Investigation of the Relationships among Self-Efficacy, Stress, and Dyspareunia during the COVID-19 Pandemic.

This study examined whether low self-efficacy and heightened perceived stress were associated with dyspareunia at two timepoints during COVID-19. Sixty-two participants (31 with and 31 without dyspareunia) completed a longitudinal online survey. Self-efficacy declined during the pandemic, and individuals with dyspareunia reported lower self-efficacy compared to those without dyspareunia. Although stress was greater for those with dyspareunia, both groups reported stress reductions over time. Lower stress was associated with increases in self-efficacy. This study is the first to examine longitudinal trends of dyspareunia during the COVID-19 pandemic and illuminates psychological factors that may influence the experience of dyspareunia.

The structural and functional connectivity neural underpinnings of body image.

How we perceive our bodies is fundamental to our self-consciousness and our experience in the world. There are two types of interrelated internal body representations-a subjective experience of the position of a limb in space (body schema) and the subjective experience of the shape and size of the limb (body image). Body schema has been extensively studied, but there is no evidence of the brain structure and network dynamics underpinning body image. Here, we provide the first evidence for the extrastriate body area (EBA), a multisensory brain area, as the structural and functional neural substrate for body shape and size. We performed a multisensory finger-stretch illusion that elongated the index finger. EBA volume and functional connectivity to the posterior parietal cortex are both related to the participants' susceptibility to the illusion. Taken together, these data suggest that EBA structure and connectivity encode body representation and body perception disturbances.

The integration of negative affect, pain and cognitive control in the cingulate cortex.

It has been argued that emotion, pain and cognitive control are functionally segregated in distinct subdivisions of the cingulate cortex. However, recent observations encourage a fundamentally different view. Imaging studies demonstrate that negative affect, pain and cognitive control activate an overlapping region of the dorsal cingulate--the anterior midcingulate cortex (aMCC). Anatomical studies reveal that the aMCC constitutes a hub where information about reinforcers can be linked to motor centres responsible for expressing affect and executing goal-directed behaviour. Computational modelling and other kinds of evidence suggest that this intimacy reflects control processes that are common to all three domains. These observations compel a reconsideration of the dorsal cingulate's contribution to negative affect and pain.

Discovering biomarkers for antidepressant response: protocol from the Canadian biomarker integration network in depression (CAN-BIND) and clinical characteristics of the first patient cohort.

BACKGROUND: Major Depressive Disorder (MDD) is among the most prevalent and disabling medical conditions worldwide. Identification of clinical and biological markers ("biomarkers") of treatment response could personalize clinical decisions and lead to better outcomes. This paper describes the aims, design, and methods of a discovery study of biomarkers in antidepressant treatment response, conducted by the Canadian Biomarker Integration Network in Depression (CAN-BIND). The CAN-BIND research program investigates and identifies biomarkers that help to predict outcomes in patients with MDD treated with antidepressant medication. The primary objective of this initial study (known as CAN-BIND-1) is to identify individual and integrated neuroimaging, electrophysiological, molecular, and clinical predictors of response to sequential antidepressant monotherapy and adjunctive therapy in MDD. METHODS: CAN-BIND-1 is a multisite initiative involving 6 academic health centres working collaboratively with other universities and research centres. In the 16-week protocol, patients with MDD are treated with a first-line antidepressant (escitalopram 10-20 mg/d) that, if clinically warranted after eight weeks, is augmented with an evidence-based, add-on medication (aripiprazole 2-10 mg/d). Comprehensive datasets are obtained using clinical rating scales; behavioural, dimensional, and functioning/quality of life measures; neurocognitive testing; genomic, genetic, and proteomic profiling from blood samples; combined structural and functional magnetic resonance imaging; and electroencephalography. De-identified data from all sites are aggregated within a secure neuroinformatics platform for data integration, management, storage, and analyses. Statistical analyses will include multivariate and machine-learning techniques to identify predictors, moderators, and mediators of treatment response. DISCUSSION: From June 2013 to February 2015, a cohort of 134 participants (85 outpatients with MDD and 49 healthy participants) has been evaluated at baseline. The clinical characteristics of this cohort are similar to other studies of MDD. Recruitment at all sites is ongoing to a target sample of 290 participants. CAN-BIND will identify biomarkers of treatment response in MDD through extensive clinical, molecular, and imaging assessments, in order to improve treatment practice and clinical outcomes. It will also create an innovative, robust platform and database for future research. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01655706 . Registered July 27, 2012.

Mind wandering away from pain dynamically engages antinociceptive and default mode brain networks.

Human minds often wander away from their immediate sensory environment. It remains unknown whether such mind wandering is unsystematic or whether it lawfully relates to an individual's tendency to attend to salient stimuli such as pain and their associated brain structure/function. Studies of pain-cognition interactions typically examine explicit manipulation of attention rather than spontaneous mind wandering. Here we sought to better represent natural fluctuations in pain in daily life, so we assessed behavioral and neural aspects of spontaneous disengagement of attention from pain. We found that an individual's tendency to attend to pain related to the disruptive effect of pain on his or her cognitive task performance. Next, we linked behavioral findings to neural networks with strikingly convergent evidence from functional magnetic resonance imaging during pain coupled with thought probes of mind wandering, dynamic resting state activity fluctuations, and diffusion MRI. We found that (i) pain-induced default mode network (DMN) deactivations were attenuated during mind wandering away from pain; (ii) functional connectivity fluctuations between the DMN and periaqueductal gray (PAG) dynamically tracked spontaneous attention away from pain; and (iii) across individuals, stronger PAG-DMN structural connectivity and more dynamic resting state PAG-DMN functional connectivity were associated with the tendency to mind wander away from pain. These data demonstrate that individual tendencies to mind wander away from pain, in the absence of explicit manipulation, are subserved by functional and structural connectivity within and between default mode and antinociceptive descending modulation networks.

Neural emotion regulation circuitry underlying anxiolytic effects of perceived control over pain.

Anxiolytic effects of perceived control have been observed across species. In humans, neuroimaging studies have suggested that perceived control and cognitive reappraisal reduce negative affect through similar mechanisms. An important limitation of extant neuroimaging studies of perceived control in terms of directly testing this hypothesis, however, is the use of within-subject designs, which confound participants' affective response to controllable and uncontrollable stress. To compare neural and affective responses when participants were exposed to either uncontrollable or controllable stress, two groups of participants received an identical series of stressors (thermal pain stimuli). One group ("controllable") was led to believe they had behavioral control over the pain stimuli, whereas another ("uncontrollable") believed they had no control. Controllable pain was associated with decreased state anxiety, decreased activation in amygdala, and increased activation in nucleus accumbens. In participants who perceived control over the pain, reduced state anxiety was associated with increased functional connectivity between each of these regions and ventral lateral/ventral medial pFC. The location of pFC findings is consistent with regions found to be critical for the anxiolytic effects of perceived control in rodents. Furthermore, interactions observed between pFC and both amygdala and nucleus accumbens are remarkably similar to neural mechanisms of emotion regulation through reappraisal in humans. These results suggest that perceived control reduces negative affect through a general mechanism involved in the cognitive regulation of emotion.

The Sensitivity to Pain Traumatization Scale-Child Version (SPTS-C): Development and preliminary validation.

Background: Sensitivity to pain traumatization is defined as the propensity to develop cognitive, affective, and behavioral responses to pain that resemble a traumatic stress reaction. To date, sensitivity to pain traumatization has been assessed in adults (Sensitivity to Pain Traumatization Scale [SPTS-12]) and parents of youth with chronic pain (Sensitivity to Pain Traumatization Scale-Parent version [SPTS-P]). SPT may be relevant in the context of pediatric chronic pain given the substantial comorbidity between posttraumatic stress symptoms and pain. Aims: This prospective study aimed to adapt the SPTS-12 for use in youth and to evaluate the psychometric properties of the new scale. Methods: Participants included 175 youth with chronic pain (Mage = 14.31 years, 73% girls) referred to outpatient chronic pain programs. At baseline, youth self-reported the levels of their sensitivity to pain traumatization (Sensitivity to Pain Traumatization Scale-Child version [SPTS-C]), as well as their pain symptoms, pain-related anxiety, posttraumatic stress symptoms, and attentional control. Three months later, youth self-reported their pain symptoms and completed the SPTS-C. Results: The SPTS-C had a one-factor structure that explained 48% of variance and demonstrated good reliability and construct validity. SPTS-C baseline scores predicted follow-up levels of pain interference but not pain intensity or pain unpleasantness. Conclusions: The results provide preliminary evidence for the psychometric properties of the SPTS-C and the potential role of SPT in pediatric chronic pain outcomes.

Contexte: La sensibilité à la traumatisation de la douleur est définie comme la propension à développer des réponses cognitives, affectives et comportementales à la douleur qui ressemblent à une réaction de stress traumatique. À ce jour, la sensibilité à la traumatisation de la douleur a été évaluée chez les adultes (Échelle de sensibilité à la traumatisation de la douleur [SPTS-12]) et chez les parents de jeunes souffrant de douleur chronique (Échelle de sensibilité à la traumatisation de la douleur - Version parent [SPTS-P]). La sensibilité à la traumatisation de la douleur peut être pertinente dans le contexte de la douleur chronique pédiatrique étant donné la comorbidité importante entre les symptômes de stress post-traumatique et la douleur.Objectifs: Cette étude prospective visait à adapter le SPTS-12 pour une utilisation chez les jeunes et à évaluer les propriétés psychométriques de la nouvelle échelle.Méthodes: Les participants comprenaient 175 jeunes souffrant de douleur chronique (âge M = 14,31 ans, 73 % de filles) référés aux programmes de traitement ambulatoire de la douleur chronique. Au départ, les jeunes ont autodéclaré les niveaux de leur sensibilité à la traumatisation de la douleur (Échelle de sensibilité à la traumatisation de la douleur - version enfant [SPTS-C]), ainsi que leurs symptômes de douleur, leur anxiété liée à la douleur, leurs symptômes de stress post-traumatique et leur contrôle attentionnel. Trois mois plus tard, les jeunes ont autodéclaré leurs symptômes de douleur et ont répondu au SPTS-C.Résultats: Le SPTS-C avait une structure à un facteur qui expliquait 48 % de la variance et démontrait une bonne fiabilité ainsi qu'une bonne validité de la construction. Les scores obtenus au SPTS-C au départ prédisaient les niveaux d'interférence de la douleur au suivi mais pas l'intensité de la douleur ou le désagrément de la douleur.Conclusions: Les résultats présentent des preuves préliminaires des propriétés psychométriques du SPTSC et le rôle potentiel de la sensibilité à la traumatisation de la douleur dans les résultats liés à la douleur chronique pédiatrique.

Changes in pain following bilateral intermittent theta-burst, transcranial magnetic stimulation for depression: A retrospective chart review.

Introduction: Pain management in patients with chronic pain and comorbid depression is challenging and understudied. There is interest in intermittent theta-burst stimulation (iTBS), a new modality of repetitive transcranial magnetic stimulation (rTMS). This retrospective review describes changes in pain, anxiety and depression throughout iTBS treatment at the dorsolateral prefrontal cortex (DLPFC). Methods: A retrospective chart review was conducted of patients who underwent their first acute series of iTBS treatments at the DLPFC for depression at a single institution between 2020 and 2023. Data on depression, anxiety, and pain were collected throughout iTBS treatment using the Beck Depression Inventory-II (BDI-II; higher scores indicate worse depression) and visual analogue scale (VAS; 0-100, higher scores indicate worse pain, anxiety, and depression). Nonparametric tests were used for all analyses. Results: Of 104 patients, 52 reported moderate pain at baseline (50.0%). Median BDI-II scores decreased from 38.0 (interquartile range [IQR] = 29.0-44.0) to 24.0 (IQR = 9.0-36.0) from pre- to posttreatment (P < 0.001). Of the 32 patients with both pre- and posttreatment pain scores, there was a significant decrease from 40.0 (IQR = 5.5-71.8) to 15.0 (IQR = 3.5-53.8; P = 0.037). In patients with at least moderate pain at baseline, pain scores decreased from 71.0 (IQR = 55.0-80.0) to 20.0 (IQR = 11.0-71.0; P = 0.004). Ten of 32 patients with available pre- and posttreatment scores reported ≥30% reduction in pain scores (31.2%). Conclusion: These preliminary results, suggesting decreases in pain following iTBS treatment, provide a rationale for future rigorous investigations to evaluate this intervention for depression and comorbid chronic pain.

Introduction: La prise en charge de la douleur chez les patients souffrant de douleur chronique et de dépression comorbide est difficile et sous-étudiée. Il existe un intérêt pour la stimulation thêta-burst intermittente (STBi), une nouvelle modalité de stimulation magnétique transcrânienne répétitive (SMTr). Cette revue rétrospective décrit les changements dans la douleur, l'anxiété et la dépression tout au long du traitement par STBi au niveau de la région du cortex préfrontal dorsolatéral.Un examen rétrospectif des dossiers a été mené pour les patients ayant reçu leur première série intensive de traitements par STBi pour la dépression dans la région du cortex préfrontal dorsolatéral dans un seul établissement entre 2020 et 2023. Les données sur la dépression, l'anxiété et la douleur ont été collectées tout au long des traitements par STBi à l'aide de l'Inventaire de dépression de Beck-II (IDB-II; des scores plus élevés indiquent une dépression plus grave) et de l'échelle visuelle analogique (EVA; 0-100, des scores plus élevés indiquent une aggravation de la douleur, de l'anxiété et de la dépression). Des tests non paramétriques ont été utilisés pour toutes les analyses.Résultats: Parmi les 104 patients inclus dans l'étude, 52 ont déclaré une douleur modérée au départ (50,0 %). Les scores médians de l'IDB-II ont diminué de 38,0 (intervalle interquartile [IQR] = 29,0-44,0) à 24,0 (IQR = 9,0-36,0) avant et après le traitement (P < 0,001). Parmi les 32 patients pour lesquels des scores de douleur avant et après le traitement étaient disponibles, une diminution significative a été constatée, passant de 40,0 (IQR = 5,5-71,8) à 15,0 (IQR = 3,5-53,8 ; P = 0,037). Chez les patients hospitalisés avec une douleur au moins modérée au départ, les scores de douleur ont diminué de 71,0 (IQR = 55,0-80,0) à 20,0 (IQR = 11,0-71,0 ; P = 0,004). Dix des 32 patients pour lesquels des scores avant et après le traitement étaient disponibles ont rapporté une réduction ≥30 % des scores de douleur (31,2 %).Conclusion: Ces résultats préliminaires, qui indiquent une diminution de la douleur après le traitement par STBi, offrent une justification pour la réalisation de futures études rigoureuses afin d'évaluer cette intervention pour la dépression et les douleurs chroniques comorbides.

PRECISE trial (Pain RElief Combination Intervention StratEgies): protocol for the clinical trial of a pregabalin-melatonin combination for fibromyalgia.

INTRODUCTION: Fibromyalgia is associated with chronic widespread pain and disturbed sleep. Multidisciplinary, multimodal management often includes pharmacotherapy; however, current drugs used to treat fibromyalgia provide meaningful benefit to only 30-60% of treated individuals. Combining two or more different drugs is common in clinical practice with the expectation of better efficacy, tolerability or both; however, further research is needed to identify which combinations actually provide added benefit. Thus, we are planning a clinical trial to evaluate melatonin (MLT)-pregabalin (PGB) combination in participants with fibromyalgia. METHODS AND ANALYSIS: This will be a single-centre, double-blind, randomised, double-dummy, three-period, crossover trial comparing a MLT-PGB combination to each monotherapy in 54 adult participants satisfying the 2016 American College of Rheumatology criteria for fibromyalgia. Participants will receive maximally tolerated doses of MLT, PGB and MLT-PGB combination for 6 weeks. The primary outcome will be daily pain intensity (0-10); secondary outcomes will include the Fibromyalgia Impact Questionnaire, SF-36 survey, Medical Outcomes Study Sleep Scale, Beck Depression Inventory (BDI-II), adverse events and other measures. Analysis of the primary and secondary outcomes will involve a linear mixed model with sequence, period, treatment, the first-order carryover and baseline pain score as fixed effects and participant as a random effect to test whether there are any treatment differences among three treatments and to estimate the least square mean of the mean daily pain intensity for each treatment, adjusting for carryover as well as period effects (ie, stability of pain levels). ETHICS AND DISSEMINATION: This trial has been registered with the International Standard Randomised Controlled Trial Number Registry, ISRCTN #18278231, has been granted ethical approval by the Queen's University Health Sciences Research Ethics Board (Queen's HSREB Protocol #6040998) and is currently under review for a Clinical Trial Application to Health Canada Natural and Non-prescription Health Products Directorate. All participants will provide written informed consent prior to trial participation. Following trial completion, results will be disseminated in one or more biomedical journal publications and presented at one or more scientific meetings. TRIAL REGISTRATION NUMBER: This trial has been registered with the International Standard Randomised Controlled Trial Number Registry, ISRCTN18278231.

Altered anterior insula activation during anticipation and experience of painful stimuli in expert meditators.

Experientially opening oneself to pain rather than avoiding it is said to reduce the mind's tendency toward avoidance or anxiety which can further exacerbate the experience of pain. This is a central feature of mindfulness-based therapies. Little is known about the neural mechanisms of mindfulness on pain. During a meditation practice similar to mindfulness, functional magnetic resonance imaging was used in expert meditators (>10,000 h of practice) to dissociate neural activation patterns associated with pain, its anticipation, and habituation. Compared to novices, expert meditators reported equal pain intensity, but less unpleasantness. This difference was associated with enhanced activity in the dorsal anterior insula (aI), and the anterior mid-cingulate (aMCC) the so-called 'salience network', for experts during pain. This enhanced activity during pain was associated with reduced baseline activity before pain in these regions and the amygdala for experts only. The reduced baseline activation in left aI correlated with lifetime meditation experience. This pattern of low baseline activity coupled with high response in aIns and aMCC was associated with enhanced neural habituation in amygdala and pain-related regions before painful stimulation and in the pain-related regions during painful stimulation. These findings suggest that cultivating experiential openness down-regulates anticipatory representation of aversive events, and increases the recruitment of attentional resources during pain, which is associated with faster neural habituation.

Examining the roles of depression, pain catastrophizing, and self-efficacy in quality of life changes following chronic pain treatment.

Background: Adults with chronic pain have a lower quality of life (QOL) compared to the general population. Chronic pain requires specialized treatment to address the multitude of factors that contribute to an individual's pain experience, and effectively managing pain requires a biopsychosocial approach to improve patients' QOL. Aim: This study examined adults with chronic pain after a year of specialized treatment to determine the role of cognitive markers (i.e., pain catastrophizing, depression, pain self-efficacy) in predicting changes in QOL. Methods: Patients in an interdisciplinary chronic pain clinic (N = 197) completed measures of pain catastrophizing, depression, pain self-efficacy, and QOL at baseline and 1 year later. Correlations and a moderated mediation were completed to understand the relationships between the variables. Results: Higher baseline pain catastrophizing was significantly associated with increased mental QOL (b = 0.39, 95% confidence interval [CI] 0.141; 0.648) and decreased depression (b = -0.18, 95% CI -0.306; -0.052) over a year. Furthermore, the relationship between baseline pain catastrophizing and the change in depression was moderated by the change in pain self-efficacy (b = -0.10, 95% CI -0.145; -0.043) over a year. Patients with high baseline pain catastrophizing reported decreased depression after a year of treatment, which was associated with greater QOL improvements but only in patients with unchanged or improved pain self-efficacy. Conclusions: Our findings highlight the roles of cognitive and affective factors and their impact on QOL in adults with chronic pain. Understanding the psychological factors that predict increased mental QOL is clinically useful, because medical teams can optimize these positive changes in QOL through psychosocial interventions aimed at improving patients' pain self-efficacy.

Contexte: Les adultes souffrant de douleur chronique ont une qualité de vie inférieure à celle de la population en général. La douleur chronique nécessite un traitement spécialisé pour répondre à la multitude de facteurs qui contribuent à l'expérience de la douleur d'un individu. De plus, la prise en charge efficace de la douleur nécessite une approche biopsychosociale pour améliorer la qualité de vie des patients.Objectif: Cette étude a examiné des adultes souffrant de douleur chronique après un an de traitement spécialisé pour déterminer le rôle des marqueurs cognitifs (c.-à-d. la catastrophisation de la douleur, la dépression, l'efficacité personnelle face à la douleur) dans la prévision des changements dans la qualité de vie.Méthodes: Les patients d'une clinique interdisciplinaire de la douleur chronique (N = 197) ont effectué des mesures de la catastrophisation de la douleur, de la dépression, du sentiment d'efficacité personnelle face à la douleur, ainsi que de la qualité de vie au départ et un an plus tard. Des corrélations et une médiation modérée ont été effectuées pour comprendre les relations entre les variables.Résultats: Une plus grande catastrophisation de la douleur au départ était significativement associée à une augmentation de la qualité de vie mentale (b = 0,39, intervalle de confiance à 95 % [IC] 0,141; 0,648) et à une diminution de la dépression (b = -0,18, IC à 95 % −0,306; −0,052) sur une année. En outre, la relation entre la catastrophisation de la douleur au départ et les changements en matière de dépression a été modérée par le changement dans le sentiment d'efficacité personnelle face à la douleur (b = − 0,10, IC à 95 % − 0,145; − 0,043) sur une année. Les patients démontrant une catastrophisation de la douleur élevée ont signalé une diminution de la dépression après un an de traitement, associée à de plus grandes améliorations dans la qualité de vie mais seulement chez les patients présentant un sentiment d'efficacité personnelle face à la douleur inchangée ou améliorée.Conclusions: Nos résultats mettent en évidence le rôle des facteurs cognitifs et affectifs et leur effet sur la qualité de vie chez les adultes souffrant de douleur chronique. Il est cliniquement utile de comprendre les facteurs psychologiques qui prédisent une augmentation la qualité de vie mentale, car les équipes médicales peuvent optimiser ces changements positifs dans la qualité de vie par des interventions psychosociales visant à améliorer le sentiment d'efficacité personnelle des patients face à la douleur.

Experience-based design: Empowering individuals while they wait for interprofessional chronic pain care.

OBJECTIVES: Chronic pain is highly prevalent and a leading cause of disability. Long wait times for interprofessional care provide an opportunity to introduce web-based interventions that improve psychosocial function and patients' readiness and ability to manage their condition. Here we describe the process of partnering with people with lived experience (PWLE) to develop an online self-management program enhanced by motivational interviewing. We also report the multiphase usability testing of the program. METHODS: PWLE were included in all aspects of this project from program inception to content creation, module development, usability testing, and knowledge dissemination. Phase 1 included the development of the interactive, web-based modules. This process involved weekly meetings and asynchronous content creation with a core team of interprofessional pain experts, researchers, and PWLE. Phase 2 included usability testing by our PWLE and clinical expert advisory. Phase 3 included survey-based usability testing with a sample of 10 PWLE. RESULTS: We created a chronic pain & motivational empowerment program includes a series of eight interactive educational web-based modules. Topics included: setting expectations, chronic pain explained, biopsychosocial factors, empowered management, self-awareness & compassion & acceptance, values, goal setting, and communication. The program is accompanied by a reflection journal and can be enhanced by one-on-one coaching sessions using a motivational interviewing approach. Phase two usability testing resulted in numerous content changes and the addition of accessibility features. Phase 3 usability testing with PWLE found the program highly accessible and easy to use. CONCLUSIONS: The engagement of our PWLE team member and advisors made the online program more relevant, sensitive and helpful to the needs of people with pain. PRACTICAL VALUE: This PWLE-centric project sets the foundation for future work to examine the feasibility and effectiveness of the program for supporting individuals with chronic pain self-manage.

Investigating the relationship between pain indicators and observers' judgements of pain.

BACKGROUND: Due to the inherent subjectivity of pain, it is difficult to make accurate judgements of pain in others. Research has found discrepancies between the ways in which perceived "objective" (e.g., medical evidence of injury) and "subjective" information (e.g., self-report) influence judgements of pain. This study aims to explore which potential cues (depictions of sensory input, brain activation, self-reported pain and facial expressions) participants are most influenced by when evaluating pain in others. METHODS: First, 60 participants (23 women, 36 ± 10 years old) judged who was in more pain between two different pain indicators representing two different patients. These trials revealed which congruent indicator (i.e., two high pain indicators) would most influence participant decisions. Second, participants prescribed quantities of analgesia for one patient's pain based on two different pain indicators. These trials revealed which incongruent indicators (i.e., one high and one low indicator) would most influence participant decisions. RESULTS: As predicted, facial expressions were perceived as subjective and were the least likely, among all pain indicators, to influence observer's judgements of pain. Participants relied upon indicators they perceived as objective. Self-report pain ratings had the greatest influence on participants judgements about how much analgesic cream to prescribe and was perceived as objective by half of the participants. CONCLUSIONS: We found that in situations where incongruent information was presented about an individual's pain, participants relied on pain indicators that they perceived to be objective. The current study provides important insights about biases that people hold when making judgements of pain in others. SIGNIFICANCE: Interpretation and assessment of pain remains one of the largest barriers to pain management and involves complex, idiosyncratic processing. This study provides insights into what information participants view as critical in making attributions of pain when presented with multiple, seemingly incongruent sources of information.

Do "central sensitization" questionnaires reflect measures of nociceptive sensitization or psychological constructs? A systematic review and meta-analyses.

ABSTRACT: Central sensitization (CS) is defined as an increased nociceptive responsiveness due to sensitization of neurons in the central nervous system, usually the result of prolonged nociceptive input or a disease state associated with noxious inputs (eg, polyarthritis). The concept of CS has recently been adopted in clinical assessments of chronic pain, but its diagnosis in humans may now include a wide range of hypervigilant responses. The purpose of this review is to ascertain whether self-report questionnaires linked with CS are associated with enhanced nociceptive responses or whether they measure sensitivity in a broader sense (ie, emotional responses). According to our published, PROSPERO-registered review protocol (CRD42021208731), a predefined search of studies that involve the Central Sensitization Inventory (CSI) or Pain Sensitivity Questionnaire (PSQ), correlated with either nociceptive sensory tests or emotional hypervigilance was conducted on MEDLINE, PsycINFO, and Web of Science. Correlations between the CSI or PSQ with our primary outcomes were extracted and meta-analysed. A review of 66 studies totalling 13,284 participants found that the CSI (but not the PSQ) strongly correlated with psychological constructs: depression, anxiety, stress, pain catastrophising, sleep, and kinesiophobia. The CSI and PSQ showed weak or no correlations with experimental measures of nociceptive sensitivity: pain thresholds, temporal summation, or conditioned pain modulation. The PSQ did, however, correlate strongly with phasic heat and tonic cold pain tests. The studies reviewed did not provide sufficient evidence that self-report measures reflect a canonical understanding of CS. The CSI more closely reflects psychological hypervigilance than increased responsiveness of nociceptive neurons.

Patient Expectations and Therapeutic Alliance Affect Pain Reduction Following Lidocaine Infusion in an Interdisciplinary Chronic Pain Clinic.

Pain experience is affected by both ascending nociceptive signals and descending modulation. Expectations can affect pain experience and augment treatment-induced analgesia through descending inhibitory modulation of pain. This open-label, prospective cohort study examined the association between participant expectation ratings and pain reduction in adult participants with chronic pain receiving an intravenous lidocaine infusion. We aimed to explore whether: 1) participants' expectations of treatment efficacy were associated with pain reduction over 8 weeks after infusion; and 2) participants' therapeutic alliance was associated with expectations and/or pain reduction. We recruited 70 participants with chronic pain scheduled for lidocaine infusion. Study measures included pain intensity (pre-treatment, post-treatment, and daily for 8 weeks), treatment expectations (EXPECT), and therapeutic alliance (Trust in Physician and Working Alliance Inventory-Short Revised). Baseline treatment expectations were significantly correlated with pain reduction (r = .42, P < .01). Therapeutic alliance was significantly correlated with expectations (r = .27, P < .05) and pain reduction (r = .38, P < .01). This study quantifies the contribution of: 1) treatment expectations; and 2) therapeutic alliance to the magnitude of lidocaine-induced pain reduction. Results generate the hypothesis that focused efforts to augment treatment expectations and therapeutic alliance could serve to improve pain treatment outcomes. PERSPECTIVE: This study evaluates the relationship between pain reduction and ratings of: 1) treatment expectations; and 2) therapeutic alliance following an intravenous lidocaine infusion. Results generate the hypothesis that focused efforts to augment treatment expectations and therapeutic alliance could serve to improve pain treatment outcomes.

Resting-state neural mechanisms of capability for suicide and their interaction with pain - A CAN-BIND-05 Study.

BACKGROUND: Suicidal ideation is highly prevalent in Major Depressive Disorder (MDD). However, the factors determining who will transition from ideation to attempt are not established. Emerging research points to suicide capability (SC), which reflects fearlessness of death and increased pain tolerance, as a construct mediating this transition. This Canadian Biomarker Integration Network in Depression study (CANBIND-5) aimed to identify the neural basis of SC and its interaction with pain as a marker of suicide attempt. METHODS: MDD patients (n = 20) with suicide risk and healthy controls (n = 21) completed a self-report SC scale and a cold pressor task measuring pain threshold, tolerance, endurance, and intensity at threshold and tolerance. All participants underwent a resting-state brain scan and functional connectivity was examined for 4 regions: anterior insula (aIC), posterior insula (pIC), anterior mid-cingulate cortex (aMCC) and subgenual anterior cingulate cortex (sgACC). RESULTS: In MDD, SC correlated positively with pain endurance and negatively with threshold intensity. Furthermore, SC correlated with the connectivity of aIC to the supramarginal gyrus, pIC to the paracingulate gyrus, aMCC to the paracingulate gyrus, and sgACC to the dorsolateral prefrontal cortex. These correlations were stronger in MDD compared to controls. Only threshold intensity mediated the correlation between SC and connectivity strength. LIMITATIONS: Resting-state scans provided an indirect assessment of SC and the pain network. CONCLUSIONS: These findings highlight point to a neural network underlying SC that is associated with pain processing. This supports the potential clinical utility of pain response measurement as a method to investigate markers of suicide risk.

Amygdalar function reflects common individual differences in emotion and pain regulation success.

Although the co-occurrence of negative affect and pain is well recognized, the mechanism underlying their association is unclear. To examine whether a common self-regulatory ability impacts the experience of both emotion and pain, we integrated neuroimaging, behavioral, and physiological measures obtained from three assessments separated by substantial temporal intervals. Our results demonstrated that individual differences in emotion regulation ability, as indexed by an objective measure of emotional state, corrugator electromyography, predicted self-reported success while regulating pain. In both emotion and pain paradigms, the amygdala reflected regulatory success. Notably, we found that greater emotion regulation success was associated with greater change of amygdalar activity following pain regulation. Furthermore, individual differences in degree of amygdalar change following emotion regulation were a strong predictor of pain regulation success, as well as of the degree of amygdalar engagement following pain regulation. These findings suggest that common individual differences in emotion and pain regulatory success are reflected in a neural structure known to contribute to appraisal processes.

Turning on the alarm: the neural mechanisms of the transition from innocuous to painful sensation.

The experience of pain occurs when the level of a stimulus is sufficient to elicit a marked affective response, putatively to warn the organism of potential danger and motivate appropriate behavioral responses. Understanding the biological mechanisms of the transition from innocuous to painful levels of sensation is essential to understanding pain perception as well as clinical conditions characterized by abnormal relationships between stimulation and pain response. Thus, the primary objective of this study was to characterize the neural response associated with this transition and the correspondence between that response and subjective reports of pain. Towards this goal, this study examined BOLD response profiles across a range of temperatures spanning the pain threshold. 14 healthy adults underwent functional magnetic resonance imaging (fMRI) while a range of thermal stimuli (44-49°C) were applied. BOLD responses showed a sigmoidal profile along the range of temperatures in a network of brain regions including insula and mid-cingulate, as well as a number of regions associated with motor responses including ventral lateral nuclei of the thalamus, globus pallidus and premotor cortex. A sigmoid function fit to the BOLD responses in these regions explained up to 85% of the variance in individual pain ratings, and yielded an estimate of the temperature of steepest transition from non-painful to painful heat that was nearly identical to that generated by subjective ratings. These results demonstrate a precise characterization of the relationship between objective levels of stimulation, resulting neural activation, and subjective experience of pain and provide direct evidence for a neural mechanism supporting the nonlinear transition from innocuous to painful levels along the sensory continuum.

Perceived helplessness is associated with individual differences in the central motor output system.

Learned helplessness is a maladaptive response to uncontrollable stress characterized by impaired motor escape responses, reduced motivation and learning deficits. There are important individual differences in the likelihood of becoming helpless following exposure to uncontrollable stress but little is known about the neural mechanisms underlying these individual differences. Here we used structural MRI to measure gray and white matter in individuals with chronic pain, a population at high risk for helplessness due to prolonged exposure to a poorly controlled stressor (pain). Given that self-reported helplessness is predictive of treatment outcomes in chronic pain, understanding such differences might provide valuable clinical insight. We found that the magnitude of self-reported helplessness correlated with cortical thickness in the supplementary motor area (SMA) and midcingulate cortex, regions implicated in cognitive aspects of motor behavior. We then examined the white matter connectivity of these regions and found that fractional anisotropy of connected white matter tracts along the corticospinal tract was associated with helplessness and mediated the relationship between SMA cortical thickness and helplessness. These data provide novel evidence that links individual differences in the motor output pathway with perceived helplessness over a chronic and poorly controlled stressor.