Pain
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Randomized Controlled Trial
Pain response to cannabidiol in opioid-induced hyperalgesia, acute nociceptive pain, and allodynia using a model mimicking acute pain in healthy adults in a randomized trial (CANAB II).
Opioids in general and remifentanil in particular can induce hyperalgesia. Preclinical data suggest that cannabidiol might have the capacity to reduce opioid-induced hyperalgesia (OIH). Thus, we investigated the effect of oral cannabidiol on OIH in healthy volunteers using an established pain model. ⋯ Cannabidiol was well tolerated. We conclude that a high single-oral dose of 1600-mg cannabidiol is not effective in reducing OIH. Before excluding an effect of cannabidiol on OIH, research should focus on drug formulations enabling higher cannabidiol concentrations.
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Randomized Controlled Trial
How do placebo effects contribute to mindfulness-based analgesia? Probing acute pain effects and interactions using a randomized balanced placebo design.
Recent sham-controlled studies suggest placebo effects contribute to acute pain relief after mindfulness interventions. However, the specific effects of mindfulness processes and their interaction with placebo effects remain unclear. This study aimed to characterize the role of mindfulness and placebo processes underlying mindfulness-based pain attenuation. ⋯ These findings suggest a lack of specific effects of mindfulness and instruction on acute pain. Nonetheless, participants' expectancies and beliefs about the treatment they received did predict pain relief. Together with the overall improvement after any intervention, these findings suggest that expectancy and belief may play a stronger role in attenuating acute pain in novices following brief mindfulness interventions than the actual mindfulness-specific processes or instructions delivered.
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Randomized Controlled Trial
Non-invasive vagus nerve stimulation modulates trigeminal but not somatosensory perception: functional evidence for a trigemino-vagal system in humans.
Noninvasive vagus nerve stimulation (nVNS) is effective in several types of headache disorders. We sought to unravel the mechanism of how nVNS exhibits this efficacy. This study used a randomized, single-blind, sham-controlled, crossover design and comprised 3 projects with 3 independent cohorts of healthy participants. ⋯ Heart rate variability parameters did not change after nVNS. Our results provide functional evidence of a long hypothesized functional trigemino-vagal system in humans and may explain why nVNS is effective in some headache disorders but not in somatic pain disorders. Because unilateral nVNS modulated the trigeminal thresholds bilaterally, this effect is probably indirect through a central top-down mechanism.
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Randomized Controlled Trial
A prospective, double-blind, pilot randomized controlled trial of an 'embodied' virtual reality intervention for chronic low back pain in adults.
Adults with chronic low back pain, disability, moderate-to-severe pain, and high fear of movement and reinjury were recruited into a trial of a novel, automated, digital therapeutics, virtual reality, psychological intervention for pain (DTxP). We conducted a 3-arm, prospective, double-blind, pilot, randomized, controlled trial comparing DTxP with a sham placebo comparator and an open-label standard care. Participants were enrolled for 6 to 8 weeks, after which, the standard care control arm were rerandomized to receive either the DTxP or sham placebo. ⋯ Standard care did not report any significant changes. There were a number of adverse events, with one participant reporting a serious adverse event in the sham placebo, which was not related to treatment. No substantial changes in medications were noted, and participants in the DTxP group reported positive gaming experiences.
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Randomized Controlled Trial
Evidence for engagement of the nucleus of the solitary tract in processing intestinal chemonociceptive input irrespective of conscious pain response in healthy humans.
Neuroimaging studies have revealed important pathomechanisms related to disorders of brain-gut interactions, such as irritable bowel syndrome and functional dyspepsia. More detailed investigations aimed at neural processing in the brainstem, including the key relay station of the nucleus of the solitary tract (NTS), have hitherto been hampered by technical shortcomings. To ascertain these processes in more detail, we used multiecho multiband 7T functional magnetic resonance imaging and a novel translational experimental model based on a nutrient-derived intestinal chemonociceptive stimulus. ⋯ On the contrary, activations at the level of the NTS were independent of subjective pain ratings. The current experimental paradigm therefore allowed us to demonstrate activation of the principal relay station for visceral afferents in the brainstem, the NTS, which was engaged irrespective of the conscious pain response. These findings contribute to understanding the fundamental mechanism necessary for developing novel therapies aimed at correcting disturbances in visceral afferent pain processing.