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The Ups and Downs of Endocannabinoid Signaling in Chronic Pain-Induced Depression.

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Development and testing of an opioid tapering self-management intervention for chronic pain: I-WOTCH.

To describe the design, development and pilot of a multicomponent intervention aimed at supporting withdrawal of opioids for people with chronic non-malignant pain for future evaluation in the Improving the Wellbeing of people with Opioid Treated CHronic pain (I-WOTCH) randomised controlled trial.

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Mitochondrial Reactive Oxygen Species Elicit Acute and Chronic Itch via Transient Receptor Potential Canonical 3 Activation in Mice.

Mitochondrial reactive oxygen species (mROS) that are overproduced by mitochondrial dysfunction are linked to pathological conditions including sensory abnormalities. Here, we explored whether mROS overproduction induces itch through transient receptor potential canonical 3 (TRPC3), which is sensitive to ROS. Intradermal injection of antimycin A (AA), a selective inhibitor of mitochondrial electron transport chain complex III for mROS overproduction, produced robust scratching behavior in naïve mice, which was suppressed by MitoTEMPO, a mitochondria-selective ROS scavenger, and Pyr10, a TRPC3-specific blocker, but not by blockers of TRPA1 or TRPV1. AA activated subsets of trigeminal ganglion neurons and also induced inward currents, which were blocked by MitoTEMPO and Pyr10. Besides, dry skin-induced chronic scratching was relieved by MitoTEMPO and Pyr10, and also by resveratrol, an antioxidant. Taken together, our results suggest that mROS elicit itch through TRPC3, which may underlie chronic itch, representing a potential therapeutic target for chronic itch.

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The Role of Microglial Purinergic Receptors in Pain Signaling.

Pain is an essential modality of sensation in the body. Purinergic signaling plays an important role in nociceptive pain transmission, under both physiological and pathophysiological conditions, and is important for communication between both neuronal and non-neuronal cells. Microglia and astrocytes express a variety of purinergic effectors, and a variety of receptors play critical roles in the pathogenesis of neuropathic pain. In this review, we discuss our current knowledge of purinergic signaling and of the compounds that modulate purinergic transmission, with the aim of highlighting the importance of purinergic pathways as targets for the treatment of persistent pain.

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Effectiveness of manual therapy in the treatment of cervicogenic headache: A systematic review.

The aim of this study was to identify the manual therapy (MT) methods and techniques that have been evaluated for the treatment of cervicogenic headache (CH) and their effectiveness.

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Analysis of Antidepressant, Benzodiazepine Anxiolytic, and Hypnotic Use When Treating Depression, Anxiety, and Aggression in Pain Clinic Patients Treated for Neuropathic Pain.

Depression, anxiety, and aggression accompany neuropathic pain. Effective treatment of these comorbidities enhances the outcomes of pain management. Therefore, the study was designed to analyze the relationship between the intensity of depression, anxiety, and aggression and the pharmacotherapy applied in the daily practice of treating neuropathic pain. The aim of the study was to evaluate the frequency of using antidepressants (ADs), benzodiazepine anxiolytics (BDAs), and hypnotics, and the influence of administering these on the intensity of depression, anxiety, and aggression in patients diagnosed with neuropathic pain. A multi-center survey was conducted among 421 patients. An evaluation of the severity of depression, anxiety, and aggression was made using the Hospital Anxiety and Depression Scale-Modified Version (HADS-M). Among the patients treated due to neuropathic pain, ADs are used much more often than BDAs and hypnotics. Depression was well controlled, while anxiety was identified as a possible uncontrolled therapeutic problem in these patients, despite the correlation between the frequency of AD and hypnotics usage and the severity of anxiety. We also found that women show a higher level of intensity in both anxiety and depression, but this does not influence the frequency of their being administered ADs, BDAs, and hypnotics.

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Impact of the COVID-19 pandemic on people living with migraine: Results of the MiCOAS qualitative study.

The coronavirus disease 2019 (COVID-19) pandemic is an ongoing global health crisis that has had a range of impacts on people living with migraine.

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New Generation Gepants: Migraine Acute and Preventive Medications.

Migraine is a debilitating disease whose clinical and social impact is out of debate. Tolerability issues, interactions, contraindications, and inefficacy of the available medications make new options necessary. The calcitonin-gene-related peptide (CGRP) pathway has shown its importance in migraine pathophysiology and specific medications targeting this have become available. The first-generation CGRP receptor antagonists or gepants, have undergone clinical trials but their development was stopped because of hepatotoxicity. The new generation of gepants, however, are efficacious, safe, and well tolerated as per recent clinical trials. This led to the FDA-approval of rimegepant, ubrogepant, and atogepant. The clinical trials of the available gepants and some of the newer CGRP-antagonists are reviewed in this article.

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Systemic Immunomodulatory Treatments for Atopic Dermatitis: Update of a Living Systematic Review and Network Meta-analysis.

Systemic treatments for atopic dermatitis are being evaluated primarily in placebo-controlled trials; network meta-analysis can provide relative efficacy and safety estimates for treatments that have not been compared head to head.

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The neglect of sex: A call to action for including sex as a biological variable in placebo and nocebo research.

Sex differences exist in the prevalence, progression and treatment efficacy of a wide array of medical conditions. While the placebo and nocebo effects have become increasingly relevant in the clinical arena, little is known about the influence of biological sex on placebo and nocebo effects. This paper discusses the existing, relatively limited and sometimes conflicting evidence about how sex impacts the occurrence and magnitude of the placebo and nocebo effects, mainly focusing on pain studies. We present recent evidence that when compared to men, women suffering from chronic orofacial pain may derive greater benefit from the placebo effect for analgesia. Nonetheless, we broadly argue that the field is not currently positioned to draw definitive conclusions and propose several important factors that may explain the inconsistency in the literature and that should be taken into account in future research. These include the specific target symptom of the placebo or nocebo manipulation and whether or not the target is related to the medical condition, the placebo or nocebo induction method, the sex of the experimenter or physician, and so forth. Future research should intentionally include sex a biological variable to favor translation of placebo and nocebo mechanisms into clinical applications.

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