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Patients with tension-type headache (TTH) are characterized by recurrent pain that can become disabling. Identifying the dietary triggers of headaches has led to defining dietary strategies to prevent this disease. In fact, excessive dietary intake of Omega-6 (ω-6) fatty acids, or an ω-6: ω3 ≥ 5 ratio, typical of Western diets, has been associated with a higher prevalence of headaches. The objectives of the present study were to compare dietary fatty acid intake between participants with and without chronic TTH and to investigate the association between dietary fatty acid intake, pain characteristics, and quality of life in patients with chronic TTH.
Learn More >Migraine is a multifactorial headache disorder. Maladaptive functional networks or altered circuit-related connectivity in the brain with migraine appear to perturb the effects of usual treatments.
Learn More >Headaches occur when cerebrospinal fluid (CSF) pressure drops following dural puncture or trauma or spontaneously. As the features of these headaches and their accompanying symptoms might not be typical, low CSF pressure headache syndromes, and spontaneous intracranial hypotension in particular, are often misdiagnosed and underdiagnosed.
Learn More >The voltage-gated sodium channel isoform NaV1.7 is a critical player in the transmission of nociceptive information. This channel has been heavily implicated in human genetic pain disorders and is a validated pain target. However, targeting this channel directly has failed, and an indirect approach – disruption of interactions with accessory protein partners – has emerged as a viable alternative strategy. We recently reported that a small-molecule inhibitor of CRMP2 SUMOylation, compound , selectively reduces NaV1.7 currents in DRG neurons across species from mouse to human. This compound also reversed mechanical allodynia in a spared nerve injury and chemotherapy-induced model of neuropathic pain. Here, we show that oral administration of reverses mechanical allodynia in a chronic constriction injury (CCI) model of neuropathic pain. Furthermore, we show that orally administered reverses the increased latency to cross an aversive barrier in a mechanical conflict-avoidance task following CCI. These two findings, in the context of our previous report, support the conclusion that is a robust inhibitor of NaV1.7 function with the ultimate effect of profoundly ameliorating mechanical allodynia associated with nerve injury. The fact that this was observed using both traditional, evoked measures of pain behavior as well as the more recently developed operator-independent mechanical conflict-avoidance assay increases confidence in the efficacy of -induced anti-nociception.
Learn More >Chronic pain is a common and growing problem in the United States with variable strategies for its treatment. Surgical interventions are necessary in some cases but not required for all patients with new-onset pain. For some patients, interventional pain management (IPM) techniques can treat chronic pain without the cost or risk associated with surgical intervention.
Learn More >Irregular regeneration or inappropriate remodeling of the axons of the primary afferent neurons after peripheral nerve trauma could be associated with the development of neuropathic pain. We analyzed the molecular mechanisms for the neuritogenesis and neurite outgrowth caused by prostaglandin E (PGE) in mouse dorsal root ganglion (DRG) neurons, and evaluated their opioid modulation. PGE in combination with IBMX, a phosphodiesterase inhibitor, caused neuritogenesis/neurite outgrowth in DRG cells, an effect abolished by a prostanoid EP, but not EP, receptor antagonist, and inhibitors of adenylyl cyclase or protein kinase A (PKA). Blockers of T-type Ca channels (T-channels), that are responsible for window currents involving the sustained low-level Ca entry at voltages near the resting membrane potentials and can be functionally upregulated by PKA, inhibited the neuritogenesis/neurite outgrowth caused by PGE/IBMX or dibutylyl cyclic AMP, a PKA activator, in DRG neurons, an inhibitory effect mimicked by ZnCl and ascorbic acid that block Ca3.2, but not Ca3.1 or Ca3.3, T-channels. Morphine and DAMGO, μ-opioid receptor (MOR) agonists, suppressed the neuritogenesis and/or neurite outgrowth induced by PGE/IBMX in DRG neurons and also DRG neuron-like ND7/23 cells, an effect reversed by naloxone or β-funaltrexamine, a selective MOR antagonist. Our data suggest that the EP receptor/PKA/Ca3.2 pathway is involved in the PGE-induced neuritogenesis/neurite outgrowth in DRG neurons, which can be suppressed by MOR stimulation. We propose that MOR agonists including morphine in the early phase after peripheral nerve trauma might delay the axonal regeneration of the primary afferent neurons but prevent the development of neuropathic pain.
Learn More >Acute cholecystitis (AC) is an acute inflammatory disease of gallbladder and it is one of the most common causes of acute abdominal pain. Determining the severity of AC at hospital admission is extremely important to choose the most effective treatment method and predict vital prognosis. The aim of this study was to investigate the effectiveness of immature granulocyte percentage (IG%) in grading AC severity.
Learn More >Low-back pain (LBP) is a major public health problem globally and its direct and indirect healthcare costs are growing rapidly. Virtual reality involving the use of video games or non-game applications are alternatives to conventional face-to-face physical therapy for LBP. The purpose of this study was to assess the cost-effectiveness of Back Extension-Virtual Reality Game (BE-VRG) compared to Clinic-based McKenzie therapy (CBMT) for chronic non-specific LBP in Nigeria.
Learn More >Preclinical pain research has applied state-of-the-art methods over the past 40 years to describe, characterize, and image molecules, cells, and circuits in rodents to understand the pathophysiology of chronic pain. Despite generating a plethora of novel analgesic targets, pharmaceuticals for chronic pain treatment remain largely limited to the same 6 drug classes as present 40 years ago. It is possible that 40 years of effort has brought us to the verge of a paradigm shift and an explosion of novel analgesic drug classes with remarkable safety, efficacy, and tolerability. We think it more likely that advances will not occur until we follow the description of exciting discoveries with hypothesis testing using clinically relevant preclinical animal models and ethologically relevant outcome measures, which better reflect the clinical characteristics of chronic pain syndromes. Furthermore, to be valuable, experiments using such models must be conducted to the highest levels of internal validity, rigor, and reproducibility. Efforts by funders, most recently the Helping End Addiction Long-Term by the National Institutes of Health, aim to address some of these challenges and enhance communication and collaboration between preclinical and clinical investigators. However, the greater problem is a culture that emphasizes novelty and number of publications over scientific rigor and robust replication leading to a high likelihood of false-positive results. A path forward is provided by the evolution of clinical research beginning 50 years ago that resulted in methods to reduce bias and enhance transparency and ethics of reporting, moving from case reports to randomized controlled trials to innovative study designs with a focus on rigor, generalizability, and reproducibility. We argue that culture changed in clinical science in part because powerful forces outside the peer review system, especially from federal regulators that approve new drugs and human studies committees that addressed ethical failures of earlier research, mandated change in studies within their purview. Whether an external force will affect change in peclinical pain research is unclear.
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