Northwestern University, Chicago, Illinois, United Statesīackground: Decline in memory function during normal aging is one of the major causes of disability. Keywords: Pain, Preclinical Models and Endpoints, Validation, Heal Initiativeĭisclosure: Electrical Engineering, Delphi: Employee (Spouse), Eli Lilly: Retiree, Stock / Equity (Self) Advances in understanding these endpoints and representative data will be presented.Ĭonclusions: This presentation will describe efforts to standardize models and endpoints to enhance rigor and reproducibility while evaluating potential non-opioid, non-addictive therapeutics for pain within the NINDS HEAL Initiative PSPP program. Another exciting feature of the program that will be highlighted in this presentation will be assessment of abuse liability in the context of efficacy in pain endpoints. For example, we aim to understand whether endpoints such as gait, wheel running, guarding, place escape avoidance paradigm (PEAP), and electroencephalogram (EEG) are useful endpoints in a model of nerve injury. This includes validation of models of nerve injury, chemotherapy-induced neuropathic pain, post-operative pain, pain associated with osteoarthritis, deep muscle pain, and migraine, as well as validation of existing endpoints, of evoked pain measures but more importantly, validating non-evoked endpoints for use in these models. In collaboration with key opinion leaders in the field, NINDS and PsychoGenics have been validating existing preclinical models of pain in rodents for inclusion in the PSPP workflow. Results: A key component of the PSPP is to validate new and existing models and endpoints. All experiments are blinded, both sexes are included, group sizes are determined by power analysis, and data are reported in accordance with ARRIVE guidelines
In vivo pharmacokinetic studies are then used to measure plasma and brain exposures to guide the dose range and pretreatment times for the side effect profile, in vivo efficacy, and in vivo abuse liability studies. Assets are evaluated in a tiered manner, starting with in vitro functional assays to rule out opioid receptor activity and to assess in vitro abuse liability. Methods: The PSPP aims to screen and profile candidate therapeutics in a number of preclinical assays. PSPP is working with PsychoGenics to develop and validate preclinical models and endpoints to enable the screening and profiling of assets, including small molecules, biologics, natural products, and devices. Toward this goal, NINDS created the Preclinical Screening Platform for Pain (PSPP) with the aim of accelerating the preclinical development of non-opioid, non-addictive therapeutics for pain. As part of the NIH HEAL Initiative, the National Institute of Neurological Disorders and Stroke (NINDS) has been charged with enhancing pain management and accelerating the discovery and development of new non-addictive pain therapeutics.
NINDS/NIH, Carmel, Indiana, United Statesīackground: The NIH Helping to End Addiction Long-term Initiative, or NIH HEAL Initiative, is a trans-agency effort to provide scientific solutions to the opioid crisis.
0 kommentar(er)
