perseverance and behavioral pain tolerance. Findings provide foundations for extensions within clinical pain samples.

Mechanisms of change in depression and anxiety within a mind-body activity intervention for chronic pain.

BACKGROUND: Chronic pain is challenging and costly to treat. Depression and anxiety co-occur with chronic pain. Identifying psychosocial mechanisms contributing to emotional outcomes among chronic pain patients can inform future iterations of this intervention. METHODS: We examined explanatory mechanisms of change in emotional distress following a mind-body and activity intervention among 82 participants (21 - 79 years old, 65.85% female, 80.48% White). With depression and anxiety as outcomes, we hypothesized that potential mediators would include pain catastrophizing, mindfulness, and pain resilience. We used mixed-effects modeling to assess the indirect effects of time on each outcome variable through hypothesized mediators simultaneously. RESULTS: Improvements in depression from baseline to post-treatment were most explained by pain catastrophizing (b = -2.53, CI = [-3.82, -1.43]), followed by mindfulness (b = -1.21, CI = [-2.15, -0.46]), and pain resilience (b = -0.76, CI = [-1.54, -1.66]). Improvements in anxiety from baseline to post-treatment were most explained by pain catastrophizing(b = -2.16, CI = [-3.45, -1.08]) and mindfulness (b = -1.51, CI = [-2.60, -0.65]), but not by pain resilience, (b = -0.47, CI = [-1.26, 0.17]). LIMITATIONS: Findings are limited by the lack of a control group, relatively small sample, and two timepoints. However, findings can guide future mind-body intervention efficacy testing trials. CONCLUSIONS: Pain catastrophizing and mindfulness appear to be important intervention targets to enhance emotional functioning for chronic pain patients, and should be considered simultaneously in interventions for chronic pain.

Associations of Regional and Network Functional Connectivity With Exercise-Induced Low Back Pain.

Musculoskeletal pain is an aversive experience that exists within a variety of conditions and can result in significant impairment for individuals. Gaining greater understanding of the factors related to pain vulnerability and resilience to musculoskeletal pain may help target at-risk individuals for early intervention. This analysis builds on our previous work identifying regions where greater gray matter density was associated with lower pain following standardized, exercise induced musculoskeletal injury. Here we sought to examine the relationship between baseline resting state functional connectivity in a priori regions and networks, and delayed onset muscle soreness (DOMS) pain intensity following a single session of eccentric exercise in healthy adults. Participants completed a baseline functional MRI scan and a high intensity trunk exercise protocol in the erector spinae. Pain intensity ratings were collected 48-hours later. Resting state functional connectivity from four seed regions and 3 networks were separately regressed on pain intensity scores. Results revealed that connectivity between left middle frontal gyrus, the left occipital gyrus and cerebellar network seeds and clusters associated with discriminative, emotional, and cognitive aspects of pain were associated with lower post-DOMS pain. Results suggest resilience to clinically relevant pain is associated with aspects of regional and network neural coherence. Investigations of pain modulatory capacity that integrate multimodal neuroimaging metrics are called for. PERSPECTIVE: Our results provide key support for the role of structural and functional coherence in regional and network connectivity in adaptive pain response and represent an important step in clarifying neural mechanisms of resilience to clinically relevant pain.

Gray Matter Volume Differences Between More Versus Less Resilient Adults with Chronic Musculoskeletal Pain: A Voxel-based Morphology Study.

Resilience, a personality construct that reflects capacities to persevere, maintain a positive outlook and/or thrive despite ongoing stressors, has emerged as an important focus of research on chronic pain (CP). Although behavior studies have found more resilient persons with CP experience less pain-related dysfunction than less resilient cohorts do, the presence and nature of associated brain structure differences has received scant attention. To address this gap, we examined gray matter volume (GMV) differences between more versus less resilient adults with chronic musculoskeletal pain. Participants (75 women, 43 men) were community-dwellers who reported ongoing musculoskeletal pain for at least three months. More (n = 57) and less (n = 61) resilient subgroups, respectively, were identified on the basis of scoring above and below median scores on two validated resilience questionnaires. Voxel-based morphology (VBM) undertaken to examine resilience subgroup differences in GMV indicated more resilient participants displayed significantly larger GMV in the (1) bilateral precuneus, (2) left superior and inferior parietal lobules, (3) orbital right middle frontal gyrus and medial right superior frontal gyrus, and (4) bilateral median cingulate and paracingulate gyri, even after controlling for subgroup differences on demographics and measures of pain-related distress. Together, results underscored the presence and nature of specific GMV differences underlying subjective reports of more versus less resilient responses to ongoing musculoskeletal pain.

Pain resilience, pain catastrophizing, and executive functioning: performance on a short-term memory task during simultaneous ischemic pain.

Among pain researchers there is a growing interest in the relationship between psychological resilience and pain experience. Whereas much of this work has focused on individual differences in pain perception or sensitivity, an equally important dimension of resilience is the capacity to persist with goal-directed activity despite experiencing pain. Consistent with this latter focus, the current study examined how pain resilience and pain catastrophizing combine to moderate the effects of ischemic pain on short-term memory task performance. Using a within-subjects design, 121 healthy participants completed four trials of a Corsi block-tapping task with pain exposure during the second and fourth trials. Results indicated that a combination of high pain resilience and low pain catastrophizing was associated with better task performance during the second pain exposure. These findings confirm existing evidence that resilience can moderate performance during pain, and offer new evidence that resilience and catastrophizing interact to shape this effect.

Asymmetries in reciprocal baroreflex mechanisms and chronic pain severity: Focusing on irritable bowel syndrome.

BACKGROUND: Objective measures of pain severity remain ill defined, although its accurate measurement is critical. Reciprocal baroreflex mechanisms of blood pressure (BP) control were found to impact differently on pain regulation, and thus their asymmetry was hypothesized to also connect to chronic pain duration and severity. METHODS: Seventy-eight female patients with irritable bowel syndrome (IBS) and 27 healthy women were assessed for IBS severity and chronicity, negative affect, and various measures of resting autonomic function including BP, heart rate and its variability (HRV), baroreceptor-sensitivity to activations and inhibitions, gains of brady- and tachy-cardiac baro-responses, gains of BP falls/rises, and BP start points for these spontaneous baroreflexes. KEY RESULTS: IBS directly and indirectly (through increased negative affect) was associated with asymmetry between baroreceptor activations/inhibitions compared to symmetrical baroreflex reciprocity in the healthy women. In the IBS group, independently of specific IBS symptoms, pain chronicity was associated with (i) decreased BP falls coupled with either (a) decreased tachycardia associated with lower disease severity (earlier "pain resilience" mechanism), or (b) decreased bradycardia associated with higher disease severity (later "pain decompensation" mechanism), or (ii) increased BP start point for baroreceptor activations coupled with either (a) BP increase (delayed "pain adaptation" mechanism) or (b) affect-related HRV decrease (delayed "pain aggravation" mechanism). CONCLUSION AND INFERENCES: We anticipate the findings to be a starting point for validating these autonomic metrics of pain suffering and pain coping mechanisms in other chronic pain syndromes to suggest them as biomarkers of its severity and duration for profiling and correct management of chronic pain patients.

Validation of the Pain Resilience Scale in Chinese-speaking patients with temporomandibular disorders pain.

To validate the Pain Resilience Scale (PRS) for use in Chinese patients with temporomandibular disorders (TMD) pain. According to international guidelines, the original PRS was first translated and cross-culturally adapted to formulate the Chinese version of PRS (PRS-C). A total of 152 patients with TMD pain were recruited to complete series of questionnaires. Reliability of the PRS-C was investigated using internal consistency and test-retest reliability. Validity of the PRS-C was calculated using cross-cultural validity and convergent validity. Cross-cultural validity was evaluated by examining the confirmatory factor analysis (CFA). And convergent validity was examined through correlating the PRS-C scores with scores of 2 commonly used pain-related measures (the Connor-Davidson Resilience Scale [CD-RISC] and the Tampa Scale for Kinesiophobia for Temporomandibular Disorders [TSK-TMD]). The PRS-C had a high internal consistency (Cronbach's alpha = 0.92) and good test-retest reliability (intra-class correlation coefficient [ICC] = 0.81). The CFA supported a 2-factor model for the PRS-C with acceptable fit to the data. The fit indices were chi-square/DF = 2.21, GFI = 0.91, TLI = 0.97, CFI = 0.98 and RMSEA = 0.08. As regards convergent validity, the PRS-C evidenced moderate-to-good relationships with the CD-RISC and the TSK-TMD. The PRS-C shows good psychometric properties and could be considered as a reliable and valid measure to evaluate pain-related resilience in patients with TMD pain.

Psychometric evaluation of the Chinese version of the Pain Resilience Scale in patients with coronary heart disease / 中国实用护理杂志

Objective To translate the Pain Resilience Scale (PRS) into Chinese and evaluate its psychometric characteristics in patients with coronary heart disease with chest pain. Methods Convenience sampling was used to recruit 340 patients with coronary heart disease in Tianjin medical university general hospital. Results The content validity and criterion validity were 0.939 and 0.852 respectively. Through EFA ,the Chinese version of PRS included three dimension which accounted for 58.214% of the accumulated variance, and each item had high factor loading quantity (>0.5). CFA showed that the modified model fitted well. Cronbach alpha was 0.821 and the test-retest reliability was 0.911. Conclusions The Chinese version of PRS has been proved to be valid and reliable and can be used among patients with coronary heart disease with chest pain.

The effect of resilience on task persistence and performance during repeated exposure to heat pain.

The Pain Resilience Scale was recently developed to assess dimensions of resilience critical to pain-related adaptation and was found to predict experimental pain sensitivity in a pain-free population. Pain resilience has also been theoretically linked to behavioral persistence despite pain. To date, however, this hypothesis has not been experimentally tested. To address this gap in the literature, in the current study 105 healthy young adults underwent a baseline administration of the Paced Auditory Serial Addition Test (PASAT), a stressful mental arithmetic task, delivered with somatosensory distraction (i.e. detection of warm and cool thresholds), and finally simultaneous administration of the PASAT and a series of five heat pain threshold assessments. Results of hierarchical multiple linear regressions indicated that, after controlling for scores on a baseline PASAT and pain sensitivity, pain resilience was positively related to task persistence, B = 0.12, p = 0.04, and task performance, B = 0.14, p = 0.04, on the PASAT. These findings provide novel support for the relationship between pain resilience and behavioral perseverance.