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Osteoarthritis (OA) is a chronic degenerative musculoskeletal disease that causes articular damage and chronic pain, with a prevalence of up to 50% in individuals >60 years of age. Patients suffering from chronic painful conditions, including OA, also frequently report anxiety or depression. A systematic review and meta-analysis were performed to assess the correlation between pain severity and depressive and anxious symptomatology in OA patients.
Learn More >: In the absence of head-to-head comparisons, the objective of this study was to conduct a network meta-analysis (NMA) to indirectly compare the relative efficacy and safety of rimegepant, ubrogepant, and lasmiditan for the acute treatment of migraine. : A systematic literature review was conducted to identify randomized controlled trials (RCTs) of rimegepant, ubrogepant and lasmiditan in adults with acute migraine. Outcomes included sustained pain freedom and -relief 2-48 hours post-dose, and adverse events. No RCTs were identified that directly compared these interventions. Therefore, a fixed-effects Bayesian NMA was conducted by identifying a connected (via comparison to placebo) network of RCTs. : Five RCTs were identified: rimegepant study 303 (n=1,466), ubrogepant ACHIEVE I and II (n=1,672 and n=1,686, respectively), and lasmiditan SAMURAI and SPARTAN (n=2,231 and n=3,005, respectively). Efficacy outcomes (pain freedom and relief at 2, 24, 48 hours) tended to be highest for lasmiditan 200 mg and rimegepant followed lower doses of lasmiditan and all doses of ubrogepant. However, lasmiditan 200 mg was also associated with higher rates of adverse events, particularly somnolence and dizziness. : Lasmiditan, rimegepant, and ubrogepant all performed significantly better than placebo with respect to pain freedom and pain relief. Efficacy results were similar for rimegepant and lasmiditan with rimegepant having higher rates of pain freedom and relief than lower doses of lasmiditan, while somnolence and dizziness outcomes were lower for rimegepant than higher doses of lasmiditan.
Learn More >It is well established that migraine is a multifactorial disorder. A deep understanding of migraine should be based upon both the underlying traits and the current states affected by different physiological, psychological, and environmental factors. At this point, there is no framework fully meeting these criteria. Here, we describe a broader view of the migraine disorder defined as a dysfunctional brain state and trait interaction. In this model, we consider events that may enhance or diminish migraine responsivity based on an individual's trait and state. This could provide an expanded view for considering how migraine attacks are sometimes precipitated by "triggers" and sometimes not, how these factors only lead to migraine attacks in migraine patients, or how individuals with an increased risk for migraine do not show any symptoms at all. Summarizing recent studies and evidence that support the concept of migraine as a brain state-trait interaction can also contribute to improving patient care by highlighting the importance of precision medicine and applying measures that are able to capture how different traits and states work together to determine migraine.
Learn More >The aim of this study was to investigate the effect on observationally acquired placebo analgesia of a model's self-confidence as well as the observer's self-esteem and self-efficacy. In addition, we aimed to verify the stability of the placebo effect induced by observational learning. Participants (N = 60) were randomly assigned to one of three groups: a self-confident model, an unself-confident model, and a control group. In the experimental groups, participants watched a videotaped model who rated the intensity of electrocutaneous pain stimuli applied in the placebo condition as lower than those applied in the non-placebo condition. The different levels of self-confidence in these groups were manifested in the body posture and facial expressions of the model as well as in specific behavior that accompanied the assessment of pain. Then, 16 electrocutaneous pain stimuli of the same intensity, preceded by the placebo or non-placebo, were applied to participants. In both experimental groups, in contrast to the control group, participants experienced less pain in the placebo than in the non-placebo condition. Although the magnitude of placebo analgesia did not differ between the experimental groups, multiple regression analysis revealed that the perceived self-confidence of the model, but not the self-efficacy or self-esteem of the observer, was a significant predictor of the placebo effect. Moreover, placebo analgesia induced by observational learning did not extinguish over the course of the experiment. These results support the premise that the observers' perception of a model's self-confidence plays a significant role in placebo effects. PERSPECTIVE: The results of this study open the discussion on the role of model's features in the effectiveness of observational learning in the induction of placebo effects. The study provides the very first suggestion that the perceived self-confidence of the model may be related to the magnitude of the observationally induced placebo analgesia. It suggests that self-confidence of other patients and medical staff might affect individual pain experiences.
Learn More >Chronic neuropathic pain affects 7%-10% of the population. Deep brain stimulation (DBS) has shown variable but promising results in its treatment. This study prospectively assessed the long-term effectiveness of DBS in a series of patients with chronic neuropathic pain, correlating clinical results with neuroimaging. Sixteen patients received 5 years' post-surgical follow-up in a single center. Six had phantom limb pain after amputation and 10 had deafferentation pain after traumatic brachial plexus injury. Patient-reported outcome measures were completed before and after surgery, using VAS, UWNPS, BPI and SF-36 scores. Neuroimaging evaluated electrode location and effective volumes of activated tissue (VAT). Two subgroups were created based on the percentage of VAT superimposed upon the ventroposterolateral thalamic nucleus (eVAT), and clinical outcomes were compared. Analgesic effect was assessed at 5 years and compared to preoperative pain, with an improvement on VAS of 76.4% (p = 0.0001), on UW-NPS of 35.2% (p = 0.3582), on BPI of 65.1% (p = 0.0505) and on SF-36 of 5% (p = 0.7406). Eight patients with higher eVAT showed improvement on VAS of 67.5% (p=0.0017) while the remaining patients, with lower eVAT, improved by 50.6% (p=0.03607). DBS remained effective in improving chronic neuropathic pain after 5 years. While VPL-targeting contributes to success, analgesia is also obtained by stimulating surrounding posterior ventrobasal thalamic structures and related spinothalamocortical tracts.
Learn More >Chronic pain is characterized by discrete pain episodes of unpredictable frequency and duration. This hinders the study of pain mechanisms and contributes to the use of pharmacological treatments associated with side effects, addiction and drug tolerance. Here, we show that a closed-loop brain-machine interface (BMI) can modulate sensory-affective experiences in real time in freely behaving rats by coupling neural codes for nociception directly with therapeutic cortical stimulation. The BMI decodes the onset of nociception via a state-space model on the basis of the analysis of online-sorted spikes recorded from the anterior cingulate cortex (which is critical for pain processing) and couples real-time pain detection with optogenetic activation of the prelimbic prefrontal cortex (which exerts top-down nociceptive regulation). In rats, the BMI effectively inhibited sensory and affective behaviours caused by acute mechanical or thermal pain, and by chronic inflammatory or neuropathic pain. The approach provides a blueprint for demand-based neuromodulation to treat sensory-affective disorders, and could be further leveraged for nociceptive control and to study pain mechanisms.
Learn More >Erenumab is a human anti-calcitonin gene-related peptide receptor monoclonal antibody approved for migraine prevention. Global studies have demonstrated its efficacy in chronic and episodic migraine (EM). Here we report the outcomes from a Phase 3 study of erenumab in Japanese patients with chronic migraine (CM) or EM.
Learn More >The adenosine triphosphate-binding cassette, subfamily B, member 1 gene (ABCB1) encodes P-glycoprotein (P-gp) that influences the intracellular transport of solutes including endogenous opioid peptides. The primary objective of this study was to determine the effects of the ABCB1 polymorphism c.3435C>T (rs10454642) on heat pain (HP) perception in a group of opioid-free adults with chronic pain.
Learn More >Insights into T cell form, function, and dysfunction are rapidly evolving. T cells have remarkably varied effector functions including protecting the host from infection, activating cells of the innate immune system, releasing cytokines and chemokines, and heavily contributing to immunological memory. Under healthy conditions, T cells orchestrate a finely tuned attack on invading pathogens while minimizing damage to the host. The dark side of T cells is that they also exhibit autoreactivity and inflict harm to host cells, creating autoimmunity. The mechanisms of T cell autoreactivity are complex and dynamic. Emerging research is elucidating the mechanisms leading T cells to become autoreactive and how such responses cause or contribute to diverse disease states, both peripherally and within the central nervous system. This review provides foundational information on T cell development, differentiation, and functions. Key T cell subtypes, cytokines that create their effector roles, and sex differences are highlighted. Pathological T cell contributions to diverse peripheral and central disease states, arising from errors in reactivity, are highlighted, with a focus on multiple sclerosis, rheumatoid arthritis, osteoarthritis, neuropathic pain, and type 1 diabetes.
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