Back morphology and walking patterns mean 13.8 years after surgery for lumbar disk herniation in adolescents.

Introduction: In many pain conditions, there is lingering pain despite healed tissue damage. Our previous study shows that individuals who underwent surgery for lumbar disk herniation (LDH) during adolescence have worse health, more pain, and increased disk degeneration mean 13 years after surgery compared with controls. It is unclear if walking patterns segregate surgically treated LDH adolescents and controls at mean 13-year follow-up. Objectives: Here, we analyzed the relationship between gait, back morphology and other health outcomes in a cohort of individuals treated surgically because of lumbar disk herniation compared with controls. Methods: We analyzed gait during a walking paradigm, back morphology at the site of surgery, and standardized health outcomes, among individuals who received surgery for LDH as adolescents, "cases" (n = 23), compared with "controls" (n = 23). Results: There were gait differences in head (P = 0.021) and trunk angle (P = 0.021) between cases and controls in a direction where cases exhibited a posture associated with sickness. The gait variance was explained by subjective pain and exercise habits rather than objective disk degeneration. Conclusion: Over a decade after surgery for LDH during adolescence, health among cases is worse compared with controls. The head and trunk angles differ between cases and controls, indicating that the residual pain lingers and may cause changes in movement patterns long after a painful episode in early life. Gait may be a useful target for understanding maintenance of pain and disability among individuals treated surgically for LDH during adolescence.

Lumbar degeneration and quality of life in patients with lumbar disc herniation: a case-control long-term follow-up study.

BACKGROUND AND PURPOSE: Adults treated surgically for lumbar disc herniation in adolescence have a higher degree of lumbar disc degeneration than controls. We aimed to establish whether the degree of lumbar degeneration differs at diagnosis or at follow-up between surgically and non-surgically treated individuals. METHODS: We identified individuals with a lumbar disc herniation in adolescence diagnosed with magnetic resonance imaging (MRI) and contacted them for follow-up MRI. Lumbar degeneration was assessed according to Pfirrmann, Modic, and total end plate score (TEP score). Patient-reported outcome measures at follow-up comprised the Oswestry Disability Index (ODI), EQ-5D-3-level version, 36-Item Short Form Health Survey (SF-36), and Visual Analogue Scale (VAS) for back and leg pain. Fisher's exact test, Mann-Whitney U tests, Wilcoxon tests, and logistic regression were used for statistical analysis. RESULTS: MRIs were available at diagnosis and after a mean of 11.9 years in 17 surgically treated individuals and 14 non-surgically treated individuals. Lumbar degeneration was similar at diagnosis (P = 0.2) and at follow-up, with the exception of higher TEP scores in surgically treated individuals at levels L4-L5 and L5-S1 at follow-up (P ≤ 0.03), but this difference did not remain after adjustment for age and sex (P ≥ 0.8). There were no significant differences in patient-reported outcome measures between the groups at follow-up (all P ≥ 0.2). CONCLUSION: Adolescents with a lumbar disc herniation have, irrespective of treatment, a similar degree of lumbar degeneration at the time of diagnosis, and similar lumbar degeneration and patient-reported outcomes at long-term follow-up.

Association between expectations and clinical outcomes in online v. face-to-face therapy - an individual participant data meta-analysis.

BACKGROUND: Online treatments are increasing in number and are currently available for a wide range of clinical problems. To date little is known about the role of treatment expectations and other placebo-like mechanisms in online settings compared to traditional face-to-face treatment. To address this knowledge gap, we analyzed individual participant data from randomized clinical trials that compared online and face-to-face psychological interventions. METHODS: MEDLINE (Ovid) and PsycINFO (Ovid) were last searched on 2 February 2021. Randomized clinical trials of therapist guided online v. face-to-face psychological interventions for psychiatric or somatic conditions using a randomized controlled design were included. Titles, abstracts, and full texts of studies were independently screened by multiple observers. The Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline was followed. Authors of the matching trials were contacted for individual participant data. Ratings from the Credibility and Expectancy Questionnaire and the primary outcome measure from each trial were used to estimate the association between expectation ratings and treatment outcomes in online v. face-to-face interventions, using a mixed-effects model. RESULTS: Of 7045 screened studies, 62 full-text articles were retrieved whereof six studies fulfilled the criteria and provided individual participant data (n = 491). Overall, CEQ ratings predicted clinical outcomes (ß = 0.27) at end of treatment with no moderating effect of treatment modality (online v. face-to-face). CONCLUSIONS: Online treatment appears to be equally susceptible to expectancy effects as face-to-face therapy. This furthers our understanding of the importance of placebo-like factors in online treatment and may aid the improvement of healthcare in online settings.

The Placebo Effect in Psychosis: Why It Matters and How to Measure It.

Psychosis is characterized by unusual percepts and beliefs in the form of hallucinations and delusions. Antipsychotic medication, the primary treatment for psychosis, is often ineffective and accompanied by severe side effects, but research has not identified an effective alternative in several decades. One reason that clinical trials fail is that patients with psychosis tend to show a significant therapeutic response to inert control treatments, known as the placebo effect, which makes it difficult to distinguish drug effects from placebo effects. Conversely, in clinical practice, a strong placebo effect may be useful because it could enhance the overall treatment response. Identifying factors that predict large placebo effects could improve the future outlook of psychosis treatment. Biomarkers of the placebo effect have already been suggested in pain and depression, but not in psychosis. Quantifying markers of the placebo effect would have the potential to predict placebo effects in psychosis clinical trials. Furthermore, the placebo effect and psychosis may represent a shared neurocognitive mechanism in which prior beliefs are weighted against new sensory information to make inferences about reality. Examining this overlap could reveal new insights into the mechanisms underlying psychosis and indicate novel treatment targets. We provide a narrative review of the importance of the placebo effect in psychosis and propose a novel method to assess it.

Anti-satellite glia cell IgG antibodies in fibromyalgia patients are related to symptom severity and to metabolite concentrations in thalamus and rostral anterior cingulate cortex.

Recent translational work has shown that fibromyalgia might be an autoimmune condition with pathogenic mechanisms mediated by a peripheral, pain-inducing action of immunoglobulin G (IgG) antibodies binding to satellite glia cells (SGC) in the dorsal root ganglia. A first clinical assessment of the postulated autoimmunity showed that fibromyalgia subjects (FMS) had elevated levels of antibodies against SGC (termed anti-SGC IgG) compared to healthy controls and that anti-SGC IgG were associated with a more severe disease status. The overarching aim of the current study was to determine whether the role of anti-SGC IgG in driving pain is exclusively through peripheral mechanisms, as indirectly shown so far, or could be attributed also to central mechanisms. To this end, we wanted to first confirm, in a larger cohort of FMS, the relation between anti-SGC IgG and pain-related clinical measures. Secondly, we explored the associations of these autoantibodies with brain metabolite concentrations (assessed via magnetic resonance spectroscopy, MRS) and pressure-evoked cerebral pain processing (assessed via functional magnetic resonance imaging, fMRI) in FMS. Proton MRS was performed in the thalamus and rostral anterior cingulate cortex (rACC) of FMS and concentrations of a wide spectrum of metabolites were assessed. During fMRI, FMS received individually calibrated painful pressure stimuli corresponding to low and high pain intensities. Our results confirmed a positive correlation between anti-SGC IgG and clinical measures assessing condition severity. Additionally, FMS with high anti-SGC IgG levels had higher pain intensity and a worse disease status than FMS with low anti-SGC IgG levels. Further, anti-SGC IgG levels negatively correlated with metabolites such as scyllo-inositol in thalamus and rACC as well as with total choline and macromolecule 12 in thalamus, thus linking anti-SGC IgG levels to the concentration of metabolites in the brain of FMS. However, anti-SGC IgG levels in FMS were not associated with the sensitivity to pressure pain or the cerebral processing of evoked pressure pain. Taken together, our results suggest that anti-SGC IgG might be clinically relevant for spontaneous, non-evoked pain. Our current and previous translational and clinical findings could provide a rationale to try new antibody-related treatments in FMS.

Conditioning induced placebo-like and nocebo-like effects of thermal discomfort in adults but not in youth.

Introduction: Conditioning can be used to modulate the perception of pain, in the form of placebo and nocebo effects. Previous studies show inconsistent results as to whether adolescents show similar, weaker, or non-significant conditioned placebo and nocebo effects compared to effects found in adults. There are suggestions that such differences (if any) may dependent on the cues used in the thermal conditioning paradigms. Therefore, in this current study, we utilized novel, neutral 3D-shaped visual cues to implicitly induce conditioned placebo-like and nocebo-like effects in adolescents and adults. Methods: During the conditioning paradigm, distinct cues (Fribbles) were paired with low and high temperatures in 24 adults and 20 adolescents (mean age = 25.5 years). In the testing phase, these conditioned cues as well as a neutral (unconditioned) cue were presented with moderate temperatures. Results: Thermal discomfort of moderate temperatures was lower when presented with the conditioned low heat cue (placebo-like effect) and higher when thermal stimuli were presented with the high heat cue (nocebo-like effect) compared to the neutral cue. The effects were driven by adults, as neither the placebo-like nor the nocebo-like effect was significant in adolescents. The difference between adolescents and adults was not explained by differences in temperature or discomfort levels, as adults and adolescents had comparable calibrated temperatures and levels of discomfort during heat stimuli. Conclusion: Our findings suggest that thermal perception in adolescents is less influenced by conditioning to an engaging novel visual cue, compared to adults. Our work may have implications for better understanding the scope and limitations of conditioning as a key mechanism of placebo and nocebo effects in youth.

Dysfunctional Activation of the Dorsolateral Prefrontal Cortex During Pain Anticipation Is Associated With Altered Subsequent Pain Experience in Fibromyalgia Patients.

The ability to accurately predict pain is an adaptive feature in healthy individuals. However, in chronic pain, this mechanism may be selectively impaired and can lead to increased anxiety and excessive avoidance behavior. Recently, we reported the first data demonstrating brain activation in fibromyalgia (FM) patients during conditioned pain responses, in which FM patients revealed a tendency to form new pain-related associations rather than extinguishing irrelevant ones. The aim of the present study was to extend our previous analysis, to elucidate potential neural divergences between subjects with FM (n = 65) and healthy controls (HCs) (n = 33) during anticipatory information (ie, prior to painful stimulus onset). Using functional magnetic resonance imaging (fMRI), the current analyses include 1) a congruently cued paradigm of low and high pain predictive cues, followed by 2) an incongruently cued paradigm where low and high pain predictive cues were followed by an identical mid-intensity painful pressure. During incongruently cued high-pain associations, FM exhibited reduced left dorsolateral prefrontal cortex (dlPFC) activation compared to HCs, which was followed by an altered subsequent pain experience in FM, as patients continued to rate the following painful stimuli as high, even though the pressure had been lowered. During congruently cued low pain anticipation, FM exhibited decreased right dlPFC activation compared to HCs, as well as decreased brain connectivity between brain regions implicated in cognitive modulation of pain (dlPFC) and nociceptive processing (primary somatosensory cortex/postcentral gyrus [S1] and supplementary motor area [SMA]/midcingulate cortex [MCC]). These results may reflect an important feature of validating low pain expectations in HCs and help elucidate behavioral reports of impaired safety processing in FM patients. PERSPECTIVE: FM exhibited a stronger conditioned pain response for high-pain associations, which was associated with reduced dlPFC activation during the incongruent trial. During (congruent and incongruent) low pain associations, FM dlPFC brain activation remained indifferent. Imbalances in threat and safety pain perception may be an important target for psychotherapeutic interventions.

Undergraduate student perceptions of stress and mental health in engineering culture.

Background: Mental health for engineering undergraduates is an urgent topic for engineering educators. Narratives of engineering education requiring suffering may create or exacerbate problematic perceptions around stress and mental health in engineering. This study explored the roles of stress and mental health in engineering culture. We sought to explore: (1) how engineering students describe their experiences related to stress and mental health and (2) norms and expectations engineering students share about stress and mental health. Qualitative interview data were collected from 30 students who had previously responded to a college-wide survey. Results: Codes related to experiences with stress and mental health in engineering were organized in a bioecological systems model and analyzed for emergent themes depicting engineering culture. The study identified three themes related to stress and mental health in engineering culture: (1) engineering workload as a defining stressor, (2) specific barriers that prevent engineering students from seeking help for mental health concerns, and (3) reliance on peers to cope with stress and mental health distress. Conclusions: Our analysis provided insight into how engineering students perceive norms around stress and mental health in engineering and how this impacts help-seeking for mental health challenges. These findings have important implications for developing interventions and positive cultures that support student mental health.

Susceptibility to Nocebo Hyperalgesia, Dispositional Optimism, and Trait Anxiety as Predictors of Nocebo Hyperalgesia Reduction.

OBJECTIVES: The current paper explores the psychological predictors of nocebo hyperalgesia and whether the reduction of nocebo hyperalgesia can be predicted by susceptibility to nocebo hyperalgesia and psychological characteristics. METHODS: Nocebo effects on pressure pain were first experimentally induced in 83 healthy female participants through conditioning with open-label instructions about the pain-worsening function of a sham TENS device to assess susceptibility to nocebo hyperalgesia. Participants were then randomized to 1 out of 2 nocebo-reduction conditions (counterconditioning/extinction) or to continued nocebo-conditioning (control), each combined with open-label instructions about the new sham device function. Dispositional optimism, trait and state anxiety, pain catastrophizing, fear of pain, and body vigilance were assessed at baseline. RESULTS: The results showed that lower optimism and higher trait anxiety were related to a stronger induction of nocebo hyperalgesia. Moreover, a stronger induction of nocebo hyperalgesia and higher trait anxiety predicted a larger nocebo reduction across interventions. Also, nocebo hyperalgesia and optimism moderated the effects of the nocebo-reduction interventions, whereby larger nocebo hyperalgesia and lower optimism were associated with a larger nocebo reduction after counterconditioning, compared with control, and also extinction for larger nocebo hyperalgesia. DISCUSSION: Our findings suggest that open-label conditioning leads to stronger nocebo hyperalgesia when trait anxiety is high and dispositional optimism is low, while these psychological characteristics, along with larger nocebo hyperalgesia, also predict open-label counterconditioning to be an effective nocebo-reduction strategy. Susceptibility to nocebo hyperalgesia, trait anxiety, and dispositional optimism might be indicators of a flexible pain regulatory system.

Efficacy of open-label counterconditioning for reducing nocebo effects on pressure pain.

BACKGROUND: Nocebo effects can adversely affect the experience of physical symptoms, such as pain and itch. Nocebo effects on itch and pain have shown to be induced by conditioning with thermal heat stimuli and reduced by counterconditioning. However, open-label counterconditioning, in which participants are informed about the placebo content of the treatment, has not been investigated, while this can be highly relevant for clinical practice. Furthermore, (open-label) conditioning and counterconditioning has not been investigated for pain modalities relevant to musculoskeletal disorders, such as pressure pain. METHODS: In a randomized controlled trial, we investigated in 110 healthy female participants whether nocebo effects on pressure pain combined with open-label verbal suggestions can be (1) induced via conditioning and (2) reduced via counterconditioning. Participants were allocated to either a nocebo- or sham-conditioning group. Next, the nocebo group was allocated to either counterconditioning, extinction or continued nocebo conditioning; sham conditioning was followed by placebo conditioning. RESULTS: Nocebo effects were significantly larger after nocebo conditioning than sham conditioning (d = 1.27). Subsequently, a larger reduction of the nocebo effect was found after counterconditioning than after extinction (d = 1.02) and continued nocebo conditioning (d = 1.66), with effects similar to placebo conditioning (following sham conditioning). CONCLUSIONS: These results show that (counter)conditioning combined with open-label suggestions can modulate nocebo effects on pressure pain, which provides promise in designing learning-based treatments to reduce nocebo effects in patients with chronic pain disorders, particularly for musculoskeletal disorders. SIGNIFICANCE: Few studies have investigated the efficacy counterconditioning to reduce nocebo effects. Whereas typically deceptive procedures are used, these are not ethically appropriate for use in clinical practice. The current study demonstrates that open-label counterconditioning in a pain modality relevant for many chronic pain conditions may be a promising new strategy for reducing nocebo effects in a non-deceptive and ethical manner, which provides promise in designing learning-based treatments to reduce nocebo effects in patients with chronic pain disorders.

Placebo effects in children with autism spectrum disorder.

Placebo responses are frequently observed in research studies and clinical contexts, yet there is limited knowledge about the placebo effect among children with neurodevelopmental disorders. Here, we review the placebo effect in autism spectrum disorder (ASD). Placebo responses are widely evident in ASD clinical trials and could partly operate via so-called placebo-by-proxy, whereby caregivers or clinicians indirectly shape patient outcomes. Understanding the role of placebo effects in ASD may help discern genuine treatment effects from contextual factors in clinical trials. The much less studied nocebo effect, or negative placebo, might contribute to the experience of side effects in ASD treatments but empirical data is missing. Better knowledge about placebo and nocebo mechanisms may contribute to the development of more effective research designs, such as three-armed designs that account for natural history, and improved treatments for ASD symptoms. At a clinical level, deeper knowledge about placebo and nocebo effects may optimize the delivery of care for individuals with ASD in the future. WHAT THIS PAPER ADDS: Placebo responses are evident in autism spectrum disorder (ASD) clinical trials. Placebo responses in ASD are likely dependent on a placebo-by-proxy mechanism.

Efficacy of mecobalamin (vitamin B12) in the treatment of long-term pain in women diagnosed with fibromyalgia: protocol for a randomised, placebo-controlled trial.

INTRODUCTION: Fibromyalgia causes long-term pain. It affects at least 2% of the population, the majority being women. In addition, extended symptoms corresponding to vitamin B12 deficiency occur. Findings from several studies have indicated that vitamin B12 may be a possible treatment for pain in fibromyalgia. The aim of the proposed study is to evaluate whether vitamin B12 decreases pain sensitivity and the experience of pain (ie, hyperalgesia and allodynia) in women with fibromyalgia. METHODS AND ANALYSIS: The study is a randomised, placebo-controlled, single-blind, clinical trial with two parallel groups which are administered mecobalamin (vitamin B12) or placebo over 12 weeks. 40 Swedish women aged 20-70 years with an earlier recorded diagnosis of fibromyalgia are randomised into the placebo group or the treatment group, each consisting of 20 participants. Outcomes consist of questionnaires measured at baseline and after 12 weeks of treatment. A final re-evaluation will then follow 12 weeks after treatment ends. The primary outcome is tolerance time, maximised to 3 min, which is assessed using the cold pressor test. In order to broaden the understanding of the lived experience of participants, qualitative interviews will be conducted using a phenomenological approach on a lifeworld theoretical basis (reflective lifeworld research approach). ETHICS AND DISSEMINATION: The protocol for the study is approved by the local ethical committee at Linkoping (EPM; 2018/294-31, appendices 2019-00347 and 2020-04482). The principles of the Helsinki Declaration are followed regarding oral and written consent to participate, confidentiality and the possibility to withdraw participation from the study at any time. The results will primarily be communicated through peer-reviewed journals and conferences. TRIAL REGISTRATION NUMBER: NCT05008042.

LabMate: Development and Implementation of a Novel Livestreaming Platform for Hybrid or Remote Laboratory Course Delivery.

Online course delivery has increased in prevalence, particularly due to the onset in 2020 of the COVID-19 pandemic. Biomedical engineering laboratory courses pose unique challenges when transitioning to a remote or hybrid space. Here, we describe a novel approach to online lab delivery to improve student learning and engagement in a required introductory biomedical engineering laboratory class. The presented work focuses on the implementation and assessment of a novel approach to remote lab delivery named LabMate, which is a mobile, multi-view livestreaming platform that connects students to an in-person class remotely. Surveys of student and instructor participants assessed hardware quality and areas of improvement. Focus groups with students who had taken the course in an online format previously were conducted after a demonstration of the system. Survey responses were overall positive; however, some areas of improvement were identified, such as audio quality and video quality. Students and instructors appreciated the ability to deliver class synchronously online rather than perform make-up labs. Focus group participants found LabMate to be more engaging and enjoyable than prior online lab experiences. Students and instructors preferred LabMate over other online lab delivery methods. The students found the experience to be more dynamic and engaging, providing them with the opportunity to develop some of the core competencies of a biomedical engineering student.

Placebo Response and Media Attention in Randomized Clinical Trials Assessing Cannabis-Based Therapies for Pain: A Systematic Review and Meta-analysis.

Importance: Persistent pain is a common and disabling health problem that is often difficult to treat. There is an increasing interest in medicinal cannabis for treatment of persistent pain; however, the limited superiority of cannabinoids over placebo in clinical trials suggests that positive expectations may contribute to the improvements. Objective: To evaluate the size of placebo responses in randomized clinical trials in which cannabinoids were compared with placebo in the treatment of pain and to correlate these responses to objective estimates of media attention. Data Sources: A systematic literature search was conducted within the MEDLINE and Embase databases. Studies published until September 2021 were considered. Study Selection: Cannabinoid studies with a double-blind, placebo-controlled design with participants 18 years or older with clinical pain of any duration were included. Studies were excluded if they treated individuals with HIV/AIDS or severe skin disorders. Data Extraction and Synthesis: The study followed the Preferred Reporting Items for Systematic Review and Meta-analyses reporting guideline. Data were extracted by independent reviewers. Quality assessment was performed using the Risk of Bias 2 tool. Attention and dissemination metrics for each trial were extracted from Altmetric and Crossref. Data were pooled and analyzed using a random-effects statistical model. Main Outcomes and Measures: Change in pain intensity from before to after treatment, measured as bias-corrected standardized mean difference (Hedges g). Results: Twenty studies, including 1459 individuals (mean [SD] age, 51 [7] years; age range, 33-62 years; 815 female [56%]), were included. Pain intensity was associated with a significant reduction in response to placebo, with a moderate to large effect size (mean [SE] Hedges g, 0.64 [0.13]; P < .001). Trials with low risk of bias had greater placebo responses (q1 = 5.47; I2 = 87.08; P = .02). The amount of media attention and dissemination linked to each trial was proportionally high, with a strong positive bias, but was not associated with the clinical outcomes. Conclusions and Relevance: Placebo contributes significantly to pain reduction seen in cannabinoid clinical trials. The positive media attention and wide dissemination may uphold high expectations and shape placebo responses in future trials, which has the potential to affect the outcome of clinical trials, regulatory decisions, clinical practice, and ultimately patient access to cannabinoids for pain relief.

Parental responses and catastrophizing in online cognitive behavioral therapy for pediatric functional abdominal pain: A mediation analysis of a randomized controlled trial.

Objective: To test if decreased parental protective behaviors, monitoring behaviors, and parental catastrophizing mediate relief of gastrointestinal symptoms in children 8-12 years with functional abdominal pain disorders (FAPDs). The study uses secondary data analyses of a randomized controlled trial in which exposure-based online cognitive behavioral therapy (ICBT) was found superior to treatment as usual in decreasing gastrointestinal symptoms. Methods: The ICBT included 10 weekly modules for children and 10 weekly modules for parents. Treatment as usual consisted of any medication, dietary adjustments, and healthcare visits that the participants engaged in during 10 weeks. All measures were self-assessed online by parents. Biweekly assessments of the Adult Responses to Children's Symptoms (ARCS), Protect and Monitor subscales, and the Pain Catastrophizing Scale, parental version (PCS-P) were included in univariate and multivariate growth models to test their mediating effect on the child's gastrointestinal symptoms assessed with the Pediatric Quality of Life Gastrointestinal Symptoms Scale (PedsQL). Results: A total of 90 dyads of children with FAPDs and their parents were included in the study, of which 46 were randomized to ICBT and 44 to treatment as usual. The PCS-P was found to mediate change in the PedsQL ab = 0.639 (95% CI 0.020-2.331), while the ARCS Monitor ab = 0.472 (95% CI -1.002 to 2.547), and Protect ab = -0.151 (95% CI -1.455 to 0.674) were not mediators of change. Conclusions: To target parental catastrophizing in ICBT for pediatric FAPDs is potentially important to reduce abdominal symptoms in children.

Augmented pain inhibition and higher integration of pain modulatory brain networks in women with self-injury behavior.

Individuals who engage in nonsuicidal self-injury (NSSI) have demonstrated insensitivity to pain compared with individuals without NSSI. Yet, the neural mechanisms behind this difference are unknown. The objective of the present study was to determine which aspects of the pain regulatory system that account for this decreased sensitivity to pain. In a case-control design, 81 women, aged 18-35 (mean [SD] age, 23.4 [3.9]), were included (41 with NSSI and 40 healthy controls). A quantitative sensory testing protocol, including heat pain thresholds, heat pain tolerance, pressure pain thresholds, conditioned pain modulation (assessing central down-regulation of pain), and temporal summation (assessing facilitation of pain signals) was used. Pain-evoked brain responses were assessed by means of fMRI scanning during thermal pain. NSSI participants showed a more effective central down-regulation of pain, compared to controls, assessed with conditioned pain modulation. The neural responses to painful stimulation revealed a stronger relation between nociceptive and pain modulatory brain regions in NSSI compared to controls. In line with previous studies, pressure and heat pain thresholds were higher in participants with NSSI, however, there were no correlations between pain outcomes and NSSI clinical characteristics. The augmented pain inhibition and higher involvement of pain modulatory brain networks in NSSI may represent a pain insensitive endophenotype associated with a greater risk for developing self-injurious behavior.

Development and Implementation of a Remote Enzyme Kinetics Laboratory Exercise.

The COVID-19 pandemic imposed many new challenges on educational systems and increased the demand for novel strategies for effectively teaching laboratory skills without in-person instruction and without access to laboratory space, including critical specialized equipment. While this novel remote instruction modality is compatible with teaching the theory behind experimental techniques, the lack of lab activities that enable learning of laboratory skills severely limits the outcome of instruction. In order to overcome this problem and effectively supplement lectures with hands-on laboratory exercises, we developed an at-home enzyme kinetics lab that provides a safe alternative to traditional enzyme kinetics instructional labs typically performed in a laboratory setting. The combination of a simple design of the activity, accessibility of equipment used, and relatively low overall cost yields an effective exercise for teaching experimental design and basic laboratory skills remotely while providing a unique opportunity for students to learn about enzyme kinetics.

Placebo and nocebo effects in youth: subjective thermal discomfort can be modulated by a conditioning paradigm utilizing mental states of low and high self-efficacy.

INTRODUCTION: Conditioning is a key mechanism of placebo and nocebo effects in adults, but little is known about these effects in youth. This study investigated whether personalized verbal cues evoking a sense of high or low self-efficacy can induce conditioned placebo and nocebo effects on subjective discomfort of noxious heat in youth. METHODS: In a structured interview, 26 adolescents (13-18 years) described personal situations in which they experienced a sense of high, low or neutral self-efficacy. Participants were then asked to recall these memories during a conditioning paradigm, in which a high thermal stimulus applied to the forearm was repeatedly paired with a low self-efficacy cue and a low thermal stimulus with a high self-efficacy cue. In a testing phase, high, low and neutral self-efficacy cues were paired with the same moderate temperature. We hypothesized that conditioned high and low self-efficacy cues would induce conditioned placebo and nocebo responses to moderate temperatures. RESULTS: Moderate temperatures were rated as more uncomfortable when paired with the conditioned low compared with the neutral self-efficacy cue (nocebo effect). While in the whole-group analysis, there was no significant difference between ratings of moderate thermal stimuli paired with high compared with neutral self-efficacy cues (placebo effect), a sub-group of participants with a greater range of emotional valence between high and neutral self-efficacy cues revealed a significant placebo effect. The strength of the nocebo effect was associated with higher anxiety and lower hope. CONCLUSION: Conditioned associations using internal self-efficacy states can change subjective discomfort of thermal sensations.

Brain network segregation and integration during painful thermal stimulation.

The present study aimed to determine changes in brain network integration/segregation during thermal pain using methods optimized for network connectivity events with high temporal resolution. Participants (n = 33) actively judged whether thermal stimuli applied to the volar forearm were painful or not and then rated the warmth/pain intensity after each trial. We show that the temporal evolution of integration/segregation within trials correlates with the subjective ratings of pain. Specifically, the brain shifts from a segregated state to an integrated state when processing painful stimuli. The association with subjective pain ratings occurred at different time points for all networks. However, the degree of association between ratings and integration/segregation vanished for several brain networks when time-varying functional connectivity was measured at lower temporal resolution. Moreover, the increased integration associated with pain is explained to some degree by relative increases in between-network connectivity. Our results highlight the importance of investigating the relationship between pain and brain network connectivity at a single time point scale, since commonly used temporal aggregations of connectivity data may result in that fine-scale changes in network connectivity may go unnoticed. The interplay between integration/segregation reflects shifting demands of information processing between brain networks and this adaptation occurs both for cognitive tasks and nociceptive processing.