NIH HEAL Initiative: National Institute of Neurological Disorders and Stroke Preclinical Program for Non-Addictive Pain Therapeutic Development

Abstract

The National Institutes of Health Helping to End Addiction Long-term, or NIH HEAL Initiative aims to focus efforts on advancing scientific solutions to stem the opioid crisis, improving prevention and treatment of opioid misuse/addiction, and enhancing pain management. NINDS is charged with accelerating the discovery and development of new non-addictive pharmacologic and non-pharmacologic pain therapeutics as part of the HEAL Initiative. PSPP provides researchers from academia and industry, within the US and internationally, an efficient, rigorous, one-stop in vivo resource to screen and profile therapeutic candidates including small molecules, biologics, natural products, and devices for the treatment of pain. Under PSPP direction, preclinical testing is performed by a National Institute of Neurological Disorders and Stroke (NINDS) contract facility, PsychoGenics Inc., in a blinded and confidential manner at no cost to the PSPP participants. Participant assets are evaluated in a suite of in vivo pain-related models, for example, chemotherapy-induced neuropathic pain, osteoarthritis pain, and headache. In these models, PSPP uses both evoked (e.g., paw withdrawal threshold, acetone) and non-evoked (e.g., dynamic weight bearing) endpoints to rigorously assess efficacy of the asset in both male and female animals. Importantly, abuse liability is also assessed using a conditioned place preference paradigm or using intravenous self-administration. A key feature of the PSPP is the flexibility to continuously acquire and validate innovative models and endpoints that more closely represent human pain conditions. Notably, in addition to enabling evaluation of small molecules, biologics and natural products, models and endpoints can be appropriately adapted or incorporated to assess devices. We will describe the advances made to date towards establishing program goals of evaluating assets in a rigorous and reproducible manner.