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Conditioned Pain Modulation Efficiency is Associated with Pain Catastrophizing in Patients with Chronic Low Back Pain.

Previous studies have found a negative association between a conditioning pain modulating (CPM) response and pain catastrophizing among pain-free subjects. This study investigated the difference in CPM response between patients with chronic low back pain (CLBP) and healthy controls, and the association between pain catastrophizing and the CPM response.

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Association between chronic pain and long-term cognitive decline in a population-based cohort of elderly participants.

Chronic pain (CP) was associated with impaired cognitive performance in several cross-sectional studies conducted in older adults; however, fewer longitudinal studies assessed this link which remains still debated. With a prospective design, the present analysis was aimed at evaluating the relationship between CP and the change in several tests assessing memory, attention, verbal fluency and processing speed. The study population was selected from the PAQUID study, a cohort of community dwellers aged 65 and over; 693 subjects receiving a pain assessment were included. CP was evaluated using a questionnaire administered at 3-year follow-up. Cognitive performances were assessed every 2-3 years between 3 and 15 years assessing general cognition (MMSE), verbal and visual memory (word paired associate test and Benton test) attention and speed processing (Wechsler DSST, Zazzo's cancellation task) language skills and executive functions (Isaacs set test). The link between CP and the change in cognitive function was assessed with latent process mixed models controlled for age, gender, education, comorbidities, depression and analgesic drugs. The association between CP and each of the cognitive scores was then tested with the same procedure. A significant relationship was observed between CP and poorer 15-year scores on global cognitive performance (p=0.004), and specifically DSST (p=0.002) associated with a higher slope of decline (p=0.02). CP is associated with higher cognitive decline, in particular in processing speed. This result reinforces the importance of actively treating CP with pharmacological and non-pharmacological strategies to prevent its consequences, including cognitive consequences.

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Effects of sex on placebo effects in chronic pain participants: a cross-sectional study.

Sex-related differences can influence outcomes of randomized clinical trials and may jeopardize the effectiveness of pain management and other therapeutics. Thus, it is essential to understand the mechanistic and translational aspects of sex differences in placebo outcomes. Recently, studies in healthy participants have shed light on how sex-related placebo effects might influence outcomes, yet no research has been conducted in a patient population. Herein, we used a tripartite approach to evaluate the interaction of prior therapeutic experience (e.g. conditioning), expectations, and placebo effects in 280 chronic (orofacial) pain patients (215 women). In this cross-sectional study, we assessed sex differences in placebo effects, conditioning as a proxy of prior therapeutic effects, and expectations evaluated before and after the exposure to positive outcomes, taking into account participant-experiment sex concordance and hormonal levels (estradiol and progesterone assessed in premenopausal women). We used mediation analysis to determine how conditioning strength and expectations impacted sex differences in placebo outcomes. Independent of gonadal hormone levels, women showed stronger placebo effects than men. We also found significant statistical sex differences in the conditioning strength and reinforced expectations whereby reinforced expectations mediated the sex-related placebo effects. Additionally, the participant-experimenter sex concordance influenced conditioning strength, reinforced expectations, and placebo effects in women but not in men. Our findings suggest that women experience larger conditioning effects, expectations and placebo response emphasizing the need to consider sex as a biological variable when placebo outcomes are parts of drug development trials and in pain management.

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The prevalence and predictors of burnout symptoms in multidisciplinary pain clinics: a mixed-methods study.

Frequent exposure to patient distress is associated with higher prevalence of clinician distress and symptoms of burnout. Patients with chronic pain often present with high levels of emotional distress. The current study examined the prevalence of burnout symptoms among a multidisciplinary sample of pain clinicians in Australia, the relationship between clinician confidence managing emotions and symptoms of burnout, and clinicians' perspectives on sources of stress and wellbeing at work. One hundred and seventy-six clinicians from 58 multidisciplinary pain clinics across Australia completed a survey including the 22-item Maslach Burnout Inventory, a measure of clinician confidence managing patient emotions and their own emotions, and open-ended questions probing clinician perspectives on sources of stress and wellbeing at work. High levels of emotional exhaustion and depersonalisation were reported by 21.6% and 14.2% of respondents, respectively. These burnout symptoms were predicted by clinician confidence managing their own emotions. Low levels of personal accomplishment were reported by 18.8% of respondents and were predicted by clinician confidence managing patients' emotions. Consistent with these quantitative findings, qualitative data revealed that emotionally challenging patient encounters were common sources of stress. Working with a multidisciplinary team and supportive relationships with colleagues were commonly reported sources of clinician wellbeing. The results of this study are discussed in light of previous reports of burnout in pain medicine physicians. Implications for clinician training in pain management and the prevention of burnout in pain clinicians are discussed.

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Hyporesponsivity to mu-opioid receptor agonism in the Wistar-Kyoto rat model of altered nociceptive responding associated with negative affective state.

Chronic pain is often comorbid with anxiety and depression, altering the level of perceived pain, which negatively affects therapeutic outcomes. The role of the endogenous mu-opioid receptor (MOP) system in pain-negative affect interactions and the influence of genetic background thereon is poorly understood. The inbred Wistar-Kyoto (WKY) rat, which mimics aspects of anxiety and depression, displays increased sensitivity (hyperalgesia) to noxious stimuli, compared to Sprague-Dawley (SD) rats. Here, we report that WKY rats are hyporesponsive to the antinociceptive effects of systemically administered MOP agonist morphine in the hot plate and formalin tests, compared to SD counterparts. Equivalent plasma morphine levels in the two rat strains suggested that these differences in morphine sensitivity were unlikely to be due to strain-related differences in morphine pharmacokinetics. Although MOP expression in the ventrolateral periaqueductal grey (vlPAG) did not differ between WKY and SD rats, the vlPAG was identified as a key locus for the hyporesponsivity to MOP agonism in WKY rats in the formalin test. Moreover, morphine-induced effects on c-Fos (a marker of neuronal activity) in regions downstream of vlPAG, namely the rostral ventromedial medulla and lumbar spinal dorsal horn, were blunted in the WKY rats. Together, these findings suggest that a deficit in MOP-induced recruitment of the descending inhibitory pain pathway may underlie hyperalgesia to noxious inflammatory pain in the WKY rat strain genetically predisposed to negative affect.

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Neurophysiological Mechanisms Supporting Mindfulness Meditation-Based Pain Relief: an Updated Review.

This review examines recent (2016 onwards) neuroscientific findings on the mechanisms supporting mindfulness-associated pain relief. To date, its clear that mindfulness lowers pain by engaging brain processes that are distinct from placebo and vary across meditative training level. Due to rapid developments in the field of contemplative neuroscience, an update review on the neuroimaging studies focused on mindfulness, and pain is merited.

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Low back pain and the social determinants of health: a systematic review and narrative synthesis.

The social determinants of health (SDH) are known to differentially impact outcomes from many noncommunicable diseases; however, their potential role in low back pain (LBP) is poorly defined. This review endeavours to comprehensively inform the field of their relevance. Our research question was: "How do the broad range of SDH and chronic LBP (CLBP) relate?" The primary aim of this review was to synthesise evidence of relationships between SDH and the frequency or severity of CLBP. Secondary aims were to identify relationships between SDH and LBP-related disability, work absenteeism, and opioid prescription. We included studies involving adult participants that evaluated relationships between one or more of the SDH and CLBP frequency or LBP outcomes (beyond 3 months). Two reviewers screened studies, extracted data, and assessed risk of bias. We synthesized the results narratively and applied PROGRESS to organise our findings. Database searches identified 7018 records. Forty-one studies were included, containing data from 2,161,617 adults from 17 countries. Twenty-four percent and 19% of the relationships included were classified as having a high risk of bias due to confounding and missing data, respectively. We reported 166 relationships representing the majority of the PROGRESS domains. An array of independent and interdependent relationships between the SDH and CLBP were identified with the strongest evidence for associations related to educational attainment and socioeconomic status. Our findings suggest that greater recognition of the contribution of SDH to disparities in LBP outcomes is warranted and this has the potential to usefully inform strategies to impact burden.

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Decomposing conditioned avoidance performance with computational models.

Avoidance towards innocuous stimuli is a key characteristic across anxiety-related disorders and chronic pain. Insights into the relevant learning processes of avoidance are often gained via laboratory procedures, where individuals learn to avoid stimuli or movements that have been previously associated with an aversive stimulus. Typically, statistical analyses of data gathered with conditioned avoidance procedures include frequency data, for example, the number of times a participant has avoided an aversive stimulus. Here, we argue that further insights into the underlying processes of avoidance behavior could be unraveled using computational models of behavior. We then demonstrate how computational models could be used by reanalysing a previously published avoidance data set and interpreting the key findings. We conclude our article by listing some challenges in the direct application of computational modeling to avoidance data sets.

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Prevalence of suicidal ideation and suicide attempt in patients with migraine: A systematic review and meta-analysis.

Suicidality is common in patients with migraine. Here, we performed a systematic review and estimated the prevalence of suicidal ideation (SI) and suicide attempt (SA) in patients with migraine.

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Feasibility and acceptability of a single-session, videoconference-delivered group intervention for pain in multiple sclerosis.

Chronic pain is one of the most common and interfering symptoms experienced by people with MS. There is an opportunity to shift the paradigm from interventions delivered after pain has become chronic to early, proactive interventions to alter the impact of MS-related pain. The purpose of this study was to develop and test a remotely delivered single-session group intervention to modify the pain trajectory for individuals with early MS. Research Method/Design: This was a single-center 2-group pilot randomized (1:1) controlled trial comparing a novel videoconference-delivered single-session pain intervention to a waitlist control. Participants were = 27 adults who were diagnosed with MS in the preceding 36 months and who had moderate or worse pain. The study team developed the intervention to introduce pain coping and commonly used cognitive, behavioral, and acceptance-based approaches for adaptive coping. Participants completed outcome assessments on pain intensity, interference, and coping at pretreatment, posttreatment, and 3-months posttreatment.

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