With NIH HEAL (Helping to End Addiction Long-term) Initiative support, NINDS is developing a Preclinical Screening Platform for Pain (PSPP) program to facilitate the identification of potential non-addictive treatments (small molecules, biologics, devices, or natural products) for acute and chronic pain conditions. Under NINDS direction, preclinical testing of submitted agents is performed by contract facilities on a blinded and confidential basis and at no cost to the PSPP participants. NINDS PSPP staff report test results to participants and provide advice on next steps for promising agents.
The overall goal of the PSPP is to provide pain researchers from the academic and industry community with an efficient, rigorous one-stop in vivo screening resource to accelerate efficacy profiling and identification of alternatives to opioid analgesics. PSPP conducts an assessment of in vitro and pharmacokinetic profiles, side effect profiles, abuse liability, and efficacy in models relevant to human pain conditions.
More than 25 million Americans live with daily chronic pain and lack effective and safe non-opioid options for pain management. The Federal Pain Research Strategy, published in 2017, strongly supported the development of safer new, non-opioid analgesics. Research offered by the PSPP will be a key step in transitioning HEAL preclinical programs into clinical programs, directly aligned with the HEAL Initiative goal of “accelerating the discovery and pre-clinical development of non-addictive pain treatments.”
Description of Testing Services
Evaluation of a submitted compound for suitability for testing in the PSPP begins with an assessment of the proposed scientific rationale. Accepted agents are evaluated in assays whose sequence is described in specific flow charts. Each stage of evaluation occurs with NINDS PSPP staff consultation with the participant. The PSPP provides the participant with feedback on results and recommends next steps in the process.
How to Participate
PSPP is now accepting compounds for evaluation continuously on an ongoing basis. Researchers from academic, industry, U.S., and abroad are eligible to submit compounds for screening. A signed confidentiality agreement between the NINDS and each potential participant is required before submission of compounds for evaluation.
To start the process those interested in participating should contact Smriti Iyengar, Ph.D. for more information and to discuss research goals, resources, and timelines. For compounds approved for testing in the program, initial evaluation is normally performed using in vitro assays and rat pharmacokinetic studies. The amount of compound required for subsequent testing in pain models will vary depending on the expected dose range. Directions for packaging and compound submission are provided prior to sample shipment.
NINDS recognizes the importance of confidentiality to the success of the PSPP and its participants. Participation in the PSPP begins only after the appropriate representatives from both the participant's organization and the NINDS sign the participant agreement. This document defines the legal parameters for the partnership. All screening and other communication activities are performed in strict confidence to allow the participant to retain intellectual property. Chemical structures are considered proprietary unless otherwise specified by the supplier. The only testing undertaken by the PSPP is that agreed upon by participants in collaboration with PSPP personnel. To further assure confidentiality, each newly submitted compound is assigned a unique PSPP number code to be used in communications, tracking, and analysis. Screening personnel are blinded to both the structure and the source of submitted compounds, and screening results are provided exclusively to the participating supplier unless otherwise authorized.
External Consultant Board
The individual members of the Preclinical Screening Platform for Pain (PSPP) External Consultant Board (ECB) will provide independent input and oversight on strategy and implementation, including input on selecting new models, developing and monitoring screening flows, prioritizing targets and mechanisms for interrogation, and establishing milestones for program progress. As a link to the pain research community, the ECB will help the program to be more proactive in making adjustments and maintaining relevance as a unique community resource. The membership of this group should allow for some consistency over time as well as for ad hoc participation of individuals with expertise appropriate for specific programmatic matters. Learn More
Connections to Other HEAL Initiative Programs
This platform will be an open-access resource to any investigator with a promising non-addictive therapeutic for pain. Investigators who successfully complete basic science projects through the programs for Discover and Validate Novel Targets for Safe and Effective Pain Treatment (RFA-NS-18-042, RFA-NS-18-043, NOT-NS-18-073) are encouraged to submit their candidate therapeutics for testing to the PSPP so that they can be tested for “generalizability” amongst models of different pain conditions and ensure that each therapeutic has low abuse liability and is supported by rigorous, high quality data.
The National Center for Advancing Translational Sciences has also established a complementary in vitro screening platform for testing of therapeutic candidates.
Therapeutics that successfully ‘graduate’ from the PSPP (i.e., are shown to be effective in preclinical models of pain lacking addiction liability) will be better-positioned to benefit from other funding opportunities and utilize other resources provided by NINDS and NCATS through the Optimization of Non-addictive Therapies [Small Molecules and Biologics] to Treat Pain opportunities (RFA-NS-19-010) and through the Early Phase Pain Investigation Clinical Network (EPPIC-Net) for clinical trials.
Resources and Tools
The ETSP is an NINDS-funded screening program for identifying new treatments for epilepsy which provides the concept for the PSPP.