Preliminary Validation of the Pain Relief Motivation Scales.

OBJECTIVES: Pain typically prompts individuals to seek relief. This study aimed to develop and psychometrically validate the Pain Relief Motivation Scales, applying revised "reinforcement sensitivity theory" to measure the neuropsychological systems underlying motivation for pain relief. We hypothesized a 6-factor structure based on previous work, including one Behavioral Inhibition System (BIS) factor, one Fight-Flight-Freeze System factor, and 4 Behavioral Activation System (BAS) factors. METHODS: Items were generated by adapting the reinforcement sensitivity theory of personality questionnaire for relevance to pain relief. Adults with chronic pain were recruited internationally to participate in online survey batteries at baseline and 1 week later in 2021. We randomly split the sample to conduct exploratory factor analysis (n = 253) and confirmatory factor analysis (n = 253). Psychometric properties were estimated using the full sample (N = 506). RESULTS: Parallel analysis revealed that a 5-factor structure best fits the data (21 items): (1) hopelessness about pain relief (BIS), (2) hesitancy for engaging in pain treatments (BIS), (3) persistence in engaging in pain treatments (BAS), (4) relief reactivity (BAS), and (5) risky relief seeking (BAS). Acceptable internal consistency (Cronbach alpha = 0.68 to 0.80) and test-retest reliability (Intraclass correlation coefficients = 0.71 to 0.88) were observed. Construct validity varied from weak to moderate ( r = 0.02 to 0.45). CONCLUSION: As the first attempt to create an instrument measuring neuropsychological systems underlying motivation for pain relief, the findings show that additional work is needed to refine theory and psychometric rigor in this area. Cautiously, the results suggest that a BIS-BAS model, with minimal Fight-Flight-Freeze System contributions, might be useful for understanding the motivation for relief.

Developing consensus on core outcome sets of domains for acute, the transition from acute to chronic, recurrent/episodic, and chronic pain: results of the INTEGRATE-pain Delphi process.

Background: Pain is the leading cause of disability worldwide among adults and effective treatment options remain elusive. Data harmonization efforts, such as through core outcome sets (COS), could improve care by highlighting cross-cutting pain mechanisms and treatments. Existing pain-related COS often focus on specific conditions, which can hamper data harmonization across various pain states. Methods: Our objective was to develop four overarching COS of domains/subdomains (i.e., what to measure) that transcend pain conditions within different pain categories. We hosted a meeting to assess the need for these four COS in pain research and clinical practice. Potential COS domains/subdomains were identified via a systematic literature review (SLR), meeting attendees, and Delphi participants. We conducted an online, three step Delphi process to reach a consensus on domains to be included in the four final COS. Survey respondents were identified from the SLR and pain-related social networks, including multidisciplinary health care professionals, researchers, and people with lived experience (PWLE) of pain. Advisory boards consisting of COS experts and PWLE provided advice throughout the process. Findings: Domains in final COS were generally related to aspects of pain, quality of life, and physical function/activity limitations, with some differences among pain categories. This effort was the first to generate four separate, overarching COS to encourage international data harmonization within and across different pain categories. Interpretation: The adoption of the COS in research and clinical practice will facilitate comparisons and data integration around the world and across pain studies to optimize resources, expedite therapeutic discovery, and improve pain care. Funding: Innovative Medicines Initiative 2 Join Undertaking; European Union Horizon 2020 research innovation program, European Federation of Pharmaceutical Industries and Associations (EFPIA) provided funding for IMI-PainCare. RDT acknowledges grants from Esteve and TEVA.

Racism exposure and trauma accumulation perpetuate pain inequities-advocating for change (RESTORATIVE): A conceptual model.

Experiences of racism occur across a continuum from denial of services to more subtle forms of discrimination and exact a significant toll. These multilevel systems of oppression accumulate as chronic stressors that cause psychological injury conceptualized as racism-based traumatic stress (RBTS). RBTS has overlapping symptoms with posttraumatic stress disorder (PTSD) with the added burden that threats are constantly present. Chronic pain is a public health crisis that is exacerbated by the intersection of racism and health inequities. However, the relationship between RBTS and pain has not yet been explored. To highlight how these phenomena are interlinked, we present Racism ExpoSure and Trauma AccumulatiOn PeRpetuate PAin InequiTIes-AdVocating for ChangE (RESTORATIVE); a novel conceptual model that integrates the models of racism and pain and demonstrates how the shared contribution of trauma symptoms (e.g., RBTS and PTSD) maintains and perpetuates chronic pain for racialized groups in the United States. Visualizing racism and pain as "two halves of the same coin," in which the accumulative effects of numerous events may moderate the severity of RBTS and pain, we emphasize the importance of within-group distinctiveness and intersectionality (overlapping identities). We call on psychologists to lead efforts in applying the RESTORATIVE model, acting as facilitators and advocates for the patient's lived experience with RBTS in clinical pain care teams. To assist with this goal, we offer suggestions for provider and researcher antiracism education, assessment of RBTS in pain populations, and discuss how cultural humility is a central component in implementing the RESTORATIVE model. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Preliminary Evidence for the Sequentially Mediated Effect of Racism-Related Stress on Pain Sensitivity Through Sleep Disturbance and Corticolimbic Opioid Receptor Function.

Sleep disturbance predicts worse pain outcomes. Because sleep disturbance inequitably impacts Black adults - with racism as the upstream cause - understanding how racism-related stress impacts pain through sleep might help minimize racialized pain inequities. This preliminary study examined sequential mediation of the effect of racism-related stress on experimental pain through sleep disturbance and corticolimbic µOR function in pain-free non-Hispanic Black (NHB) and White (NHW) adults. Participants completed questionnaires, actigraphy, positron emission tomography, and sensory testing. We reproduced findings showing greater sleep disturbance and pain sensitivity among NHB participants; greater sleep disturbance (r = .35) and lower pain tolerance (r=-.37) were significantly associated with greater racism-related stress. In a sequential mediation model, the total effect of racism-related stress on pain tolerance (ß=-.38, P = .005) weakened after adding sleep disturbance and ventromedial prefrontal cortex (vmPFC) µOR binding potential (BPND) as mediators (ß = -.18, P = .16). The indirect effect was statistically significant [point estimate = -.003, (-.007, -.0003). Findings showed a potential sequentially mediated effect of racism-related stress on pain sensitivity through sleep disturbance and vmPFC µOR BPND. As policy efforts are enacted to eliminate the upstream cause of systemic racism, these results cautiously suggest that sleep interventions within racism-based trauma informed therapy might help prevent downstream effects on pain. PERSPECTIVE: This preliminary study identified the effect of racism-related stress on pain through sleep disturbance and mu-opioid receptor binding potential in the ventromedial prefrontal cortex. Findings cautiously support the application of sleep interventions within racism-based trauma-informed therapy to prevent pain inequities as policy changes function to eliminate all levels of racism.

Depressive and Insomnia Symptoms Sequentially Mediate the Association Between Racism-Based Discrimination in Healthcare Settings and Clinical Pain Among Adults With Sickle Cell Disease.

Racism-based discrimination in healthcare settings has been associated with clinical pain in adults living with sickle cell disease; however, no studies have examined depressive and insomnia symptoms as mechanisms that may drive this relationship. This secondary data analysis examined associations between depressive and insomnia symptoms, racism-based discrimination, and clinical pain. Seventy-one adults with sickle cell disease (70% female, Mage = 38.79) provided baseline reports of racism-based discrimination, depressive symptoms, insomnia symptoms, and pain (severity, interference, catastrophizing), and they completed daily diaries of pain severity and interference over 3 months. In a sequential mediation model, baseline depressive (1st) and insomnia symptoms (2nd) significantly mediated the association between racism-based discrimination and baseline pain interference, average daily diary pain severity, and average daily diary pain interference. Although the mediation model with baseline pain severity as the outcome was significant, the total and direct effects were not. Results indicate that discrimination in healthcare settings contributes to depression, which may act on pain through sleep disturbance. Findings support the need for systemic and structural changes to eliminate discrimination in healthcare settings and behavioral mood and sleep interventions to reduce the impact of discrimination on clinical pain. PERSPECTIVE: The relationship between discrimination in healthcare settings and pain in adults with sickle cell disease may be driven by depression and sleep disturbance, modifiable risk factors and potential treatment targets. Results suggest that systemic, structural, and institutional changes must be implemented to promote better patient care and health outcomes.

Meditation Practice, Mindfulness, and Pain-Related Outcomes in Mindfulness-Based Treatment for Episodic Migraine.

Objectives: Mindfulness-based interventions (MBIs) have emerged as promising prophylactic episodic migraine treatments. The present study investigated biopsychosocial predictors and outcomes associated with formal, daily-life meditation practice in migraine patients undergoing MBI, and whether augmented mindfulness mechanistically underlies change. Methods: Secondary analyses of clinical trial data comparing a 12-week enhanced mindfulness-based stress reduction course (MBSR + ; n = 50) to stress management for headache (SMH; n = 48) were conducted. Results: Pre-treatment mesocorticolimbic system functioning (i.e., greater resting state ventromedial prefrontal cortex-right nucleus accumbens [vmPFC-rNAC] functional connectivity) predicted greater meditation practice duration over MBSR + (r = 0.58, p = 0.001), as well as the change in headache frequency from pre- to post-treatment (B = -12.60, p = 0.02) such that MBSR + participants with greater vmPFC-rNAC connectivity showed greater reductions in headache frequency. MBSR + participants who meditated more showed greater increases in mindfulness (B = 0.52, p = 0.02) and reductions in the helplessness facet of pain catastrophizing (B = -0.13, p = 0.01), but not headache frequency, severity, or impact. Augmented mindfulness mediated reductions in headache impact resulting from MBSR + , but not headache frequency. Conclusions: Mesocorticolimbic system function is implicated in motivated behavior, and thus, motivation-enhancing interventions might be delivered alongside mindfulness-based training to enhance meditation practice engagement. Formal, daily-life meditation practice duration appears to benefit pain-related cognitions, but not clinical pain, while mindfulness emerges as a mechanism of MBIs on headache impact, but not frequency. Further research is needed to investigate the day-to-day effects of formal, daily-life meditation practice on pain, and continue to characterize the specific mechanisms of MBIs on headache outcomes. Preregistration: This study is not preregistered.

Is Mindfulness Associated With Lower Pain Reactivity and Connectivity of the Default Mode Network? A Replication and Extension Study in Healthy and Episodic Migraine Participants.

Formal training in mindfulness-based practices promotes reduced experimental and clinical pain, which may be driven by reduced emotional pain reactivity and undergirded by alterations in the default mode network, implicated in mind-wandering and self-referential processing. Recent results published in this journal suggest that mindfulness, defined here as the day-to-day tendency to maintain a non-reactive mental state in the absence of training, associates with lower pain reactivity, greater heat-pain thresholds, and resting-state default mode network functional connectivity in healthy adults in a similar manner to trained mindfulness. The extent to which these findings extend to chronic pain samples and replicate in healthy samples is unknown. Using data from healthy adults (n = 36) and episodic migraine patients (n = 98) and replicating previously published methods, we observed no significant association between mindfulness and heat-pain threshold, pain intensity or unpleasantness, or pain catastrophizing in healthy controls, or between mindfulness and headache frequency, severity, impactor pain catastrophizing in patients. There was no association between default mode network connectivity and mindfulness in either sample when probed via seed-based functional connectivity analyses. In post-hoc whole brain exploratory analyses, a meta-analytically derived default mode network node (ie, posterior cingulate cortex) showed connectivity with regions unassociated with pain processing as a function of mindfulness, such that healthy adults higher in mindfulness showed greater functional connectivity between the posterior cingulate cortex-and cerebellum. Collectively, these findings suggest that the relationship between mindfulness and default mode network functional connectivity may be nuanced or non-robust, and encourage further investigation of how mindfulness relates to pain. PERSPECTIVE: This study found few significant associations between dispositional mindfulness and pain, pain reactivity and default mode connectivity in healthy adults and migraine patients. The relationship between mindfulness and default mode network connectivity may be nuanced or non-robust.

Confronting Racism in All Forms of Pain Research: Reframing Study Designs.

This second paper in a 3-part series on antiracism in pain research across the translational spectrum focuses on study design factors. Although objectivity is a cornerstone value of science, subjectivity is embedded in every step of the research process as investigators make choices about who they collaborate with, which research questions they ask, how they recruit participants, which research tools they use, and how they analyze and interpret data. We present theory and evidence from disciplines such as sociology, medical anthropology, statistics, and public health to discuss 4 common study design factors, including 1) the dominant biomedical narrative of pain that restricts funding and exploration of social indicators of pain, 2) low diversity and inclusion in pain research enrollment that restricts generalizability to racialized groups, 3) the use of "race" or "ethnicity" as a statistical variable and proxy for lived experiences (eg, racism, resilience), and 4) limited modeling in preclinical research for the impact of social factors on pain physiology. The information presented in this article is intended to start conversations across stakeholders in the pain field to explore how we can come together to adopt antiracism practices in our work at large to achieve equity for racialized groups. PERSPECTIVE: This is the second paper in a 3-part series on antiracism in pain research. This part identifies common study design factors that risk hindering progress toward pain care equity. We suggest reframes using an antiracism framework for these factors to encourage all pain investigators to collectively make strides toward equity.

Confronting Racism in Pain Research: A Call to Action.

Racism is an established health determinant across the world. In this 3-part series, we argue that a disregard of how racism manifests in pain research practices perpetuates pain inequities and slows the progression of the field. Our goal in part-1 is to provide a historical and theoretical background of racism as a foundation for understanding how an antiracism pain research framework - which focuses on the impact of racism, rather than "race," on pain outcomes - can be incorporated across the continuum of pain research. We also describe cultural humility as a lifelong self-awareness process critical to ending generalizations and successfully applying antiracism research practices through the pain research continuum. In part-2 of the series, we describe research designs that perpetuate racism and provide reframes. Finally, in part-3, we emphasize the implications of an antiracism framework for research dissemination, community-engagement practices and diversity in research teams. Through this series, we invite the pain research community to share our commitment to the active process of antiracism, which involves both self-examination and re-evaluation of research practices shifting our collective work towards eliminating racialized injustices in our approach to pain research. PERSPECTIVE: We call on the pain community to dismantle racism in our research practices. As the first paper of the 3-part series, we introduce dimensions of racism and its effect on pain inequities. We also describe the imperative role of cultural humility in adopting antiracism pain research practices.

Confronting Racism in All Forms of Pain Research: A Shared Commitment for Engagement, Diversity, and Dissemination.

This third paper in the "Confronting Racism in All Forms of Pain Research" series discusses adopting an antiracism framework across all pain research disciplines and highlights the significant benefits of doing so. We build upon the previous call to action and the proposed reframing of study designs articulated in the other papers in the series and seek to confront and eradicate racism through a shared commitment to change current research practices. Specifically, we emphasize the systematic disadvantage created by racialization (ie, the Eurocentric social and political process of ascribing racialized identities to a relationship, social practice, or group) and discuss how engaging communities in partnership can increase the participation of racialized groups in research studies and enrich the knowledge gained. Alongside this critical work, we indicate why diversifying the research environment (ie, research teams, labs, departments, and culture) enriches our scientific discovery and promotes recruitment and retention of participants from racialized groups. Finally, we recommend changes in reporting and dissemination practices so that we do not stigmatize or reproduce oppressive forms of power for racialized groups. Although this shift may be challenging in some cases, the increase in equity, generalizability, and credibility of the data produced will expand our knowledge and reflect the pain experiences of all communities more accurately. PERSPECTIVE: In this third paper in our series, we advocate for a shared commitment toward an antiracism framework in pain research. We identify community partnerships, diversification of research environments, and changes to our dissemination practices as areas where oppressive forms of power can be reduced.

Racial disparities in sleep-related cardiac function in young, healthy adults: implications for cardiovascular-related health.

STUDY OBJECTIVES: Considerable evidence shows that individuals from marginalized racial/ethnic groups in the United States experience greater rates of sleep disturbance and cardiovascular complications. Because sleep is a modifiable factor that is critically involved in cardiovascular health, improved understanding of the association between sleep and cardiovascular health during early adulthood can prevent cardiovascular disparities. This study examined racial/ethnic differences in cardiovascular function during sleep using heart rate and heart-rate-variability analyses. METHODS: Participants in this laboratory-based sleep study included healthy, "good sleepers" who were in early adulthood and resided in the United States at the time of participation (14 non-Hispanic Black [NHB; age = 30.9 (6.6), 57% female], 12 Asian [Asian, age = 26.0 (5.2), 42% female], and 24 non-Hispanic white [NHW; age = 24.6 (5.8), 79% female]). RESULTS: After adjusting for demographic factors and an apnea-hypopnea index, we found significantly higher heart rate within NREM Stage 2 (N2) (b = -22.6, p = .04) and REM sleep (b = -25.8, p =.048) and lower heart rate variability during N2 sleep (b = -22.6, p = .04) among NHB individuals compared with NHW individuals. Furthermore, NHB and Asian participants demonstrated significantly lower percent of time in slow wave sleep (SWS) compared with NHW participants (NHB: b = -22.6, p =.04; Asian: b = -22.6, p = .04). Individuals' percent of time in SWS significantly mediated differences in heart rate during N2 (indirect = 0.94, 95% CI [0.03, 2.68]) and REM sleep (indirect = 1.02, 95% CI [0.04, 3.04]). CONCLUSIONS: Our results showed disparities in sleep-related cardiovascular function in early adulthood that are mediated by SWS. These data suggest targeting sleep health in early adulthood might help reduce cardiovascular disease burden on individuals from marginalized groups.

Temporal Association of Pain Catastrophizing and Pain Severity Across the Perioperative Period: A Cross-Lagged Panel Analysis After Total Knee Arthroplasty.

OBJECTIVE: Although numerous studies show that preoperative pain catastrophizing is a risk factor for pain after total knee arthroplasty (TKA), little is known about the temporal course of the association between perioperative pain catastrophizing and pain severity. The present study investigated temporal changes and their dynamic associations between pain catastrophizing and pain severity before and after TKA. DESIGN: A secondary data analysis of a larger observational parent study featuring prospective repeated measurement over 12 months. SETTING: Dual-site academic hospital. SUBJECTS: A total of 245 individuals who underwent TKA. METHODS: Participants completed pain catastrophizing and pain severity questionnaires at baseline, 6 weeks, and 3, 6, and 12 months after TKA. Cross-lagged panel analysis was conducted with structural equation modeling including age, sex, race, baseline anxiety, and depressive symptoms as covariates. RESULTS: Reduction in pain catastrophizing from baseline to 6 weeks after TKA was associated with lower pain severity at 3 months after TKA (standardized ß = 0.14; SE = 0.07, P = 0.046), while reduction in pain severity at 6 weeks after TKA was not associated with pain catastrophizing at 3 months after TKA (P = 0.905). In the chronic postsurgical period (>3 months), pain catastrophizing at 6 months after TKA predicted pain severity at 12 months after TKA (ß = 0.23, P = 0.009) with controlling for auto-correlation and covariates, but not vice versa. CONCLUSIONS: We provide evidence that changes in pain catastrophizing from baseline to 6 weeks after TKA are associated with subsequent pain severity. Future studies are warranted to determine whether targeting pain catastrophizing during the perioperative period may improve clinical outcomes for individuals undergoing TKA.

Ethnic Differences in Experimental Pain Responses Following a Paired Verbal Suggestion With Saline Infusion: A Quasiexperimental Study.

BACKGROUND: Ethnic differences in placebo and nocebo responses are an important, yet underresearched, patient factor that might contribute to treatment disparities. PURPOSE: The purpose of this study was to examine ethnic differences in pain trajectories following a verbal suggestion paired with a masked, inert substance (i.e., saline). METHODS: Using a quasiexperimental design, we examined differences between 21 non-Hispanic Black (NHB) participants and 20 non-Hispanic White (NHW) participants in capsaicin-related pain rating trajectories following a nondirectional verbal suggestion + saline infusion. All participants were told that the substance would "either increase pain sensation, decrease it, or leave it unchanged." A spline mixed model was used to quantify the interaction of ethnicity and time on ratings. RESULTS: There was a significant Ethnicity × Time interaction effect (ß = -0.28, p = .002); NHB individuals reported significantly greater increases in pain following, but not before, the verbal suggestion + saline infusion. Sensitivity analyses showed no change in primary results based on differences in education level, general pain sensitivity, or condition order. CONCLUSIONS: The present results showed ethnic differences in pain response trajectories following a verbal suggestion + saline infusion and suggest that future research rigorously examining possible ethnic differences in placebo/nocebo responses is warranted.

Craving mediates the association between momentary pain and illicit opioid use during treatment for opioid-use disorder: an ecological momentary assessment study.

AIM: To assess the role of momentary pain on opioid craving and illicit opioid use among individuals receiving opioid agonist treatment. DESIGN: Observational study using ecological momentary assessment. SETTING: The National Institute of Drug Abuse Intramural Research Program in the United States. PARTICIPANTS: Fifty-six adults who qualified for opioid agonist treatment. MEASUREMENTS: Participants completed randomly prompted assessments of pain severity, stress, negative mood, opioid craving and illicit opioid use for a mean of 66 days [standard deviation (SD) = 27]. Urine samples were collected two to three times/week throughout. FINDINGS: Almost 70% of participants reported moderate average pain severity in the past 24 hours at intake and 35% of participants reported chronic pain. There were no significant differences in percent of opioid-positive urine samples (P = 0.73) and average level of opioid craving during the study period (P = 0.91) among opioid agonist treatment only patients versus opioid agonist treatment patients with chronic pain. However, momentary pain severity significantly predicted concurrent opioid craving [B = 0.02, 95% confidence interval (CI) = 0.01, 0.04], over and above stress and negative mood. Momentary opioid craving, in turn, significantly predicted illicit opioid use that was assessed in the next moment [odds ratio (OR) = 1.72, 95% CI = 1.12, 2.64), while controlling for autocorrelation and the effects of pain, negative mood and stress. Momentary opioid craving significantly mediated the prospective association between momentary pain and illicit opioid use (95% CI = 0.003, 0.032). Exploratory analysis revealed that momentary pain severity also significantly moderated the momentary association between stress and opioid craving (B = 0.02, 95% CI = 0.00, 0.04), such that when momentary pain severity increased, the association between the two intensified. CONCLUSIONS: Among people receiving opioid agonist treatment, momentary pain appears to be indirectly associated with illicit opioid use via momentary opioid craving.

Experimenter- and Infrared Thermography-Derived Measures of Capsaicin-Induced Neurogenic Flare Among Non-Hispanic White and Black Adults.

OBJECTIVE: Capsaicin is a widely utilized experimental pain stimulus; however, few studies have reported on ethnic differences in pain responses to capsaicin. The present study used infrared thermography to 1) measure differences in capsaicin-induced neurogenic flare between non-Hispanic black (NHB) and non-Hispanic white (NHW) adults and 2) determine the association between neurogenic flare and secondary hyperalgesia. METHODS: Fifty-four participants (NHB N = 28) underwent heat/capsaicin sensitization model procedures. Neurogenic flare was examined using experimenter (i.e., subjective) and thermography (i.e., objective) measurements. A typically nonpainful mechanical punctate probe was used to measure secondary hyperalgesia. RESULTS: Ethnic groups did not significantly differ in age, sex, marital status, or personal income. Although experimenters rated a significantly wider area of capsaicin-related neurogenic flare among NHW compared with NHB participants (F1, 52 = 8.33, P = 0.006), thermography results showed no differences between groups in neurogenic flares (F1, 52 = 0.01, P = 0.93). Further, although NHB individuals reported greater average pain during the capsaicin procedures compared with NHW individuals (NHB = 58.57 [3.67], NHW = 46.46 [3.81]; F2, 51 = 5.19, P = 0.03), the groups did not differ in secondary hyperalgesia (F2, 51 = 0.03, P = 0.86), and ethnicity did not moderate the association between neurogenic flare and secondary hyperalgesia (F3, 50 = 0.24, P = 0.87). CONCLUSIONS: Findings cautiously support the use of infrared thermography over subjective experimenter report when measuring neurogenic inflammation in diverse samples. However, infrared thermography should not be used as a diagnostic tool for pain, given the lack of association between these factors. Future research is warranted to replicate these findings in a larger and more diverse sample to determine accurate neurogenic inflammation measures across other ethnic minority populations.

Individual differences in pain sensitivity are associated with cognitive network functional connectivity following one night of experimental sleep disruption.

Previous work suggests that sleep disruption can contribute to poor pain modulation. Here, we used experimental sleep disruption to examine the relationship between sleep disruption-induced pain sensitivity and functional connectivity (FC) of cognitive networks contributing to pain modulation. Nineteen healthy individuals underwent two counterbalanced experimental sleep conditions for one night each: uninterrupted sleep versus sleep disruption. Following each condition, participants completed functional MRI including a simple motor task and a noxious thermal stimulation task. Pain ratings and stimulus temperatures from the latter task were combined to calculate a pain sensitivity change score following sleep disruption. This change score was used as a predictor of simple motor task FC changes using bilateral executive control networks (RECN, LECN) and the default mode network (DMN) masks as seed regions of interest (ROIs). Increased pain sensitivity after sleep disruption was positively associated with increased RECN FC to ROIs within the DMN and LECN (F(4,14) = 25.28, pFDR = 0.05). However, this pain sensitivity change score did not predict FC changes using LECN and DMN masks as seeds (pFDR > 0.05). Given that only RECN FC was associated with sleep loss-induced hyperalgesia, findings suggest that cognitive networks only partially contribute to the sleep-pain dyad.

Cannabinoid effects on responses to quantitative sensory testing among individuals with and without clinical pain: a systematic review.

There has been an explosion of interest in the utility of cannabinoids as potential analgesics. This systematic review critically synthesizes the evidence for cannabinoid analgesic effects on quantitative sensory testing outcomes in both healthy adults and patients with chronic noncancer pain. Our systematic review protocol is preregistered on PROSPERO (CRD42018117367). An electronic search was made in PsycINFO, Cochrane, Google Scholar, Embase, and Pubmed of all literature published until August 2018. Of the 1217 studies found from the search, a total 39 placebo-controlled studies that met the eligibility criteria were synthesized for this study. Because of substantial heterogeneity of study designs, populations, cannabinoid compounds, and quantitative sensory testing outcomes, meta-analysis was not conducted. More consistent evidence of cannabinoid analgesia was observed for inhaled cannabis than synthetic cannabinoids. Analgesic effects were most commonly observed in tests of cold pain sensitivity, and hyperalgesic effects were most commonly observed in tests of electrical stimulation. Patterns of findings from studies with healthy subjects did not substantively differ from those with chronic noncancer pain. However, these observations are qualified by the high degree of inconsistency across studies and methodological heterogeneity. We offer recommendations for future studies to improve study rigor and reproducibility.

Sex Differences in Interleukin-6 Responses Over Time Following Laboratory Pain Testing Among Patients With Knee Osteoarthritis.

Epidemiological studies suggest that women are not only at a higher risk for developing knee osteoarthritis (KOA), but also report greater symptom severity compared to men. One potential underlying mechanism of these sex differences may be exaggerated inflammatory responses to pain among women compared to men. The present study examined sex differences in interleukin-6 (IL-6) response over time following experimental pain testing. We hypothesized that women, when compared to men, would show greater IL-6 reactivity when exposed to acute pain in a human laboratory setting. Eighty-four participants (36 men and 48 women) with KOA scheduled for total knee arthroplasty underwent a quantitative sensory testing (QST) battery. A total of seven IL-6 measurements were taken, twice at baseline, once immediately after QST, and every 30 minutes up to 2 hours after QST. Consistent with our hypothesis, women, when compared to men, showed accelerated increases in IL-6 levels following laboratory-evoked pain, even after controlling for body mass index, marital status, clinical pain, evoked pain sensitivity, and situational pain catastrophizing. Given that KOA is a chronic condition, and individuals with KOA frequently experience pain, these sex differences in IL-6 reactivity may contribute to the maintenance and/or exacerbation of KOA symptoms. PERSPECTIVES: The present study demonstrates that women, when compared to men, exhibit greater IL-6 reactivity after exposure to laboratory-evoked pain. Such sex differences may explain the mechanisms underlying women's higher chronic pain risk and pain perception, as well as provide further insight in developing personalized pain interventions.

Altered mesocorticolimbic functional connectivity in chronic low back pain patients at rest and following sad mood induction.

Depressive symptoms are common among individuals with chronic pain. Previous work suggests that chronic pain patients have difficulty regulating emotional responses, which is a risk factor for the development of major depressive disorder (MDD). Function of the mesocorticolimbic system, a neural network associated with reward processing, contributes to emotion regulation. This network's dysfunction has been described in chronic pain and MDD research and potentially underlies the relationship among emotion dysregulation, chronic pain, and MDD development. Given that mood induction paradigms have been used to measure emotion regulation, the present study examined intrinsic mesocorticolimbic functional connectivity (FC) after induced sad mood in individuals with and without chronic low back pain (cLBP). Thirty-three MDD-free individuals (17 cLBP) underwent resting-state scanning before and after sad memory-evoked mood induction. A Group [cLBP, healthy control (HC)] x Mood (Neutral, Sadness) repeated measures ANCOVA was conducted on seed-based FC data using a mesolimbic a priori region of interest. Interaction effects were identified in the orbital frontal cortex and inferior frontal gyrus [F(2,29) = 21.07, pFDR < .05. hp2 = .5]. Whereas cLBP showed significantly greater FC between these two regions and the mesolimbic seed under neutral mood, FC among these regions increased in HC and decreased in cLBP under sad mood. Exploratory graph theory analyses further describe between-group differences in mesocorticolimbic network properties. Findings support previous literature describing mesocorticolimbic dysfunction in cLBP and demonstrate aberrant function in emotion regulation. Mesocorticolimbic dysfunction during emotion regulation might contribute to the development of certain depressive phenotypes in chronic pain patients.