Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics
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Neuropathic pain is a debilitating form of chronic pain resulting from nerve injury, disease states, or toxic insults. Neuropathic pain is often refractory to conventional pharmacotherapies, necessitating validation of novel analgesics. Cannabinoids, drugs that share the same target as Delta(9)-tetrahydrocannabinol (Delta(9)-THC), the psychoactive ingredient in cannabis, have the potential to address this unmet need. ⋯ Clinical studies largely affirm that neuropathic pain patients derive benefits from cannabinoid treatment. Subjective (i.e., rating scales) and objective (i.e., stimulus-evoked) measures of pain and quality of life are considered. Finally, limitations of cannabinoid pharmacotherapies are discussed together with directions for future research.
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This review examines recent preclinical research on toxic peripheral neuropathy and potential therapeutic developments. Chemotherapy-induced peripheral neurotoxicity is a major clinical problem because it represents the dose-limiting side effects of a significant number of antineoplastic drugs. Patients are unable to complete full or optimal treatment schedules. ⋯ As such, improved understanding of the pathophysiology of chemotherapy-induced neurotoxicity need for animal models is clinically relevant and will assist in the development of future neuroprotective strategies and also in the design of novel chemotherapies with improved toxicity profiles. In this review, the features of animal models of chemotherapy-induced painful neuropathy developed for 20 years, due to the administration of the most widely used drugs, such as platinum drugs, taxanes, and vinca alkaloids, will be discussed. In a second part, data available on neuroprotectants and treatment strategies, evaluated using these previous animal models in the attempt to prevent neuropathic pain, will be summarized.
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The translation of analgesic efficacy seen in preclinical pain models into the clinic is problematic and is associated with a number of factors that may result in the failure of clinical trials to detect the effect of investigational therapeutic agents. The use of translational pain biomarkers in phase I trials can potentially reduce some of these risks by measuring the interaction between the drug and its target (termed target engagement) in humans. ⋯ Here we discuss some examples to assess the utility of sensory and related pain biomarkers in the early phase of evaluation of novel analgesics for confirmation of target engagement in humans. The emphasis is on the TRPV1 antagonists, but some other target mechanisms are also discussed in examining the validity of this approach.
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Classification of neuropathic pain has been based on disease entities, anatomical localization, or histological observations. Over the past decade, there has been an explosion in our understanding of the basic mechanisms of neuropathic pain. The exciting advances in basic science are paralleled by the recognition from clinical investigations that neuropathic pain is not a monolithic entity, but instead presents as a composite of pain and other sensory symptoms. ⋯ First, in clinical proof-of-concept trials the study population can be enriched prospectively on the basis of entry criteria defined a priori. This enrichment with patients who potentially require a specific treatment should increase the likelihood for positive trial outcomes. Second, in clinical practice it becomes possible to establish an individualized therapy--that is, to identify the particular patients who require a specific treatment option.