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Prior pain exposure and mere possession of a placebo analgesic predict placebo analgesia: Findings from a randomised, double-blinded, controlled trial.

A recent study found that merely possessing a placebo analgesic reduces pain. The current study tested for a possible moderator of this effect. Specifically, does the mere possession of a placebo analgesic affect pain for individuals with and without immediate prior experience with the pain task? Healthy participants (N=127) were randomized to prior pain (PP) condition or without prior pain (No-PP) condition. In the PP condition, participants first did a preliminary trial of a cold pressor test (CPT) to induce direct experience with this pain stimulus. Then they were randomized to possess an inert cream described as either an analgesic cream or an anti-itch cream (pain-irrelevant control object). Participants then completed the main CPT. In the No-PP condition, participants underwent identical procedures and randomization except that they did not do a preliminary CPT, thus having no immediate prior CPT pain experience. We found a significant prior pain experience and possession status interaction effect on placebo analgesia. Participants in the No-PP condition showed evidence of lower pain when they merely possessed an analgesic cream than an anti-itch cream. Such mere possession effect was not found in the PP condition. The impact of expectancy and emotion on the underlying process are discussed. PERSPECTIVE: This article presents a novel finding that prior pain exposure and mere possession of a placebo analgesic predicted placebo analgesia. It offers a novel perspective on the time course of placebo effect. It provides practical implications on potential pain intervention for clinicians and paradigm design for researchers of placebo study.

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Differences in personality, perceived stress and physical activity in women with burning mouth syndrome compared to controls.

Objectives Burning mouth syndrome (BMS) is a long-lasting pain condition which is commonly associated with anxiety symptoms and experience of adverse, stressful life events have been reported by those diagnosed with the syndrome. Stress-related biomarkers have been related to personality traits in BMS and a personality with high stress susceptibility and perceived stress may be of importance. Although biopsychosocial approaches are suggested to manage long-lasting orofacial pain, to date little is known about physical activity in women with BMS. The aim of this study was to investigate if personality, perceived stress and physical activity distinguish women with BMS from controls. Methods Fifty-six women with BMS and 56 controls matched on age and gender completed Swedish universities Scales of Personality (SSP), Perceived Stress Questionnaire (PSQ) and a general questionnaire with an item on weekly physical activity frequency. In addition, health-related quality of life was explored by additional questionnaires and reported in a companion article (Jedel et al. Scand J Pain. 2020. PubMed PMID: 32853174). Results SSP subscales Somatic Trait Anxiety, Psychic Trait Anxiety, Stress Susceptibility and Verbal Trait Aggression differed between women with BMS and controls and the personality factor scores for Neuroticism and Aggressiveness were higher. Perceived stress measured by PSQ index was higher for women with BMS compared to controls. Women with BMS reported lower physical activity frequency compared to controls and those reporting physical activity <4 days/week scored higher on PSQ compared to those with weekly physical activity ≥4 days/week. Conclusions Personality distinguished women with BMS from controls in this study. Perceived stress was higher and weekly physical activity was lower in women with BMS compared to controls. Our findings suggest physical activity should be more comprehensively measured in future BMS studies and, by extension, physical activity may be a treatment option for women with BMS. Pain management aiming to restore function and mobility with stress reduction should be considered in clinical decision making for women with BMS who have a personality with stress susceptibility, especially if reporting high perceived stress and insufficient physical activity.

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Effectiveness of onabotulinumtoxinA (BOTOX) in pediatric patients experiencing migraines: a randomized, double-blinded, placebo-controlled crossover study in the pediatric pain population.

OnabotulinumtoxinA (OBTA) is approved for treating chronic headaches and migraines in adults, but there is limited scientific literature on the outcomes in pediatric patients. The aim of this study was to determine if subjects treated with OBTA reported a statistically significant improvement in the primary features (frequency, intensity, duration and disability scoring) associated with migraines compared with placebo at follow-up visits.

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Digital Pain Mapping and Tracking in Patients With Chronic Pain: Longitudinal Study.

Digital pain mapping allows for remote and ecological momentary assessment in patients over multiple time points spanning days to months. Frequent ecological assessments may reveal tendencies and fluctuations more clearly and provide insights into the trajectory of a patient's pain.

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Altered trigeminal pain processing on brainstem level in persistent idiopathic facial pain.

Persistent Idiopathic Facial Pain (PIFP) is a poorly understood chronic pain syndrome of the face, formerly known as atypical facial pain. It is characterized by a constant painful sensation without neurological abnormalities and without clinically objectifiable cause. Similarities to neuropathic pain conditions have been discussed and are currently thought to be relevant for the pathophysiology of this disease. In this study we aim to characterize the trigeminal pain processing in PIFP via functional magnetic resonance imaging (fMRI) of the brainstem.25 patients suffering from PIFP and 25 healthy controls (HC) underwent a standardized and well-established paradigm of painful stimulation of the trigeminal nerve using gaseous ammonia. Functional images were acquired within a 3T MRI scanner using an optimized protocol for high resolution echoplanar brainstem imaging.PIFP patients show exclusively a stronger activation to painful stimulation in the spinal trigeminal nucleus (sTN) when contrasted against HC.Our data suggest that abnormal central pain processing plays a role in the pathophysiology of PIFP. An integration of these findings into neuropathic pain models might help to gain a better general understanding of the pathophysiology of PIFP.

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The effect of temporal information on placebo analgesia and nocebo hyperalgesia.

Expectations are known to be key determinants of placebo and nocebo phenomena. In previous studies, verbal suggestions to induce such expectations have mainly focused on the direction and magnitude of the effect while little is known about the influence of temporal information.

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Altered network architecture of functional brain communities in chronic nociplastic pain.

Neuroimaging has enhanced our understanding of the neural correlates of pain. Yet, how neural circuits interact and contribute to persistent pain remain largely unknown. Here, we investigate the mesoscale organization of the brain through intrinsic functional communities generated from resting state functional MRI data from two independent datasets, a discovery cohort of 43 Fibromyalgia (FM) patients and 20 healthy controls (HC) as well as a replication sample of 34 FM patients and 21 HC. Using normalized mutual information, we found that the global network architecture in chronic pain patients is less stable (more variable). Subsequent analyses of node community assignment revealed the composition of the communities differed between FM and HC. Furthermore, differences in network organization were associated with the changes in the composition of communities between patients with varying levels of clinical pain. Together, this work demonstrates that intrinsic network communities differ substantially between patients with FM and controls. These differences may represent a novel aspect of the pathophysiology of chronic nociplastic pain.

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Predictors of engagement in an internet-based cognitive behavioral therapy program for veterans with chronic low back pain.

Internet-based interventions for chronic pain have demonstrated efficacy and may address access barriers to care. Participant characteristics have been shown to affect engagement with these programs; however, limited information is available about the relationship between participant characteristics and engagement with internet-based programs for self-management of chronic pain. The current study examined relationships between demographic and clinical characteristics and engagement with the Pain EASE program, a self-directed, internet-based cognitive behavioral therapy intervention for veterans with chronic low back pain (cLBP). Veterans with cLBP were enrolled in a 10 week trial of the Pain EASE program. Engagement measures included the number of logins, access to coping skill modules, and completed study staff-initiated weekly check-in calls. Regression analyses were conducted to identify significant predictors of engagement from hypothesized predictors (e.g., race/ethnicity, age, depressive symptom severity, and pain interference). Participants (N = 58) were 93% male, 60.3% identified as White, and had a mean age of 54.5 years. Participants logged into the program a median of 3.5 times, accessed a median of 2 skill modules, and attended a median of 6 check-in calls. Quantile regression revealed that, at the 50th percentile, non-White-identified participants accessed fewer modules than White-identified participants (p = .019). Increased age was associated with increased module use (p = .001). No clinical characteristics were significantly associated with engagement measures. White-identified race/ethnicity and increased age were associated with greater engagement with the Pain EASE program. Results highlight the importance of defining and increasing engagement in internet-delivered pain care.

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Will that hurt? A contingency learning task to assess pain-expectancy judgments for low back postures.

Contingency learning, i.e. learning that a cue predicts the presence (or absence) of an event, is central to the formation of beliefs regarding painfulness of body postures. Such beliefs may spread to safe cues due to compromised learning (e.g., excessive generalization, impaired safety learning), prompting avoidance and leading to disability. Despite its importance, compromised learning about low back pain is underinvestigated. We propose a low back pain scenario contingency learning task for the investigation of back pain-related learning.

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Exome Sequencing Implicates Impaired GABA Signaling and Neuronal Ion Transport in Trigeminal Neuralgia.

Trigeminal neuralgia (TN) is a common, debilitating neuropathic face pain syndrome often resistant to therapy. The familial clustering of TN cases suggests that genetic factors play a role in disease pathogenesis. However, no unbiased, large-scale genomic study of TN has been performed to date. Analysis of 290 whole exome-sequenced TN probands, including 20 multiplex kindreds and 70 parent-offspring trios, revealed enrichment of rare, damaging variants in GABA receptor-binding genes in cases. Mice engineered with a TN-associated mutation (p.Cys188Trp) in the GABA receptor Cl channel γ-1 subunit () exhibited trigeminal mechanical allodynia and face pain behavior. Other TN probands harbored rare damaging variants in Na and Ca channels, including a significant variant burden in the α-1H subunit of the voltage-gated Ca channel Ca3.2 (). These results provide exome-level insight into TN and implicate genetically encoded impairment of GABA signaling and neuronal ion transport in TN pathogenesis.

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