The Brief Pain Inventory (BPI) pain interference subscale has been used as a measure of pain-related disability, a core outcome domain in the pain field. However, the pain interference subscale captures a broad range of experiences, and some items overlap with measures of distinct constructs. This overlap may inflate estimates in predictive studies and limits the precision with which treatment effects can be evaluated. To prompt reflection on appropriate use of the BPI pain interference items, this study investigated their relevance for assessing 'pain-related disability'. Participants with and without chronic pain (final sample, n=94) were presented with definitions of 'pain-related disability' and other relevant constructs, including 'pain severity', 'pain-related distress', 'depression', 'anxiety', and 'sleep disturbance'. Participants rated the degree to which items from widely used questionnaires captured the respective constructs. Linear mixed effects models examined the extent to which BPI pain interference items were rated as capturing 'pain-related disability' versus other constructs. Results indicated that the pain interference items, when considered altogether, appear to be distinct from the constructs of 'depression', 'anxiety', and 'sleep disturbance', but not from 'pain severity' and 'pain-related distress'. However, no individual item was judged to only measure 'pain-related disability' and some were judged to reflect other constructs. Although replication in a larger sample of people with pain is needed, the pain interference items capture multifaceted aspects of several constructs. Optimal use of the items requires reflection of whether they are 'fit for purpose' for the intended construct and context for which they are used. PERSPECTIVE: The Brief Pain Inventory (BPI) pain interference subscale has been used as a measure of 'pain-related disability'. BPI pain interference items do not only measure 'pain-related disability'. Appropriate use of the items requires reflection of whether they are 'fit for purpose' for the intended construct and context.

Past research has demonstrated that pain experience can be manipulated through non-specific effects. Placebo analgesia (PA) is known to be sensitive to an individual's expectations of pain relief. This study aimed to investigate the relationship between the spinal cord, midbrain, and cortical regions commonly associated with expectancy-induced PA. Fifty healthy participants underwent separate brain and spinal fMRI scans involving application of painful heat in four conditions: baseline, placebo analgesia (PA), placebo match (PM; i.e., stimulus adjusted to match PA pain intensity), and repeated baseline (RB). PA was induced through a verbal expectation manipulation with an inert cream. Pain-related functional connectivity (FC) between the dorsolateral prefrontal cortex and periaqueductal gray (PAG), as well as right dorsal C6 and PAG, was calculated. Pain-related functional activation in right dorsal C6 and PAG was also characterized. Results demonstrated a significant placebo analgesic response with decreased pain intensity from baseline to PA conditions. Spinal cord FC revealed greater activation in the periaqueductal gray (PAG) and right dorsal C6 during PA compared to baseline. PAG-C6 FC was significant in all conditions except baseline and was positively associated with pain intensity and expected pain in the PA condition. Double mediation analysis indicated an indirect effect of expected pain on pain intensity through PAG-C6 FC in the PA condition. These findings highlight the critical role of the midbrain-spinal cord pathway in translating expectancy-based placebo into a reduction of perceived pain intensity and underscore the importance of considering cortico-midbrain-spinal mechanisms in understanding placebo analgesia. PERSPECTIVE: Prior neuroimaging studies suggest placebo-related pain reduction is an active pain modulatory process. However, these studies typically do not integrate both spinal and brain fMRI within the same cohort. Combining modalities, our results suggest an important role for midbrain-spinal connectivity as a mediator of expectancy-based placebo analgesia.

As of 2022, an estimated 18 million individuals in the United States were living as cancer survivors, a number projected to rise to approximately 26 million by 2040. Advances in treatment and early detection have improved the 5-year cancer survival rate from 35% in 1960 to 65% today. However, cancer treatment often takes its own toll, and multi-modal treatments can have life-long consequences themselves, particularly in the form of chronic pain, which is known to compound the physical and emotional burden of cancer. In this review, we examine the complex burden of cancer-related pain, using breast cancer as a representative case. We first outline current pain management strategies, then highlight emerging non-pharmacological approaches that show promise in enhancing treatment outcomes. Among these, placebo effects and specifically, the role of the patient's expectations, represent compelling and safe avenues for non-pharmacological modes of symptom relief. Critically, we position expectation modulation not as a substitute but as an adjuvant to pharmacological interventions, targeting the psychosocial dimensions of pain without adding to the side-effect burden. Finally, we explore virtual reality and other extended reality technologies as innovative tools for delivering expectation-based interventions, offering scalable, immersive, and engaging platforms for integrated management of pain and other symptoms.

Chronic pain alters resting-state cerebral alpha rhythms (8-12 Hz), including whole-brain slowing of peak alpha frequency (PAF). Nevertheless, how the power of brain activity at PAF (PAF power) or across the entire alpha frequency range (alpha power) is decreased or increased compared to healthy controls (HC) varies greatly across pain phenotypes. The brain regions exhibiting such alterations and their association with the pain severity experienced by patients are also unclear. The study addressed this question in participants experiencing complex regional pain syndrome (CRPS; 19 females and 10 males) against pain-free HC (14 females and 15 males). Resting-state magnetoencephalography imaging was used to estimate the power spectral density of neurophysiological activity across the cortex to identify group differences in alpha activity. The study found decreased alpha power and slower PAF in patients with CRPS, especially over bilateral posteromedial regions including the precuneus, paracentral and superior parietal cortices. In CRPS, pain severity was associated with the suppression of PAF power in the medial and lateral prefrontal cortex (PFC) and orbitofrontal cortex (OFC). Furthermore, the same PFC and OFC areas showed increased interregional alpha-band functional connectivity in patients with CRPS. Although the greatest pain-related alpha alterations mapped to sensory-discriminative areas, including the posteromedial cortex, PFC alpha activity encoded subjective CRPS pain severity. Hyperconnectivity between medial PFC and OFC further emphasized the affective-motivational nature of CRPS pain. Overall, these findings highlight the multiple functional roles of alpha activity in nociplastic conditions such as CRPS and provide potential targets for neuromodulatory interventions. PERSPECTIVE: Complex regional pain syndrome (CRPS) is a debilitating disorder driven by altered brain processes. The authors characterize deviations in alpha brain activity in CRPS compared to healthy controls which could inform the development of novel neuromodulation therapies.

Chronic low back pain (LBP), often correlated with intervertebral disc degeneration, is a leading source of disability worldwide, yet remains poorly understood. Current treatments often fail to provide sustained relief, highlighting the need to better understand the mechanisms driving discogenic LBP. During disc degeneration, the extracellular matrix degrades, allowing nociceptive nerve fibers to innervate previously aneural disc regions. Persistent mechanical and inflammatory stimulation of nociceptors can induce plastic changes within dorsal root ganglia (DRG) neurons, characterized by altered gene expression, enhanced excitability, and lowered activation thresholds. Although these transcriptional changes have been described in other pain states, including osteoarthritis, they remain underexplored in discogenic LBP. To address this gap, this study represents the first application of comprehensive single-nuclei RNA sequencing of T13-L1 bilateral DRG neurons in a female Sprague Dawley rat model of chronic discogenic LBP, 15 weeks post-injury. Eighteen distinct DRG subpopulations were identified and mapped to existing mouse and cross-species atlases revealing strong similarities in neuronal populations with the mouse. Differential expression analysis revealed increased expression of pain-associated genes, including Scn9a and Piezo2, and neuroinflammatory mediators such as Fstl1 and Ngfr, in LBP animals. Axial hypersensitivity, measured using grip strength, significantly correlated with increased expression of Scn9a, Fstl1, and Ngfr, which suggests their role in maintaining axial hypersensitivity in this model. These findings establish a relationship between DRG transcriptomic changes and axial hypersensitivity in a discogenic LBP model, identifying potential molecular targets for non-opioid treatments and advancing understanding of discogenic LBP mechanisms. PERSPECTIVE: This study identifies transcriptomic changes in sensory neurons linked to axial hypersensitivity in a rat model of chronic discogenic low back pain. These findings highlight potential molecular targets for non-opioid therapies and may help to better understand the neuronal mechanisms underlying persistent discogenic pain.

Preclinical models of osteoarthritis (OA) can provide insights into joint-level remodeling and pain-related behaviors, but effects beyond the joint are poorly understood. The current study investigates joint remodeling and brain remodeling using aged rats in a surgical rodent model of post-traumatic OA. Male and female Fischer 344 rats (68 weeks old) received either a skin incision (n=6 male and n=10 female) or medial collateral ligament transection plus medial meniscus transection (MCLT+MMT) surgery (n=5 male and n=11 female). Tactile sensitivity was assessed pre-surgery and 4-, 8-, 12-, and 16-weeks post-surgery. Neuroimaging was performed pre-surgery and 6- and 14-weeks post-surgery, with analyses focused on gray matter volume, blood oxygen level dependent (BOLD) signal, and functional connectivity. Following euthanasia, histological analysis was performed to assess joint changes. Histology confirmed advanced cartilage loss and bone damage in animals with MCLT+MMT animals relative to skin-incision sham; however, tactile sensitivity decreased over time for both surgery groups. From the neuroimaging data, differences between the MCLT+MMT and skin-incision groups were present for both males and females at week 6 and week 14. Differences include gray matter volume, BOLD signal, and functional connectivity in regions responsible for pain transmission and modulation (thalamus, somatosensory cortex, and periaqueductal gray), along with the emotional and affective aspects of pain (striatum, hippocampus, prefrontal cortex, and amygdala). Despite a lack of differences in tactile sensitivity between groups, these findings in the central circuits involved in sensory and nociceptive processing indicate an association with knee OA development and brain remodeling. PERSPECTIVE: This work is the first to examine brain remodeling in the acute and chronic stages of osteoarthritis pain using the medial meniscus transection model in aged animals. Results demonstrate evidence of brain remodeling in a preclinical model of osteoarthritis and help elucidate osteoarthritis effects beyond the joint.

Despite recognition that osteoarthritis (OA) pain is dynamic, most clinical trials rely on static, single-point assessments. This study examined whether daily pre-treatment pain variability predicts treatment response in OA. We retrospectively analyzed data from 345 knee OA patients enrolled in two randomized, double-blind trials comparing naproxen (500 mg BID; n=190) to placebo (n=155). Participants reported daily pain (0-10 NRS) over 117 days (5-day baseline + 112-day treatment). Pain variability before treatment was quantified using: (1) standard deviation (pre-treatment pain variability, PTPV); (2) autocorrelation (AR); and (3) probability of acute change (PAC; ≥2-point shift). Logistic regression assessed responder status (≥30% pain reduction), and linear mixed-effects models evaluated longitudinal pain changes. Participants were stratified by treatment arm and high/low PTPV (median split). Correlations between variability metrics were also analyzed. Higher PTPV significantly predicted treatment response at Weeks 4, 8, 12, and 16 (p<0.05). Though both groups improved, participants receiving naproxen with high PTPV showed significantly greater pain reduction over time (p<0.001) compared to those with low variability and placebo subgroups. PTPV was not correlated with baseline pain, indicating independence from pain severity. Variability metrics captured distinct aspects of the pain experience: PTPV and PAC were strongly correlated (r=0.67), AR was negatively correlated with PAC (r=-0.25), and weakly with PTPV (r=0.12). Importantly none was associated with mean pain levels. Our study shows pre-treatment pain variability is a robust, independent predictor of response to both active drug and placebo. We suggest incorporating dynamic pain metrics may improve outcome prediction and trial design in OA. PERSPECTIVE: This study demonstrates that pre-treatment pain variability reflects unique aspects of the pain experience, independent of average pain intensity. Its consistent association with treatment response-regardless of intervention-supports its value as a predictive marker. Incorporating variability into clinical trial design may enhance outcome sensitivity and improve patient stratification.

This study aimed to investigate the feasibility, acceptability, and effects of dry needling in women with provoked vestibulodynia. Forty-six women diagnosed with provoked vestibulodynia were randomized to receive six weekly sessions of either real or sham dry needling (DN). Participants, investigators and data analysts were blinded. Feasibility outcomes (adherence to treatment, questionnaire completion and dropout rate) and side effects were measured throughout the study. Pain intensity during intercourse (0-10 numeric rating scale) was measured at baseline and posttreatment, and acceptability (questionnaire) was assessed at posttreatment. Women in the realDN group attended 99% of the planned treatment sessions, compared to 91% in the shamDN group. Additionally, 100% of the questionnaires were completed in the realDN group, compared to 93% in the shamDN group. All participants in the realDN group completed the study. In contrast, two participants in the shamDN group withdrew. For the main side effects, 96% of the participants in the realDN group and 52% in the shamDN group experienced muscle aches (p<.001). Moreover, 35% experienced autonomic reactions in the realDN group, while these were not observed in the shamDN group (p<.001). All participants reported high levels of acceptability across all dimensions, with no significant difference between groups. The realDN group showed a significant decrease in pain intensity compared to the shamDN group (mean difference between groups 2.4; 95%CI 1.4-3.3; p<.001). Our findings support the feasibility and acceptability of dry needling to treat women with provoked vestibulodynia and showed a significant effect in reducing pain. PERSPECTIVE: This article presents the results of a novel study examining the feasibility and acceptability of using dry needling to treat women suffering from provoked vestibulodynia and lays the groundwork to inform a future randomized controlled trial.

Our research, in line with previous literature, has indicated that pain-related stigma plays a role in pain outcomes for children and adolescents with chronic musculoskeletal pain conditions. However, the influence of pain-related stigma on functioning and internalizing symptoms is less clear, as is whether stigma may differently influence youth dependent on gender and chronic pain type. The current study was a secondary analysis of cross-sectional data from 32 youth with Juvenile Idiopathic Arthritis (JIA), 31 youth with Juvenile Primary Fibromyalgia Syndrome (JFM), and 25 youth with non-specific chronic pain (NSCP) from a study examining group differences and biopsychosocial correlates of chronic musculoskeletal pain conditions. Participants self-reported their pain-related stigma, pain, physical, school, emotional and social functioning, and symptoms of anxiety and depression. Multiple regression analyses assessed associations between pain-related stigma and functioning, and pain-related stigma and internalizing symptoms, as well as interactions between stigma and gender as well as stigma and chronic pain type. Results showed that pain-related stigma significantly influenced physical and social functioning across groups. Stigma was associated with worse emotional functioning for girls, who also reported worse overall emotional functioning and greater anxiety and depression symptoms. Youth with JFM and NSCP demonstrated lower functioning compared to children and adolescents with JIA. These findings indicate that stigma substantially influences functioning and wellbeing of children and adolescents with chronic pain, especially for girls. Regardless of stigma experienced, those with chronic pain diagnoses lacking a known pathophysiology reported lower functioning in several domains. PERSPECTIVE: Youth with chronic musculoskeletal pain experience stigma about their pain which contributes not only to pain outcomes, but also physical and social functioning. Girls and youth with chronic pain conditions with unclear pathophysiology are especially at risk for adverse outcomes.

Patients with schwannomatosis (SWN) develop multiple tumors, called schwannomas, along peripheral nerves, with most experiencing significant pain. Neuropathic, nociceptive, and inflammatory pain types have been reported, but many patients describe severe pain when a schwannoma is palpated or lightly touched. Currently, surgical removal is the only effective treatment for pain relief. We are investigating mechanisms of tumor-induced pain. In some cases, schwannoma growth increases pressure on nearby nerves, resulting in pain. Additionally, schwannoma cells in culture secrete proinflammatory cytokines into the surrounding medium (CM) that increases neuronal sensitivity both in vitro and in vivo. When injected into a mouse hind paw, painful CM reduced paw withdrawal thresholds fourfold within one hour (p = 0.006), with effects lasting 48 h (p = 0.002) as demonstrated by Von Frey assay. We developed a chronic SWN pain model showing neuronal priming by SWN CM. After priming, a secondary CM exposure prolongs mechanical hypersensitivity for up to two weeks (p < 0.0001). We hypothesize this is mediated by mechanosensitive ion channels (MSCs), which respond to pressure and stretch. GsMTx-4, a selective MSC blocker, penetrates strained membranes to prevent MSC opening without affecting other channels. When co-injected with CM into the mouse paw, 10 µM GsMTx-4 prevented hypersensitivity to light touch. Moreover, GsMTx-4 reversed hyperalgesia even in the primed state, restoring withdrawal thresholds to baseline (p < 0.0001). These findings suggest that local injection of GsMTx-4 near painful tumors offers a promising, minimally invasive therapeutic approach for SWN pain. PERSPECTIVE: Pain is a confounding comorbidity in the multiple tumor syndrome schwannomatosis. Patients harbor benign peripheral nerve sheath tumors that rarely become malignant or cause neurological deficits. Yet, patients undergo numerous surgeries for the removal of painful tumors. A non-invasive treatment for tumor-related pain is in dire need. We are examining the small peptide GsMTx-4, a blocker of mechanosensitive ion channels, as a potential therapy for painful tumors in the context of schwannomatosis.

Evidence from epidemiological studies suggest that the prevalence of depression and anxiety among adults with chronic headaches is high, however, uncertainties remain about the magnitude of this comorbidity. The current meta-analysis aimed to determine the prevalence of depression and anxiety among adults with chronic headache conditions and identify factors that moderate prevalence. Four databases were searched from 2013 to 2024: CENTRAL, MEDLINE, EMBASE, and PsycINFO. Studies reporting the prevalence or clinical symptoms scores of depression or anxiety among adults with chronic headaches (i.e., headaches > 15 days/month for > 3 months) were included. Prevalence rates among individuals without a headache condition, or with an episodic headache disorder, were extracted separately for comparison purposes. Of the 37,149 initial records identified, 48 studies (N = 9582) met inclusion criteria. Clinical symptoms of depression and anxiety were present in 43.1% (95% CI: 37.8, 48.6; I = 94.52) and 45.9% (95% CI: 39.1, 52.9; I = 96.06) of adults with chronic headaches, respectively. Headache condition (p= .006) and location (p= .001) moderated the prevalence of depression but not anxiety. Compared to adults without headaches, adults with chronic headaches were 4.86 times more likely to have clinical symptoms of depression, and 7.06 times more likely to have clinical symptoms of anxiety. Similarly, they were 2.45 and 2.20 times more likely to have clinical symptoms of depression and anxiety, respectively, compared to individuals with episodic headaches. Almost half of adults with chronic headaches experience comorbid depression or anxiety, highlighting the urgent need for better mental health screening and treatment.

Anger is prevalent in chronic pain (CP), often co-occurring with heightened distress and disability. The complexity of the anger construct manifests in heterogeneity of how anger is experienced, expressed, and regulated. Nevertheless, most work does not consider the inter-relationships between multiple dimensions of anger, limiting understanding of how anger might differentially contribute to pain outcomes. Here, various anger metrics and latent profile analysis (LPA) were utilized to identify disparate anger profiles in people with CP. Whether these profiles associated cross-sectionally and longitudinally with pain outcomes was subsequently examined. Data was collected from 735 treatment-seeking adult patients with CP of varied etiologies, of which 242 also completed follow-up assessments about 5 months after baseline. Anger measures included state and trait anger, anger expression (anger-in, anger-out), anger control (control-in, control-out), and perceived injustice. Pain outcomes included pain- intensity, distribution, interference, and behavior, and physical function. LPA identified four distinct anger profiles characterized by the combination of varying levels (low, medium, high) of anger and of perceived injustice. These profiles significantly associated with pain outcomes at both baseline and follow-up, above and beyond anxiety and depression. Profiles with medium-to-high levels of both anger (state, trait, and expression) and perceived injustice predicted the worst pain outcomes, suggesting that injustice-based profiling should be prioritized for anger-related stratification of risk in CP. The mechanistic and prognostic value of these anger profiles suggests that early assessment could enhance long-term treatment planning and advance personalized pain care, further emphasizing the need for tailored, anger-focused, patient-specific interventions. PERSPECTIVES: This study demonstrates that multidimensional anger profiles, particularly those marked by higher perceived injustice, are linked to more severe and persistent high impact chronic pain. Identifying these profiles may facilitate early clinical screening for at-risk patients, personalized emotion-focused interventions, and potentially prevent progression to high-impact chronic pain and long-term disability.

The family of transmembrane channel-like (TMC) genes encodes at least 8 transmembrane proteins that are conserved across species. However, except for TMC1 and TMC2, their functional role is largely unexplored. To determine the extent to which each of these subtypes contributes to pain and itch processing, here we investigated the anatomical and behavioral consequences of deleting 3 members of the TMC family in mice. We report that selective ablation of the Tmc3, Tmc5 or Tmc7 genes leads to different, and in some cases, opposite behavioral effects. Specifically, mice deficient for Tmc3 or Tmc5 exhibited reduced nociception across pain modalities (mechanical, heat and cold), whereas Tmc7 deletion increased nociception. With respect to itch, pruritogen-evoked scratching was increased in Tmc5 and Tmc7, but not Tmc3 knock-out mice. Interestingly, although the expression of Tmc3, Tmc5 and Tmc7 was upregulated in sensory neurons of mice in the spared nerve injury (SNI) model of neuropathic pain, ablating these genes did not prevent the mechanical allodynia that develops following SNI. Responses also did not change in an inflammatory pain setting. Taken together, we conclude that TMC3, TMC5 and TMC7 channels differentially contribute to pain and itch processing. The mechanisms underlying these differences remain to be determined. PERSPECTIVE: Tmc3 and Tmc5 knock-out mice exhibit decreased nociception; Tmc7 knock-out mice exhibit increased nociception; Tmc5 and Tmc7, but not Tmc3, contribute to itch processing.

Pain and symptoms of depression and anxiety (here, 'psychological distress') are frequently reported by people with HIV. Although pain is widely acknowledged to contribute to distress, distress may also contribute to pain and its persistence. Facilitation of nociceptive signalling is one pathway by which distress could exacerbate pain. The current study investigated the relationships between symptoms of depression and anxiety, secondary hyperalgesia (SH), and persistent pain in people with HIV, reporting pain (n=19) or no pain (n=26). We hypothesised that self-reported distress would be positively associated with the surface area (primary measure) and magnitude (secondary measure) of induced SH, and that participants reporting persistent pain would display greater induced SH than those reporting no pain. We found that distress was positively associated with the surface area (p=0.02) and the magnitude (p=0.01) of induced SH. However, participants with persistent pain showed no difference in the surface area of SH compared to pain-free participants (p=0.87), and those with pain displayed a marginally lower magnitude of SH (p=0.05). These findings position SH as a potentially useful mechanistic outcome for interventions that aim to address pain by reducing symptoms of depression and anxiety. PERSPECTIVE: Symptoms of depression and anxiety were positively associated with induced secondary hyperalgesia in people with suppressed HIV.

Posttraumatic stress disorder (PTSD) and chronic pain are highly comorbid, share overlapping symptoms, and exacerbate and maintain one another, which makes the accurate assessment of symptoms critical to effective clinical care. The present study evaluated the factor structure of the PTSD Checklist for DSM-5 (PCL-5) in a veteran sample with chronic pain and determined the extent to which pain intensity is associated with PCL-5 responses. Participants were a national sample of 384 veterans prescribed long-term opioid therapy who reported moderate or severe pain, experienced a traumatic event, and completed the PCL-5. The majority of the sample identified as White (79.9%) and Male (84.1%). Confirmatory factor analysis was used to evaluate the factor structure of the PCL-5, and measurement invariance testing was used to determine the extent to which pain intensity was associated with how patients responded to the PCL-5. The six-factor anhedonia (χ= 313.45, df = 155, CFI =.969, RMSEA =.052, 90% CI:.043,.060, DRMR =.036, TLI =.95) and seven-factor hybrid (χ= 304.20, df = 149, CFI =.960, RMSEA =.052, 90% CI:.044,.060, SRMR =.036, TLI =.95) models emerged as the best fitting and both exhibited configural, metric and scalar invariance. This suggests that PCL-5 scores can be interpreted similarly among patients with moderate and severe chronic pain and that complex models can be employed to help determine the focus of treatment and track granular changes in PTSD symptoms over time. PERSPECTIVE: In a sample of veterans with chronic pain, this article evaluates the factor structure of the PCL-5 and whether it is invariant across different levels of pain intensity. The PCL-5 shows similar psychometric properties regardless of pain intensity, which is important for its continued use in research and clinical settings.

Prior literature has shown inequities in patient-clinician interactions experienced by individuals with chronic low back pain (CLBP) with underlying pain-related stigmatization and invalidation. Yet, there is a notable gap in understanding how these inequities intersect with multiple systems of oppression, including racism and sexism. This qualitative study examined intersectional perspectives and experiences of patient-clinician interactions among individuals with CLBP. Semi-structured interviews were conducted after the participants engaged in simulated enhanced or limited patient-clinician interactions as part of an experimental study. Participants were asked to compare the simulated patient-clinician interaction to their real-life patient-clinician interactions for their CLBP. The study included 50 participants with CLBP for at least three months and half the days in the past six months. Participants were Black and multi-racial women (n=14), Black and multi-racial men (n=12), non-Hispanic White women (n=12), and non-Hispanic White men (n=12). A basic qualitative approach with principles from constructivist grounded theory and intercategorical intersectional research were used to propose three core categories when describing inequities in patient-clinician interactions: higher-level systems (subcategories: institutional, community, macro-level), the patient-clinician interaction (subcategories: being taken seriously, person-centered care), and effects of the patient-clinician interaction (subcategories: indirect, direct effects). Inequities were identified across all categories, disproportionately affecting Black and multi-racial women. Black and multi-racial women also distinctly shared a wider range of both positive and negative patient-clinician interactions and effects from these interactions, and potential pathways to more equitable care. These findings highlight the need for multi-level interventions to promote more equitable care for individuals with CLBP. PERSPECTIVE: This qualitative study examined intersectional perspectives and experiences of patient-clinician interactions among individuals with CLBP. Multiple intersecting systems shaped inequities in patient-clinician interactions. Black and multi-racial women shared the broadest range of patient-clinician interactions, distinctly discussed intersecting systems of oppression, and highlighted pathways to more equitable care.

Numerous studies have demonstrated diurnal rhythms of pain sensitivity in humans, yet only one has shown an endogenous circadian heat pain rhythmicity using a constant routine procedure, a well-validated chronobiological technique. Establishing the circadian rhythm of pain sensitivity is an important first step for optimizing pain assessment and personalizing pain management strategies. The present study extended this work by employing a 26-hour ultrashort sleep-wake protocol, another validated and less invasive chronobiological method, to examine circadian regulation of mechanical (pressure) pain sensitivity in 23 healthy adults (18 males, 5 females; mean age = 29.7). All participants completed the 26-hour ultrashort sleep-wake protocol (2-hour wake/1-hour sleep cycle) that evenly distributes circadian masking factors (e.g., sleep, light, food intake, and physical activity). Pressure pain threshold was assessed nine times across the 26-hour period. Cosinor analysis revealed a strong circadian rhythm (R² = 0.93), indicating that 93% of variance in pressure pain threshold scores over time were accounted for by circadian rhythmicity. The acrophase (highest pressure path threshold, indicating lowest mechanical pain sensitivity) occurred at 1:44 PM, and the nadir (lowest pressure pain threshold, indicating highest mechanical pain sensitivity) at 1:44 AM. The amplitude of the circadian rhythm was 0.62, representing a large 1.24 z-score difference in mechanical pain sensitivity between the peak and nadir. These findings confirm previous work and further demonstrate a clear endogenous circadian rhythm in mechanical pain sensitivity. This rhythmicity has several important implications for pain assessment, clinical procedures, and chronotherapy in pain management. PERSPECTIVES: Using a 26-hour ultrashort sleep-wake protocol, a validated chronobiological technique, the authors identified a clear and robust circadian rhythm in mechanical pain sensitivity among healthy adults. These findings highlight the importance of considering circadian timing in pain assessment and may inform future approaches to personalized pain medicine.

As pain persists, individuals with chronic pain must draw upon resilience resources to improve physical function and emotional well-being. Leading theoretical models highlight positive emotions as central to the process of pain-related resilience. This ecological momentary assessment (EMA) study investigated the role of savoring-a positive emotion upregulation strategy-in the daily experience of pain among individuals with chronic low back pain (CLBP) who had not received prior training in savoring or other emotion regulation strategies. Of the 135 participants included in the study, 81 were maintained on long-term opioid therapy (LTOT), permitting further investigation of the associations between savoring and opioid analgesia. Across 14 days of EMA (3,367 total observations), greater momentary savoring was concurrently and prospectively associated with lower pain severity. Momentary savoring was also associated with greater opioid analgesia, particularly when participants reported taking lower opioid doses than usual. The effects of savoring on both pain and opioid analgesia were mediated by increased positive affect. Collectively, the findings provide a mechanistic framework for how patients with chronic pain naturally utilize savoring as a positive emotion upregulation strategy to promote daily resilience to chronic pain. Future work is needed to determine which individuals are most likely to experience pain relief as a result of savoring, the circumstances in which savoring is most likely to be adopted as a pain self-management tool, and how to most efficiently and effectively intervene to promote savoring in the course of daily life with chronic pain. PERSPECTIVE: This microlongitudinal study demonstrates the naturalistic use of savoring, an emotional upregulation strategy, improves momentary and future pain severity ratings in those with chronic low back pain. Savoring was related to improved responses to opioid medication use, with increasing positive affect mediating the effects of savoring on opioid associated analgesia.

Post-Traumatic Stress Disorder (PTSD) and chronic pain frequently co-occur and are known to mutually exacerbate one another, yet, the mechanisms connecting PTSD to chronic pain are less clear. The purpose of this systematic review and meta-analysis was to identify and quantify psychosocial factors that mediate the bidirectional relationship between PTSD and chronic pain. Five databases (PubMed, Cochrane Central Register of Controlled Trials, CINAHL Complete, PsychINFO, and Web of Science) were searched from inception through December 17th 2024. Mediation studies which examined the relationship between PTSD and pain severity or physical interference among adults with chronic pain were included. Standardized indirect regression coefficients (β) were pooled and served as the primary outcome. Of the 5359 articles identified, 14 studies met inclusion criteria. Pain catastrophizing mediated the relationship between PTSD and pain severity (K = 3; β =.18, 95% CI:.12,.26) while depression mediated the relationship between PTSD and physical interference (K = 3; β = 1.25, 95% CI:.04, 2.46) but not pain severity (K = 4; β =.18, 95% CI: -.10,.47). These results should be interpreted with caution as all identified studies were cross-sectional and their methodological quality was low. More methodically rigorous longitudinal studies are needed to better understand the putative mechanisms connecting PTSD to chronic pain. PROTOCOL REGISTRATION: PROSPERO#: CRD42024608251 PERSPECTIVE: This systematic review and meta-analysis examined psychosocial mechanisms that explain the bidirectional relationship between PTSD and chronic pain. There was preliminary evidence that PTSD is indirectly associated with chronic pain via pain catastrophizing and depression. Additional longitudinal research is needed to increase our understanding of putative mechanisms connecting both conditions.