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Diagnostic uncertainty in pediatric chronic pain: nature, prevalence, and consequences.

Diagnostic uncertainty (DU), which is the perception that a label or explanation for a patient's health problem is missing or inaccurate, has been linked to distress, anxiety, and difficulty coping among adults with pain. This study examined the prevalence of DU among youth with chronic pain and their parents and the relation of parent and youth DU with youth pain, pain-related constructs, and health-related quality of life (HRQoL).

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A Phenomenological Exploration of the Personal Implications of Female Adolescents Living With Chronic Pain.

Chronic pain (CP) negatively impacts everyday previously taken-for-granted activities resulting in considerable psychosocial stress for the individual. Qualitative research in pediatric CP is limited despite the considerable influence CP has on the process of establishing one's personal identity during these formative years and invites the opportunity to understand how CP affects these young individuals from their perspective. The objective of the study was to inquire into the experiences of female adolescents living with CP in order to enhance our understanding of how CP affects their personal lives.

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Conditioning open-label placebo: a pilot pharmacobehavioral approach for opioid dose reduction and pain control.

Opioid consumption for those in comprehensive inpatient rehabilitation units is high because of the complexity of their injuries. Notably, pain in rehabilitation leads to worsened clinical outcomes because of maladaptive behaviors and poor engagement during therapies. It is critical to developing evidence-based pharmacobehavioral interventions. Based on principles of classical conditioning, conditioning open-label placebo (COLP) is a promising approach for reducing opioid use in comprehensive inpatient rehabilitation, and this technique takes advantage of the possibility of association learning and opioid pharmacology to promote evoked placebo-driven analgesia.

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Naltrexone during pain conditioning: A double-blind placebo-controlled experimental trial.

Naltrexone reversibly blocks the effects of opioids and has been shown to decrease placebo analgesia. However, it is not clear (1) to what extent naltrexone affects pain modulation in a nontreatment context, for example, in response to pain cues or (2) how naltrexone given prior to pain-cue learning shapes pain responses. In a double-blind procedure prior to pain-cue conditioning, 30 healthy participants were randomized to receive an oral dose of naltrexone (50 mg) or inert pill. During functional magnetic resonance imaging, high and low pain pressures were paired with two different visual cues: a high pain cue and a low pain cue (learning sequence). During a test sequence, medium levels of pressure were used for both cues and the difference in subjective pain ratings following high and low pain cues was calculated. Results showed significant conditioned pain responses across groups (<.001); however, no significant difference between participants receiving naltrexone or inert pill (=.193). There was a significant correlation between the difference in high and low pain ratings during the learning sequence and the effect of high and low pain cues during the test sequence (r = .575, =.002). Functional magnetic resonance imaging analyses revealed no significant difference in brain activation between groups. Here, we demonstrate comparable learning of pain responses in participants treated with naltrexone or inert pill. The results point to the possibility that associative learning, and conditional responding to pain cues, is not dependent on endogenous opioids. Our results, using pain-cue conditioning to create reduced pain responses, contrast previous studies where opioid antagonists significantly reduced the placebo effect in treatment of pain.

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Resilience factors may buffer cellular aging in individuals with and without chronic knee pain.

Telomere length, a measure of cellular aging, is inversely associated with chronic pain severity. While psychological resilience factors (e.g., optimism, acceptance, positive affect, active coping) are associated with lower levels of clinical pain and greater physical functioning, it is unknown whether resilience may buffer against telomere shortening in individuals with chronic pain. Additionally, a broader conceptualization of resilience that includes social and biobehavioral factors may improve our understanding of the relationship between resilience, chronic pain, and health outcomes. In individuals with and without chronic knee pain, we investigated whether: 1) psychological resilience would be positively associated with telomere length, and if 2) a broader conceptualization of resilience including social and biobehavioral factors would strengthen the association. Seventy-nine adults, 45-85 years of age, with and without knee pain completed demographic, health, clinical pain, psychological, social, and biobehavioral questionnaires. Resilience levels were determining by summing the total number of measures indicating resilience based on published clinical ranges and norms. Blood samples were collected and telomere length determined. In regression analyses controlling for sex, race, age, and characteristic pain intensity, greater psychological resilience and psychosocial/biobehavioral resilience were associated with longer telomeres (p = .0295 and p = .0116, respectively). When compared, psychosocial/biobehavioral resilience was significantly more predictive of telomere length than the psychological resilience (p < .0001). Findings are promising and encourage further investigations to enhance understanding of the biological interface of psychosocial and biobehavioral resilience factors in individuals with musculoskeletal chronic pain conditions.

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Understanding Links among Opioid Use, Overdose, and Suicide.

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Moderators of mindfulness meditation, cognitive therapy, and mindfulness-based cognitive therapy for chronic low back pain: A test of the Limit, Activate and Enhance model.

This study examined psychosocial pain treatment moderation in a secondary analysis of a trial that compared cognitive therapy (CT), mindfulness-meditation (MM), and mindfulness-based cognitive therapy (MBCT) for chronic low back pain (CLBP). The Limit, Activate and Enhance (LA&E) model of moderation provided a framework for testing a priori hypotheses. Adult participants (N=69) with CLBP completed a pre-treatment assessment of hypothesized moderators: pain catastrophizing, brain state as assessed by electroencephalogram, mindful observing, and non-reactivity. Outcomes were pain interference, characteristic pain intensity, physical function, and depression, assessed at pre- and post-treatment. Moderation analyses found significant interaction effects, specifically: (1) higher and lower baseline pain catastrophizing was associated with greater improvement in pain intensity in MM and MBCT, respectively; (2) higher baseline theta power was associated with greater improvement in depression in MBCT and interfered with response to CT; (3) lower baseline non-reactivity was associated with greater improvement in physical function in MM while higher non-reactivity was associated with greater improvement in MBCT. The findings support the possibility that different patients are more or less likely to benefit from various treatments. Theory-driven moderation research has the capacity to inform the development of patient-treatment matching algorithms to optimize outcome. Perspective: This study presents preliminary findings from theory-driven tests of the moderators of mindfulness meditation, cognitive therapy and mindfulness-based cognitive therapy for chronic low back pain. The results of such analyses may inform the understanding of for whom various evidence-based psychosocial pain treatments may engender the most meaningful benefits.

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Injustice Appraisal but not Pain Catastrophizing Mediates the Relationship Between Perceived Ethnic Discrimination and Depression and Disability in Low Back Pain.

Despite growing evidence of significant racial disparities in the experience and treatment of chronic pain, the mechanisms by which these disparities manifest have remained relatively understudied. The current study examined the relationship between past experiences of racial discrimination and pain-related outcomes (self-rated disability and depressive symptomatology), and tested the potential mediating roles of pain catastrophizing and perceived injustice related to pain. Analyses consisted of cross-sectional path modeling in a multiracial sample of 137 individuals with chronic low back pain (Hispanics N=43; Blacks N=43; Whites N=51). Results indicated a positive relationship between prior discriminatory experiences and severity of disability and depressive symptoms. In mediation analyses, pain-related appraisals of injustice, but not pain catastrophizing, were found to mediate these relationships. Notably, the association between discrimination history and perceived injustice was significantly stronger in Black and Hispanic participants and was not statistically significant in White participants. The findings suggest that race-based discriminatory experiences may contribute to racial disparities in pain outcomes and highlight the specificity of pain-related, injustice-related appraisals as a mechanism by which these experiences may impair physical and psychosocial function. Future research is needed to investigate temporal and causal mechanisms suggested by the model through longitudinal and clinical intervention studies. PERSPECTIVE: More frequent prior experiences of racial discrimination are associated with greater depressive symptomatology and pain-related disability in individuals with chronic low back pain. These associations are explained by the degree of injustice perception related to pain, but not pain catastrophizing, and were stronger among Black and Hispanic participants.

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Effects of oxytocin on placebo and nocebo effects in a pain conditioning paradigm: a randomized controlled trial.

Oxytocin has been shown to increase trust, decrease anxiety and affect learning as has been observed in conditioning paradigms. Trust, anxiety and learning are important factors that influence placebo effects. In this study we investigated whether oxytocin can increase placebo analgesia, decrease nocebo hyperalgesia, and influence extinction processes of both. Eighty male volunteers were assigned to a 40 IU of oxytocin nasal spray group, or to a placebo control group. Placebo analgesia and nocebo hyperalgesia were induced by a conditioning procedure in combination with verbal suggestions. The results demonstrate that the conditioning procedure successfully elicited significant placebo analgesia and nocebo hyperalgesia responses (p < .001). Furthermore, extinction was observed (p < .001), although placebo and nocebo responses did not return to baseline and remained significant. Oxytocin did not influence placebo analgesia or nocebo hyperalgesia and had no effect on extinction. This study provides support against the placebo-boosting effects of oxytocin and was the first one to demonstrate that it also did not influence nocebo effects or extinction processes, however, these results pertain to only a male sample. As managing placebo and nocebo effects has widespread clinical implications, further research should investigate other neurobiological or behavioral pathways to boost placebo and decrease nocebo effects. Trial registration: The study protocol was preregistered on the website www.trialregister.nl under the number NTR6506. Perspective: The present study demonstrated that placebo analgesia and nocebo hyperalgesia can be successfully induced by conditioning and verbal suggestions. We could not confirm the hypothesis that oxytocin affects either of these phenomena. Other pharmacological agents and behavioral manipulations for increasing placebo and decreasing nocebo effects should be investigated.

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Brain mechanisms impacted by psychological therapies for pain: identifying targets for optimization of treatment effects.

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