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Predicting treatment adherence and outcome to outpatient multimodal rehabilitation in chronic low back pain.

There is a growing need to identify patient pre-treatment characteristics that could predict adherence and outcome following specific interventions.

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The spectrum of response to erenumab in patients with chronic migraine and subgroup analysis of patients achieving ≥50%, ≥75%, and 100% response.

To assess the efficacy of erenumab across the spectrum of response thresholds (≥50%, ≥75%, 100%) based on monthly migraine days (MMD) reduction in patients with chronic migraine from a 12-week, randomized study (NCT02066415).

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Generalization of instrumentally acquired pain-related avoidance to novel but similar movements using a robotic arm-reaching paradigm.

Avoidance is considered a key contributor to the development and maintenance of chronic pain disability, likely through its excessive generalization. This study investigated whether acquired avoidance behavior generalizes to novel but similar movements. Using a robotic arm, participants moved their arm from a starting to a target location via one of three possible movement trajectories. For the Experimental Group, the shortest, easiest trajectory was always paired with pain (T1 = 100% reinforcement/no resistance and deviation). Pain could be partly or completely avoided by choosing increasingly effortful movements (T2 = 50% reinforcement, moderate resistance/deviation; T3 = 0% reinforcement, strongest resistance/largest deviation). A Yoked Group received the same number of painful stimuli irrespective of their own behavior. Outcomes were self-reported fear of movement-related pain, pain-expectancy, avoidance behavior, (maximal deviation from the shortest trajectory), and trajectory choice behavior. We tested generalization to three novel trajectories (G1-3) positioned next to the acquisition trajectories. Whereas acquired fear of movement-related pain and pain-expectancy generalized in the Experimental Group, avoidance behavior did not, suggesting that threat beliefs and high-cost avoidance may not be directly related. The lack of avoidance generalization may be due to a perceived context-switch in the configurations of the acquisition and the generalization phases.

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Evaluation of the Pharmacokinetic Interaction Between the Voltage- and Use-Dependent Nav1.7 Channel Blocker Vixotrigine and Carbamazepine in Healthy Volunteers.

Vixotrigine is a voltage- and use-dependent Nav1.7 channel blocker under investigation for the treatment of peripheral neuropathic pain conditions, including trigeminal neuralgia. Vixotrigine is metabolized primarily via uridine diphosphate-glucuronosyltransferases (UGTs). Carbamazepine, a UGT and cytochrome P450 3A4 inducer, is a first-line treatment for trigeminal neuralgia. We conducted a double-blind, randomized, placebo-controlled, parallel-group, single-center phase 1 study to investigate the impact of coadministering vixotrigine and carbamazepine on their respective pharmacokinetics (PK) in healthy volunteers, the safety and tolerability of combined treatment, and PK recovery of vixotrigine following carbamazepine discontinuation. Randomly assigned treatments were carbamazepine (100 mg twice a day, days 1-3 and 200 mg twice a day, days 4-21) or placebo on days 1 to 21. All volunteers received vixotrigine 150 mg 3 times a day on days 16 to 28. At prespecified times, whole-blood samples were collected for PK assessment. Statistical analyses were performed on the log-transformed PK parameters area under the concentration-time curve within a dosing interval (AUC ) and maximum observed concentration (C ) for vixotrigine, carbamazepine, and metabolites. Vixotrigine AUC and C were reduced by 31.6% and 26.3%, respectively, when coadministered with carbamazepine compared with placebo. Seven days after carbamazepine discontinuation, vixotrigine AUC and C remained 24.5% and 21.4% lower compared with placebo. Carbamazepine AUC and C were <10% lower when coadministered with vixotrigine compared on days 15 and 21. Vixotrigine/carbamazepine coadministration was well tolerated. These results suggest that vixotrigine does not have an effect on carbamazepine PK, and although carbamazepine has an effect on the exposure of vixotrigine, the effect is not considered clinically relevant.

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Drivers of the opioid crisis: An appraisal of financial conflicts of interest in clinical practice guideline panels at the peak of opioid prescribing.

Starting in the late 1990s, the pharmaceutical industry sought to increase prescribing of opioids for chronic non-cancer pain. Influencing the content of clinical practice guidelines may have been one strategy industry employed. In this study we assessed potential risk of bias from financial conflicts of interest with the pharmaceutical industry in guidelines for opioid prescribing for chronic non-cancer pain published between 2007 and 2013, the peak of opioid prescribing.

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MINDflex Training for Cognitive Flexibility in Chronic Pain: A Randomized, Controlled Cross-Over Trial.

Impairments in executive functioning are prevalent in chronic pain conditions, with cognitive inflexibility being the most frequently reported. The current randomized, cross-over trial, piloted a computerized cognitive training (CCT) program based on Relational Frame Theory, targeting improvement in cognitive flexibility. At baseline, 73 chronic pain patients completed testing on pre-selected outcomes of executive functioning, alongside IQ measures. When tested three times over the course of 5 months, there was a drop-out rate of 40% at the third time point, leaving 44 patients who had data at all time points. The results showed that there was a substantial learning effect from the MINDFLEX training and a substantial time-dependent improvement on the primary outcomes of increased flexibility, but that this could not be tied to active training. In conclusion, this small study indicated a learning effect as well as improvement on primary outcomes. Based on the current results, a larger trial with improved feasibility of training is warranted.

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One of us or one of them? The effects of the model’s and observer’s characteristics on placebo analgesia induced by observational learning.

Previous studies have proved that observational learning can induce placebo analgesia, but the factors that influence observationally induced placebo analgesia have not yet been extensively examined. The primary goal of this study was to investigate the effect of information about the role that the observed person (model) plays in the experiment on the magnitude of the observationally induced placebo effect. This study also examined the contribution of the observer's empathy, conformity and fear of pain to the placebo analgesia induced by observational learning. The effects induced in two experimental groups and one control group were compared. Participants in the experimental groups observed a model introduced as either another participant taking part in the study or a coworker of the experimenter. The model rated the intensity of pain induced by electrocutaneous stimuli preceded by color stimuli. One-half of all participants watched a model rating pain stimuli preceded by the color orange as higher than stimuli preceded by the color blue; for the other half, the ratings were the opposite. There was no observation in the control group. Subsequently, all participants received pain stimuli of the same intensity preceded by orange and blue stimuli and rated the intensity of the experienced pain. Placebo analgesia was found in both experimental groups. However, the way the observed model was introduced to participants did not affect the magnitude of placebo analgesia. Thus, the study showed that the role played by the model is not crucial for observationally induced placebo analgesia. The examined observer's individual characteristics did not predict the magnitude of placebo effect.

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Group Acupuncture Therapy With Yoga Therapy for Chronic Neck, Low Back, and Osteoarthritis Pain in Safety Net Setting for an Underserved Population: Design and Rationale for a Feasibility Pilot.

Chronic pain is prevalent in the United States, with impact on physical and psychological functioning as well as lost work productivity. Minority and lower socioeconomic populations have increased prevalence of chronic pain with less access to pain care, poorer outcomes, and higher risk of fatal opioid overdose. Acupuncture therapy is effective in treating chronic pain conditions including chronic low back pain, neck pain, shoulder pain, and knee pain from osteoarthritis. Acupuncture therapy, including group acupuncture, is feasible and effective, and specifically so for underserved and diverse populations at risk for health outcome disparities. Acupuncture therapy also encourages patient engagement and activation. As chronic pain improves, there is a natural progression to want and need to increase activity and movement recovery. Diverse movement approaches are important for improving range of motion, maintaining gains, strengthening, and promoting patient engagement and activation. Yoga therapy is an active therapy with proven benefit in musculoskeletal pain disorders and pain associated disability. The aim of this quasi-experimental pilot feasibility trial is to test the bundling of these 2 effective care options for chronic pain, to inform both the design for a larger randomized pragmatic effectiveness trial as well as implementation strategies across underserved settings.

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Functional Alterations in the Posterior Insula and Cerebellum in Migraine Without Aura: A Resting-State MRI Study.

: Hypothesis-driven functional connectivity (FC) analyses have revealed abnormal functional interaction of regions or networks involved in pain processing in episodic migraine patients. We aimed to investigate the resting-state FC patterns in episodic migraine by combining data-driven voxel-wise degree centrality (DC) calculation and seed-based FC analysis. : Thirty-nine patients suffering from episodic migraine without aura and 35 healthy controls underwent clinical assessment and functional MRI. DC was analyzed voxel-wise and compared between groups, and FC of regions with DC differences were further examined using a seed-based approach. : Compared with the control group, the migraine group showed increased and decreased DC in the right posterior insula and left crus I, respectively. Seed-based FC analyses revealed that migraine patients demonstrated increased right posterior insula connections with the postcentral gyrus, supplementary motor area/paracentral lobule, fusiform gyrus and temporal pole. The left crus I showed decreased FC with regions of the default mode network (DMN), including the medial prefrontal cortex (mPFC), angular gyrus, medial and lateral temporal cortex in patients with migraine. Furthermore, pain intensity positively correlated with DC in the right amygdala/parahippocampal gyrus, and migraine frequency negatively correlated with FC between the left crus I and mPFC. : Patients with episodic migraine without aura have increased FC with the right posterior insula and decreased FC within the DMN, which may underlie disturbed sensory integration and cognitive processing of pain. The left crus I-mPFC connectivity may be a useful biomarker for assessing migraine frequency.

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Antagonism of CGRP Signaling by Rimegepant at Two Receptors.

The "gepants" are a class of calcitonin gene-related peptide (CGRP) receptor antagonist molecules that have been developed for the prevention and treatment of migraine. Rimegepant is reported to act at the CGRP receptor, has good oral bioavailability, and has had positive clinical trial results. However, there is very little data available describing its receptor pharmacology. Importantly, rimegepant activity at the AMY receptor, a second potent CGRP receptor that is known to be expressed in the trigeminovascular system, has not been reported. The ability of rimegepant to antagonize activation of human CGRP, AMY, and related adrenomedullin receptors was determined in transfected in Cos7 cells. Rimegepant was an effective antagonist at both the CGRP and AMY receptor. The antagonism of both CGRP and AMY receptors may have implications for our understanding of the mechanism of action of rimegepant in the treatment of migraine.

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