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Increased acute postoperative pain intensity has been associated with the development of persistent postsurgical pain (PPP) in mechanistic and clinical investigations, but it remains unclear which aspects of acute pain explain this linkage.
Learn More >The serotonin receptor 2A (HTR2A) has been described as an important facilitation mediator of spinal nociceptive processing leading to central sensitization (CS) in animal models of chronic pain. However, whether HTR2A single nucleotide variants (SNVs) modulate neuropathic pain states in patients has not been investigated so far. The aim of this study was to elucidate the potential association of HTR2A variants with sensory abnormalities or ongoing pain in neuropathic pain patients.
Learn More >For more than ten years, gene therapy for neurological diseases has experienced intensive research growth and more recently therapeutic interventions for multiple indicationsBeneficial results in several phase 1/2 clinical studies, together with improved vector technology have advanced gene therapy for the central nervous system (CNS) in a new era of development. While most initial strategies have focused on orphan genetic diseases, such as lysosomal storage diseases, more complex and widespread conditions like Alzheimer's disease, Parkinson's disease, epilepsy or chronic pain are increasingly targeted for gene therapy. Increasing numbers of applications and patients to be treated will require improving and simplifying gene therapy protocols to make them accessible to the largest number of affected people. While vectors and manufacturing are a major field of academic research and industrial development, there is a growing need to improve, standardize and simplify delivery methods. Delivery is the major issue for CNS therapies in general, and particularly for gene therapy. The blood brain barrier restricts the passage of vectors; and strategies to bypass this obstacle are a central focus of research. Here, we present the different ways that can be used to deliver gene therapy products to the CNS. We focus on results obtained in large animals that have allowed the transfer of protocols to human patients and have resulted in the generation of clinical data. We discuss the different routes of administration, their advantages and their limitations. We describe techniques, equipment and protocols and how they should be selected for safe delivery and improved efficiency for the next generation of gene therapy trials for CNS diseases.
Learn More >Migraine affects how the brain processes sensory information at multiple levels. The aberrant integration of visual and somatosensory stimuli is thought to underlie Alice in Wonderland Syndrome, a disorder often reported as being associated with migraine. However, there is still a lack of knowledge about the epidemiology of this syndrome in migraineurs and the association between Alice in Wonderland Syndrome episodes and migraine attacks. Therefore, we conducted a prospective cohort study to systematically evaluate the prevalence and the clinical features of Alice in Wonderland Syndrome in a large sample of patients with migraine.
Learn More >Rheumatoid arthritis (RA) is chronic, painful, disabling condition resulting in significant impairments in physical, emotional, and social health. We used different methods and perspectives to evaluate the responsiveness of PROMIS® short forms (SFs) and identify minimal and meaningful score changes.
Learn More >The current knowledge on the role of SI and ACC in acute pain processing and how these contribute to the development of chronic pain is limited. Our objective was to investigate differences in and modulation of intracortical responses from SI and ACC in response to different intensities of peripheral presumed noxious and non-noxious stimuli in the acute time frame of a peripheral nerve injury in rats.
Learn More >The relationship between habitual physical activity (PA) and experimental pain tolerance has been investigated in small samples of young, healthy, and/or single-sex volunteers. We used a large, population-based sample to assess this relationship in men and women with and without chronic pain.
Learn More >To determine the onset of preventive efficacy with eptinezumab in patients with migraine.
Learn More >The transient receptor potential vanilloid-1 (TRPV1) is a non-specific cation channel known for its sensitivity to pungent vanilloid compound (i.e. capsaicin) and noxious stimuli, including heat, low pH or inflammatory mediators. TRPV1 is found in the somatosensory system, particularly primary afferent neurons that respond to damaging or potentially damaging stimuli (nociceptors). Stimulation of TRPV1 evokes a burning sensation, reflecting a central role of the channel in pain. Pharmacological and genetic studies have validated TRPV1 as a therapeutic target in several preclinical models of chronic pain, including cancer, neuropathic, postoperative and musculoskeletal pain. While antagonists of TRPV1 were found to be a valuable addition to the pain therapeutic toolbox, their clinical use has been limited by detrimental side effects, such as hyperthermia. In contrast, capsaicin induces a prolonged defunctionalisation of nociceptors and thus opened the door to the development of a new class of therapeutics with long-lasting pain-relieving effects. Here we review the list of TRPV1 agonists undergoing clinical trials for chronic pain management, and discuss new indications, formulations or combination therapies being explored for capsaicin. While the analgesic pharmacopeia for chronic pain patients is ancient and poorly effective, modern TRPV1-targeted drugs could rapidly become available as the next generation of analgesics for a broad spectrum of pain conditions.
Learn More >Metformin is currently first line therapy for type 2 diabetes (T2D). The mechanism of action of metformin involves activation of AMP-activated protein kinase (AMPK) to enhance mitochondrial function (for example, biogenesis, refurbishment and dynamics) and autophagy. Many neurodegenerative diseases of the central and peripheral nervous systems arise from metabolic failure and toxic protein aggregation where activated AMPK could prove protective. Areas covered: The authors review literature on metformin treatment in Parkinson's disease, Huntington's disease and other neurological diseases of the CNS along with neuroprotective effects of AMPK activation and suppression of the mammalian target of rapamycin (mTOR) pathway on peripheral neuropathy and neuropathic pain. The authors compare the efficacy of metformin with the actions of resveratrol. Expert opinion: Metformin, through activation of AMPK and autophagy, can enhance neuronal bioenergetics, promote nerve repair and reduce toxic protein aggregates in neurological diseases. A long history of safe use in humans should encourage development of metformin and other AMPK activators in preclinical and clinical research. Future studies in animal models of neurological disease should strive to further dissect in a mechanistic manner the pathways downstream from metformin-dependent AMPK activation, and to further investigate mTOR dependent and independent signaling pathways driving neuroprotection.
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