Neuroplasticity can be defined as the ability of the nervous system to respond to intrinsic or extrinsic stimuli by reorganizing its structure, function and connections. Major advances in the understanding of neuroplasticity have to date yielded few established interventions. To advance the translation of neuroplasticity research towards clinical applications, the National Institutes of Health Blueprint for Neuroscience Research sponsored a workshop in 2009. Basic and clinical researchers in disciplines from central nervous system injury/stroke, mental/addictive disorders, paediatric/developmental disorders and neurodegeneration/ageing identified cardinal examples of neuroplasticity, underlying mechanisms, therapeutic implications and common denominators. Promising therapies that may enhance training-induced cognitive and motor learning, such as brain stimulation and neuropharmacological interventions, were identified, along with questions of how best to use this body of information to reduce human disability. Improved understanding of adaptive mechanisms at every level, from molecules to synapses, to networks, to behaviour, can be gained from iterative collaborations between basic and clinical researchers. Lessons can be gleaned from studying fields related to plasticity, such as development, critical periods, learning and response to disease. Improved means of assessing neuroplasticity in humans, including biomarkers for predicting and monitoring treatment response, are needed. Neuroplasticity occurs with many variations, in many forms, and in many contexts. However, common themes in plasticity that emerge across diverse central nervous system conditions include experience dependence, time sensitivity and the importance of motivation and attention. Integration of information across disciplines should enhance opportunities for the translation of neuroplasticity and circuit retraining research into effective clinical therapies.
Interoception refers to the representation of the internal world, and includes the processes by which an organism senses, interprets, integrates, and regulates signals from within itself.The brain communicates with internal organs via the peripheral nervous system and non-neuronal systems.
In addition to greater cross-disciplinary research, there is a need for new approaches to training clinicians and investigators, which integrate concepts and methodologies from individual disciplines, focus on emerging methodologies, and prepare investigators to assess complex, multisystem associations.
Objective There has been a growing recognition of the need for better pharmacologic management of chronic pain among older adults. To address this need, the National Institutes of Health Pain Consortium sponsored an “Expert Panel Discussion on the Pharmacological Management of Chronic Pain in Older Adults” conference in September, 2010, to identify research gaps and strategies to address them. Specific emphasis was placed on ascertaining gaps regarding use of opioid and non-steroidal anti-inflammatory medications because of continued uncertainties regarding their risks and benefits. Design Eighteen panel members provided oral presentations; each was followed by a multidisciplinary panel discussion. Meeting transcripts and panelists’ slide presentations were reviewed to identify the gaps, and the types of studies and research methods panelists suggested could best address them. Results Fifteen gaps were identified in the areas of treatment(e.g., uncertainty regarding the long-term safety and efficacy of commonly prescribed analgesics), epidemiology (e.g., lack of knowledge regarding the course of common pain syndromes), and implementation(e.g., limited understanding of optimal strategies to translate evidence-based pain treatments into practice). Analyses of data from electronic health care databases, observational cohort studies, and ongoing cohort studies (augmented with pain and other relevant outcomes measures) were felt to be practical methods for building an age-appropriate evidence base to improve the pharmacologic management of pain in later life. Conclusions Addressing the gaps presented in the current report was judged by the panel to have substantial potential to improve the health and well being of older adults with chronic pain.
CNS is a major player in the process, leading to mobility decline with aging. Future research in this area has the potential to prolong independence in older persons. Better interactions among disciplines and shared research paradigms are needed to make progress. Research priorities include the development of innovative approaches to integrate research on aging, cognition, and movement with attention to neurovascular function, neuroplasticity, and neurophysiological reserve.
Use of opioid analgesics for pain management has increased dramatically over the past decade, with corresponding increases in negative sequelae including overdose and death. There is currently no well-validated objective means of accurately identifying patients likely to experience good analgesia with low side effects and abuse risk prior to initiating opioid therapy. This paper discusses the concept of data-based personalized prescribing of opioid analgesics as a means to achieve this goal. Strengths, weaknesses, and potential synergism of traditional randomized placebo-controlled trial (RCT) and practice-based evidence (PBE) methodologies as means to acquire the clinical data necessary to develop validated personalized analgesic prescribing algorithms are overviewed. Several predictive factors that might be incorporated into such algorithms are briefly discussed, including genetic factors, differences in brain structure and function, differences in neurotransmitter pathways, and patient phenotypic variables such as negative affect, sex, and pain sensitivity. Currently available research is insufficient to inform development of quantitative analgesic prescribing algorithms. However, responder subtype analyses made practical by the large numbers of chronic pain patients in proposed collaborative PBE pain registries, in conjunction with follow-up validation RCTs, may eventually permit development of clinically useful analgesic prescribing algorithms. Perspective Current research is insufficient to base opioid analgesic prescribing on patient characteristics. Collaborative PBE studies in large, diverse pain patient samples in conjunction with follow-up RCTs may permit development of quantitative analgesic prescribing algorithms which could optimize opioid analgesic effectiveness, and mitigate risks of opioid-related abuse and mortality.
Protein phosphorylation events are key regulators of cellular signaling processes. In the era of functional genomics, rational drug design programs demand large-scale high-throughput analysis of signal transduction cascades. Significant improvements in the area of mass spectrometry-based proteomics have provided exciting opportunities for rapid progress toward global protein phosphorylation analysis. This review summarizes several recent advances made in the field of phosphoproteomics with an emphasis placed on mass spectrometry instrumentation, enrichment methods and quantification strategies. In the near future, these technologies will provide a tool that can be used for quantitative investigation of signal transduction pathways to generate new insights into biologic systems.
In order to develop effective preventive interventions for this prevalent syndrome, multidisciplinary teams are essential particularly because of the complex nature of the syndrome. Additionally, integrating innovative methods into the design of interventions may help researchers better measure complex mechanisms, and finally, the value of understanding the link between the CNS and mobility should be conveyed to researchers across disciplines in order to incorporate cognitive and mobility measurements into study protocols.
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