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It has been established that the endogenous cannabinoid (endocannabinoid) system plays key modulatory roles in a wide variety of pathological conditions. The endocannabinoid system comprises both cannabinoid receptors, their endogenous ligands including 2-arachidonoylglycerol (2-AG), N-arachidonylethanolamine (anandamide, AEA), and enzymes that regulate the synthesis and degradation of endogenous ligands which include diacylglycerol lipase alpha (DAGL-α), diacylglycerol lipase beta (DAGL-β), fatty acid amide hydrolase (FAAH), monoacylglycerol lipase (MAGL), α/β hydrolase domain 6 (ABHD6). As the endocannabinoid system exerts considerable involvement in the regulation of homeostasis and disease, much effort has been made towards understanding endocannabinoid-related mechanisms of action at cellular, physiological, and pathological levels as well as harnessing the various components of the endocannabinoid system to produce novel therapeutics. However, drug discovery efforts within the cannabinoid field have been slower than anticipated to reach satisfactory clinical endpoints and raises an important question into the validity of developing novel ligands that therapeutically target the endocannabinoid system. To answer this, we will first examine evidence that supports the existence of an endocannabinoid system role within inflammatory diseases, neurodegeneration, pain, substance use disorders, mood disorders, as well as metabolic diseases. Next, this review will discuss recent clinical studies, within the last 5 years, of cannabinoid compounds in context to these diseases. We will also address some of the challenges and considerations within the cannabinoid field that may be important in the advancement of therapeutics into the clinic.
Learn More >Brainhack is an innovative meeting format that promotes scientific collaboration and education in an open, inclusive environment. This NeuroView describes the myriad benefits for participants and the research community and how Brainhacks complement conventional formats to augment scientific progress.
Learn More >Fatigue is a cardinal symptom in fibromyalgia. Fatigue is assumed to be the result of genetic susceptibility and environmental factors. We aimed at examining the role of genetic susceptibility for fatigue in southern Spanish women with fibromyalgia, by looking at single nucleotide polymorphisms in 34 fibromyalgia candidate-genes, at the interactions between genes, and at the gene-physical activity interactions. We extracted DNA from saliva of 276 fibromyalgia women to analyze gene-polymorphisms. Accelerometers registered physical activity and sedentary behavior. Fatigue was assessed with the Multidimensional Fatigue Inventory. Based on the Bonferroni's and False Discovery Rate values, we found that the genotype of the rs4453709 polymorphism (sodium channel protein type 9 subunit alpha, , gene) was related to reduced motivation (AT carriers showed the highest reduced motivation) and reduced activity (AA carriers showed the lowest reduced activity). Carriers of the heterozygous genotype of the rs1801133 (methylene tetrahydrofolate reductase, , gene) or rs4597545 ( gene) polymorphisms who were physically active reported lower scores on fatigue compared to their inactive counterparts. Highly sedentary carriers of the homozygous genotype of the rs7607967 polymorphism (AA/GG genotype; gene) presented more reduced activity (a dimension of fatigue) than those with lower levels of sedentary behavior. Collectively, findings from the present study suggest that the contribution of genetics and gene-physical activity interaction to fatigue in fibromyalgia is modest.
Learn More >To report the efficacy and safety of erenumab among episodic migraine (EM) patients who were unsuccessful on 2-4 preventive treatments observed at week 64 of Open-Label Extension Phase (OLEP) of the LIBERTY study (ClinicalTrials.gov NCT03096834).
Learn More >To assess photophobia and allodynia in subjects with post-traumatic headache and examine how these sensory hypersensitivities associate with clinical measures of disease burden.
Learn More >Descending pain modulation involves multiple encephalic sites and pathways that range from the cerebral cortex to the spinal cord. Behavioral studies conducted in the 1980s revealed that electrical stimulation of the pretectal area causes antinociception dissociation from aversive responses. Anatomical and physiological studies identified the anterior pretectal nucleus and its descending projections to several midbrain, pontine, and medullary structures. The anterior pretectal nucleus is morphologically divided into a dorsal part that contains a dense neuron population (pars compacta) and a ventral part that contains a dense fiber band network (pars reticulata). Connections of the two anterior pretectal nucleus parts are broad and include prominent projections to and from major encephalic systems associated with somatosensory processes. Since the first observation that acute or chronic noxious stimuli activate the anterior pretectal nucleus, it has been established that numerous mediators participate in this response through distinct pathways. Recent studies have confirmed that at least two pain inhibitory pathways are activated from the anterior pretectal nucleus. This review focuses on rodent anatomical, behavioral, molecular and neurochemical data that have helped to identify mediators of the anterior pretectal nucleus and pathways related to its role in pain modulation.
Learn More >The use of paracetamol or nefopam for postoperative pain control is limited by the need of high doses associated with unwanted effects. Previous works suggest positive interactions between both compounds that may be exploited to obtain potentiation of antinociception.
Learn More >Neck and shoulder pain in adolescents seldom occur alone: results from the Norwegian Ungdata Survey.
No previous studies have investigated the prevalence of co-occurring neck/shoulder pain, other musculoskeletal pain, headache, and depressive symptoms in adolescents. This study aimed to describe the prevalence of isolated neck/shoulder pain and the co-occurrence of neck/shoulder pain with other musculoskeletal pain, headache, and depressive symptoms in Norwegian adolescents.
Learn More >The multifaceted clinical presentation of fibromyalgia (FM) supports the modern understanding of the disorder as a more global condition than one simply affecting pain sensation. The main pharmacologic therapies used clinically include anti-epileptics and anti-depressants. Conservative treatment options include exercise, myofascial release, psychotherapy, and nutrient supplementation.
Learn More >Despite the pivotal role of psychosocial factors in pain and disability after orthopedic injury, there are no evidence-based preventive interventions targeting psychosocial factors in patients with acute orthopedic injuries. We developed the first mind-body intervention focused on optimizing recovery and improving pain and disability in patients with acute orthopedic injuries who exhibit high levels of catastrophic thinking about pain and/or pain anxiety (Toolkit for Optimal Recovery [TOR] after orthopedic injury). In a pilot single-site randomized controlled trial (RCT), the TOR met a priori set benchmarks for feasibility, acceptability, and satisfaction. The next step in developing TOR is to conduct a multisite feasibility RCT to set the stage for a scientifically rigorous hybrid efficacy-effectiveness trial.
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