Methods in molecular biology
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Spinal cord injury-induced pain is a common clinical problem affecting adversely the quality of daily lives of spinal cord injured patients. Management with current pain medications can only lead to partial pain relief in some spinal cord injured patients, which is usually associated with unfavorable side effects. ⋯ We describe here the generation of a spinal cord contusion injury model that mimics the etiology and phenotypes of chronic pain states in spinal cord injured patients. Therefore, this model can be a useful tool for studying spinal cord injury mechanisms, functional recovery, research, and development of new medications for better functional and symptomatic improvements, including pain management.
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Central neuropathic pain is associated with many disease states including multiple sclerosis, stroke, and spinal cord injury, and is poorly managed. One type of central neuropathic pain that is particularly debilitating and challenging to treat is pain that occurs below the level of injury (below-level pain). The study of central neuropathic pain is commonly performed using animal models of stroke and spinal cord injury. ⋯ The second was developed to accommodate intrathecal application of pharmacological manipulations. This model provides an additional means by which to investigate central pain states associated with spinal cord injury, including below-level pain. Finally, a brief discussion of at-level pain measurement is described as it has been suggested in the literature that the mechanisms underlying below- and at-level pain are different.
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Developments in psychoneuroimmunology (PNI) need to be translated into personalized medicine to achieve better clinical outcomes. One of the most critical steps in this translational process is to identify systemic biomarkers for better diagnosis and treatment. Applications of systems biology approaches in PNI would enable the insights into the correlations among various systems and different levels for the identification of the basic elements of the psychophysiological framework. ⋯ The understanding of the general systemic pathways among different disorders may contribute to the transition from the disease-centered medicine to patient-centered medicine. Integrative strategies targeting these factors and pathways would be useful for the prevention and treatment of a spectrum of diseases that share the common links. Examples of the translational implications of potential PNI biomarkers and networks in diseases including depression, Alzheimer's disease, obesity, cardiovascular disease, stroke, and HIV are discussed in details.
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The spared nerve injury (SNI) model mimics human neuropathic pain related to peripheral nerve injury and is based upon an invasive but simple surgical procedure. Since its first description in 2000, it has displayed a remarkable development. ⋯ Besides, variants of the SNI model have been developed in rats, mice and neonatal/young rodents, resulting in several possible angles of analysis. Therefore, the purpose of this chapter is to provide a detailed guidance regarding the SNI model and its variants, highlighting its surgical and behavioural testing specificities.
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Computational methods now play an integral role in modern drug discovery, and include the design and management of small molecule libraries, initial hit identification through virtual screening, optimization of the affinity and selectivity of hits, and improving the physicochemical properties of the lead compounds. In this chapter, we survey the most important data sources for the discovery of new molecular entities, and discuss the key considerations and guidelines for virtual chemical library design.