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.

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.

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.

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.

Using electronically delivered therapy and brain imaging to understand OCD pathology: A pilot feasibility study.

Background: Obsessive-compulsive disorder (OCD) is a debilitating mental health disorder with current psychotherapeutic treatments, while somewhat effective, yielding low accessibility and scalability. A lack of knowledge regarding the neural pathology of OCD may be hindering the development of innovative treatments. Previous research has observed baseline brain activation patterns in OCD patients, elucidating some understanding of the implications. However, by using neuroimaging to observe the effects of treatment on brain activation, a more complete picture of OCD can be drawn. Currently, the gold standard treatment is cognitive behavioral therapy (CBT). However, CBT is often inaccessible, time-consuming, and costly. Fortunately, it can be effectively delivered electronically (e-CBT). Objectives: This pilot study implemented an e-CBT program for OCD and observed its effects on cortical activation levels during a symptom provocation task. It was hypothesized that abnormal activations could be attenuated following treatment. Methods: OCD patients completed a 16-week e-CBT program administered through an online platform, mirroring in-person content. Treatment efficacy was evaluated using behavioral questionnaires and neuroimaging. Activation levels were assessed at the resting state and during the symptom provocation task. Results: In this pilot, seven participants completed the program, with significant improvements (p < 0.05) observed between baseline and post-treatment for symptom severity and levels of functioning. No statistically significant (p = 0.07) improvement was observed in the quality of life. Participants had mostly positive qualitative feedback, citing accessibility benefits, comprehensive formatting, and relatable content. No significant changes in cortical activation were observed between baseline and post-treatment. Conclusion: This project sheds light on the application of e-CBT as a tool to evaluate the effects of treatment on cortical activation, setting the stage for a larger-scale study. The program showed great promise in feasibility and effectiveness. While there were no significant findings regarding changes in cortical activation, the trends were in agreeance with previous literature, suggesting future work could provide insight into whether e-CBT offers comparable cortical effects to in-person psychotherapy. Applying a greater knowledge of the neural mechanisms of action in OCD can help develop novel treatment plans in the future.

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.

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.

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.

Is Pain "All in your Mind"? Examining the General Public's Views of Pain.

By definition, pain is a sensory and emotional experience that is felt in a particular part of the body. The precise relationship between somatic events at the site where pain is experienced, and central processing giving rise to the mental experience of pain remains the subject of debate, but there is little disagreement in scholarly circles that both aspects of pain are critical to its experience. Recent experimental work, however, suggests a public view that is at odds with this conceptualisation. By demonstrating that the public does not necessarily endorse central tenets of the "mental" view of pain (subjectivity, privacy, and incorrigibility), experimental philosophers have argued that the public holds a more "body-centric" view than most clinicians and scholars. Such a discrepancy would have important implications for how the public interacts with pain science and clinical care. In response, we tested the hypothesis that the public is capable of a more "mind-centric" view of pain. Using a series of vignettes, we demonstrate that in situations which highlight mental aspects of pain the public can, and does, recognize pain as a mental phenomenon. We also demonstrate that the public view is subject to context effects, by showing that the public's view is modified when situations emphasizing mental and somatic aspects of pain are presented together.

Conditioned pain modulation is associated with heightened connectivity between the periaqueductal grey and cortical regions.

Introduction: Conditioned pain modulation (CPM) is a psychophysical assessment used to estimate the efficiency of an individual's endogenous modulatory mechanisms. Conditioned pain modulation has been used as a predictive assessment for the development of chronic pain and responses to pain interventions. Although much is known about the spinal cord mechanisms associated with descending pain modulation, less is known about the contribution of supraspinal and especially cortical regions. Objectives: We aimed to explore how whole-brain connectivity of a core modulatory region, the periaqueductal grey (PAG), is associated with conditioned pain modulation, and endogenous pain modulation more broadly. Methods: We measured CPM and resting-state connectivity of 35 healthy volunteers, absent of chronic pain diagnoses. As a region of interest, we targeted the PAG, which is directly involved in endogenous modulation of input to the spinal cord and is a key node within the descending pain modulation network. Results: We found that CPM was associated with heightened connectivity between the PAG and key regions associated with pain processing and inhibition, such as the primary and secondary somatosensory cortices, as well as the motor, premotor, and dorsolateral prefrontal cortices. These findings are consistent with connectivity findings in other resting-state and event-related fMRI studies. Conclusion: These findings indicate that individuals who are efficient modulators have greater functional connectivity between the PAG and regions involved in processing pain. The heightened connectivity of these regions may contribute to the beneficial outcomes in clinical pain management, as quantified by CPM. These results may function as brain-based biomarkers for vulnerability or resilience to pain.

Pain severity and pain interference during major depressive episodes treated with escitalopram and aripiprazole adjunctive therapy: a CAN-BIND-1 report.

Escitalopram may have pain-alleviating effects for patients with comorbid pain and depression. This study aimed to quantify improvements in pain for patients on escitalopram and adjunctive aripiprazole. A secondary analysis of the CAN-BIND-1 trial was conducted which only included participants with a current depressive episode and pain. Participants received escitalopram (10-20mg) for eight weeks and treatment response was defined as a reduction in Montgomery-Åsberg Depression Rating Scale (MADRS) of at least 50% from baseline. Non-responders at week 8 received adjunctive aripiprazole (2-10mg) for another eight weeks. The Brief Pain Inventory's pain severity (PSC) and pain interference (PIC) composite scores were measured at baseline, week 8, and week 16. Linear regression was used to determine how PSC and PIC differed between treatment responders and non-responders. Eighty-two participants with pain and depression received escitalopram. PSC and PIC decreased significantly regardless of treatment response at week 8, although responders had significantly lower PSC and PIC than non-responders. For the group receiving aripiprazole after week 8, neither PSC nor PIC improved further. Further research is needed to identify interventions that might treat both pain and depression symptoms.

Sensitivity to Pain Traumatization and Its Relationship to the Anxiety-Pain Connection in Youth with Chronic Pain: Implications for Treatment.

The bidirectional relationship between anxiety and chronic pain in youth is well-known, but how anxiety contributes to the maintenance of pediatric chronic pain needs to be elucidated. Sensitivity to pain traumatization (SPT), an individual's propensity to develop responses to pain that resemble a traumatic stress response, may contribute to the mutual maintenance of anxiety and pediatric chronic pain. A clinical sample of youth (aged 10-18 years) with chronic pain completed a measure of SPT at baseline and rated their anxiety and pain characteristics for seven consecutive days at baseline and at three-month follow-up. Multiple linear regression analyses were conducted to model whether SPT moderated the relationship between baseline anxiety and pain intensity, unpleasantness, and interference three months later. SPT significantly moderated the relationship between anxiety and pain intensity. High anxiety youth with high SPT reported increased pain intensity three months later, while high anxiety youth with low SPT did not. High anxiety youth who experience pain as potentially traumatizing are more likely to report higher pain intensity three months later than high-anxiety youth who do not. Future research should examine whether children's propensity to become traumatized by their pain predicts the development of chronic pain and response to intervention.

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 chronic disease helplessness survey: developing and validating a better measure of helplessness for chronic conditions.

Introduction: Learned helplessness develops with prolonged exposure to uncontrollable stressors and is therefore germane to individuals living with pain or other poorly controlled chronic diseases. This study has developed a helplessness scale for chronic conditions distinct from previous scales that blur the conceptualization of control constructs. Extant measures commonly examine controllability, not the three pillars of helplessness identified by Maier and Seligman (1976): cognitive, emotional, and motivational/motor deficits. Methods: Individuals who self-report a chronic pain condition (N = 350) responded to a Chronic Disease Helplessness Survey (CDHS) constructed to capture cognitive, motivational/motor, and emotion deficits. Exploratory factor analysis (EFA; N = 200) and confirmatory factor analysis (CFA; N = 150) were performed. The CDHS was assessed for convergent and discriminant validity. Results: A three-factor solution corresponding to cognitive, emotional, and motivational/motor factors was identified by EFA. The solution exhibited sufficient model fit and each factor had a high degree of internal consistency. The CDHS was significantly associated with greater pain intensity and interference, PCS helplessness, lower perceived pain control, and lower general self-efficacy. Individuals with diabetes generally experience greater control strategies over daily symptoms (e.g., diet, oral medications, and insulin) than patients with chronic pain and in this study displayed significantly lower CDHS scores compared to individuals with chronic pain, demonstrating discriminant validity. Conclusions: This study provides preliminary evidence that the three-factor CDHS is a psychometrically sound measure of helplessness in individuals with chronic pain.

Pain priors, polyeidism, and predictive power: a preliminary investigation into individual differences in ordinary thought about pain.

According to standard philosophical and clinical understandings, pain is an essentially mental phenomenon (typically, a kind of conscious experience). In a challenge to this standard conception, a recent burst of empirical work in experimental philosophy, such as that by Justin Sytsma and Kevin Reuter, purports to show that people ordinarily conceive of pain as an essentially bodily phenomenon-specifically, a quality of bodily disturbance. In response to this bodily view, other recent experimental studies have provided evidence that the ordinary ('folk') concept of pain is more complex than previously assumed: rather than tracking only bodily or only mental aspects of pain, the ordinary concept of pain can actually track either of these aspects. The polyeidic (or 'many ideas') analysis of the folk concept of pain, as proposed by Emma Borg et al., captures this complexity. Whereas previous empirical support for the polyeidic view has focused on the context-sensitivity of the folk concept of pain, here we discuss individual differences in people's 'pain priors'-namely, their standing tendencies to think of pain in relatively mind-centric or body-centric ways. We describe a preliminary empirical study and present a small number of findings, which will be explored further in future work. The results we discuss are part of a larger programme of work which seeks to integrate philosophical pain research into clinical practice. For example, we hypothesise that variations in how patients with chronic pain are thinking about pain could help predict their responses to treatment.

Do "central sensitization" questionnaires reflect measures of nociceptive sensitization or psychological constructs? Protocol for a systematic review.

INTRODUCTION: Central sensitization (CS) was first defined in animal studies to be increased nociceptive responsiveness due to sensitization of neurons in the central nervous system, usually the result of prolonged nociceptive input or a disease state. Recently, the concept of CS has been adopted in clinical assessments of chronic pain, but its diagnosis in humans has expanded to include the enhancement of a wide range of nociceptive, sensory, and emotional responses. Many poorly understood pain disorders are referred to as "central sensitivity syndrome," a term associated with a broad range of hypervigilant sensory and emotional responses. Diagnosis often involves a review of medical records and an assessment of behaviour, emotional disposition, and overall sensitivity of a patient. Obviously, these assessments are unable to directly capture the responsiveness of nociceptive neurons. The purpose of this review is to ascertain whether self-report questionnaires associated with central sensitization and the diagnosis of central sensitivity syndrome are associated with enhanced nociceptive responses or whether they more validly measure sensitivity in a broader sense (ie, including emotional responses). METHODS: Following the PRISMA guidelines, a detailed search of studies that involve the Central Sensitization Inventory or Pain Sensitivity Questionnaire correlated with either nociceptive sensory tests (quantitative sensory testing) or emotional hypervigilance (anxiety, depression, stress, etc) will be conducted on MEDLINE, PsychINFO, and Web of Science. PERSPECTIVE: The review is expected to synthesize correlations between sensitivity questionnaires and nociceptive or emotional sensitivity to determine whether these questionnaires reflect a broadened understanding of the term "central sensitization."