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Axons in the central nervous system (CNS) typically fail to regenerate after injury. This failure is multi-factorial and caused in part by disruption of the axonal cytoskeleton. The cytoskeleton, in particular microtubules (MT), plays a critical role in axonal transport and axon growth during development. In this regard, members of the kinesin superfamily of proteins (KIFs) regulate the extension of primary axons toward their targets and control the growth of collateral branches. KIF2A negatively regulates axon growth through MT depolymerization. Using three different injury models to induce SCI in adult rats, we examined the temporal and cellular expression of KIF2A in the injured spinal cord. We observed a progressive increase of KIF2A expression with maximal levels at 10 days to 8 weeks post-injury as determined by Western blot analysis. KIF2A immunoreactivity was present in axons, spinal neurons and mature oligodendrocytes adjacent to the injury site. Results from the present study suggest that KIF2A at the injured axonal tips may contribute to neurite outgrowth inhibition after injury, and that its increased expression in inhibitory spinal neurons adjacent to the injury site might contribute to an intrinsic wiring-control mechanism associated with neuropathic pain. Further studies will determine whether KIF2A may be a potential target for the development of regeneration-promoting or pain-preventing therapies.
Learn More >Migraine can be regarded as a conserved, adaptive response that occurs in genetically predisposed individuals with a mismatch between the brain's energy reserve and workload. Given the high prevalence of migraine, genotypes associated with the condition seem likely to have conferred an evolutionary advantage. Technological advances have enabled the examination of different aspects of cerebral metabolism in patients with migraine, and complementary animal research has highlighted possible metabolic mechanisms in migraine pathophysiology. An increasing amount of evidence – much of it clinical – suggests that migraine is a response to cerebral energy deficiency or oxidative stress levels that exceed antioxidant capacity and that the attack itself helps to restore brain energy homeostasis and reduces harmful oxidative stress levels. Greater understanding of metabolism in migraine offers novel therapeutic opportunities. In this Review, we describe the evidence for abnormalities in energy metabolism and mitochondrial function in migraine, with a focus on clinical data (including neuroimaging, biochemical, genetic and therapeutic studies), and consider the relationship of these abnormalities with the abnormal sensory processing and cerebral hyper-responsivity observed in migraine. We discuss experimental data to consider potential mechanisms by which metabolic abnormalities could generate attacks. Finally, we highlight potential treatments that target cerebral metabolism, such as nutraceuticals, ketone bodies and dietary interventions.
Learn More >Transient disturbances in neurologic function are disturbing features of migraine attacks. Aura types include binocular visual, hemi-sensory, language and unilateral motor symptoms. Because of the gradual spreading quality of visual and sensory symptoms, they were thought to arise from the cerebral cortex. Motor symptoms previously included as a type of migraine aura were reclassified as a component of hemiplegic migraine. ICHD-3 criteria of the International Headache Society, added brainstem aura and retinal aura as separate subtypes. The susceptibility to all types of aura is likely to be included by complex and perhaps epigenetic factors.
Learn More >To evaluate the frequency and features of onabotulinumtoxinA (onabotA) wear-off in chronic migraine (CM).
Learn More >Opioid misuse and addiction are a public health crisis resulting in debilitation, deaths, and significant social and economic impact. Curbing this crisis requires collaboration among academic, government, and industrial partners towards the development of effective non-addictive pain medications, interventions for opioid overdose, and addiction treatments. A two-day meeting, The Opioid Crisis and the Future of Addiction and Pain Therapeutics: Opportunities, Tools, and Technologies Symposium, was held at the National Institutes of Health to address these concerns and to chart a collaborative path forward. The meeting was supported by the NIH HEAL (Helping to End Addiction Long-term) Initiative, an aggressive, trans-agency effort to speed scientific solutions to stem the national opioid crisis. The event was unique in bringing together two research disciplines, addiction and pain, to create a forum for cross-communication and collaboration. The output from the symposium will be considered by the HEAL Initiative; this article summarizes the scientific presentations and key takeaways. Improved understanding of the etiology of acute and chronic pain will enable the discovery of novel targets and regulatable pain circuits for safe and effective therapeutics, as well as relevant biomarkers to ensure adequate testing in clinical trials. Applications of improved technologies including reagents, assays, model systems, and validated probe compounds will likely increase the delivery of testable hypotheses and therapeutics to enable better health outcomes for patients. The symposium goals were achieved by increasing interdisciplinary collaboration to accelerate solutions for this pressing public health challenge and provide a framework for focused efforts within the research community. SIGNIFICANCE STATEMENT: This article summarizes key messages and discussions resulting from a two-day symposium focused on challenges and opportunities in developing addiction- and pain-related medications. Speakers and attendees came from 40 US states and 15 countries bringing perspectives from academia, industry, government, and healthcare by researchers, clinicians, regulatory experts, and patient advocates.
Learn More >Oncologic breast surgeries carry a risk for persistent postsurgical pain. This study was a randomized pilot and feasibility study of a single-session Acceptance and Commitment Therapy (ACT) intervention compared to treatment as usual among women undergoing surgery for breast cancer or ductal carcinoma in situ (DCIS).
Learn More >Clinical guidelines for the treatment of complex regional pain syndrome recommend multidisciplinary rehabilitation, yet limited evidence exists to support the effectiveness of this approach. Body perception disturbance, a common and debilitating feature of complex regional pain syndrome, is recommended by guidelines as important to treat. However, no study has yet explored whether disturbances change in response to multidisciplinary rehabilitation. We aimed to determine whether there is a change in body perception disturbance and pain following a two-week multidisciplinary rehabilitation program for complex regional pain syndrome.
Learn More >Mindfulness interventions may be beneficial for patients with chronic pain; however, the effects for acute pain are not understood. The purpose of this study was to pilot test a brief mindfulness intervention for acute pain and stress for patients in an inpatient medical setting.
Learn More >Almost 40% of individuals with chronic whiplash-associated disorders (WAD) report headache after 5 years, making it one of the most common persistent symptoms besides neck pain, but randomized treatment studies are lacking. This study aimed to evaluate the effect of 3 different exercise approaches on headache in chronic WAD grades 2 and 3, and to identify potential factors associated with such headache, and whether they differ depending on 3 different aspects of such headache (current headache, maximum headache, or headache bothersomeness).
Learn More >To assess the onset of efficacy for fremanezumab in chronic migraine by evaluating pain-related clinical measures at different time points.
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