Overview
The Federal Pain Research Strategy identified an urgent need to reduce reliance on prescription opioid medications through the development of new, non-opioid pharmacologic and non-pharmacologic treatments for pain. This critical need aligns with the goal of the Helping to End Addiction Long-term Initiative®, or NIH HEAL Initiative®, to accelerate the discovery and development of non-addictive pain treatments for the more than 25 million Americans who live with daily chronic pain and rely on opioid medications for pain management. In response, the National Institute of Neurological Disorders and Stroke (NINDS) created the Preclinical Screening Platform for Pain (PSPP) program to identify and profile non-opioid, non-addictive therapeutics for pain.
Eligibility
Researchers from academic institutions, industry, including small businesses, and government institutions (“asset owners”) are eligible to submit novel non-opioid, non-addictive, small molecules, biologics, natural products, or devices (“assets”) for evaluation of efficacy in pain related endpoints. The PSPP Program is not grant-based but operates through a contract mechanism, and there are no set receipt dates. For more information, see “How to Participate” below.
Description of Evaluation
The PSPP program is an efficient, rigorous, one-stop screening resource to accelerate the discovery of effective, non-opioid, non-addictive pain therapies. The PSPP program workflow for the evaluation of assets was established in collaboration with the PSPP External Consultant Board members and based on outcomes from the Critical Evaluation of Animal Pain Models for Therapeutics Development Workshop in January 2019. The preclinical evaluation of accepted assets is performed at no cost to the participant, under NINDS direction by PsychoGenics Inc., confidentially, in a blinded manner. As represented in the figure below, the PSPP program uses a staged approach to evaluate assets. Once an asset is accepted into the program, evaluation of the asset is planned by PSPP, working together with the asset owner. Throughout the evaluation process, PSPP data are reviewed both in the program and with the asset owner before an asset is advanced to the relevant next stage within the program.
- In vitro abuse liability and safety: Initial asset evaluation uses in vitro functional screens of human receptor preparations to determine whether there is activity at opioid receptors, activity at known targets associated with abuse liability, or undesirable off-target activity profiles.
- Pharmacokinetics: Assets may continue into pharmacokinetic studies in Sprague Dawley male and female rats to establish sex-dependent exposure levels and to select an appropriate dose range and timepoints for subsequent behavioral assessments.
- Side effect profile: Assets that advance to the next step are evaluated in a set of validated assays to identify any potential tolerability issues or neurological side effects.
- Efficacy in pain models: The data from all evaluations are then used to set a dose range for the evaluation of efficacy in validated preclinical pain models, including an acute to sub-chronic model (plantar incision) and a chronic/persistent model (L5/L6 spinal nerve ligation). To further characterize the specific pain profile for an asset, the efficacy can also be assessed in disease-specific pain models, such as the MIA model of osteoarthritis or paclitaxel-induced or oxaliplatin-induced peripheral neuropathy. For each pain model, one or more validated endpoints are used to evaluate potential analgesic efficacy of the asset.
- In vivo abuse liability: Finally, assets with demonstrated efficacy can be evaluated for abuse liability in vivo.
Detailed information about each assay, including descriptions of the validated pain models and endpoints can be found on the PSPP Database.
How to Participate
Step 1 : Asset owner requests a meeting
An asset owner interested in learning more about the PSPP program should contact the PSPP Program Director (PD), Smriti Iyengar, cc’ing the PSPP Program Analyst, Lekyla Whitaker, to request a meeting. The e-mail should include a brief description of the project to be discussed. Lekyla Whitaker will work with the asset owner to schedule an introductory meeting.
Step 2 : Introductory meeting with the PSPP program team (confidential)
Participants: asset owner, PSPP program team
Purpose: In this meeting, the asset owner will explain their interest in the PSPP program and rationale for developing their asset for pain, outline the project, target and/or mechanism of action, and current development stage of the asset (~30-45 minutes). The PSPP PD will detail resources available within the program, acceptance criteria, project steps, and anticipated timelines (~10-15 minutes). Both the asset owner and the PSPP program team will have the opportunity to ask any questions in this meeting.
Length: 1 hour
Requirements: The asset owner must send slides to Lekyla Whitaker at least 2 business days prior to the meeting.
Step 3 : Executing the NINDS PSPP Participant Agreement
Upon completion of the introductory meeting, the PSPP program staff will review the asset owner’s project and goals. If the proposed project aligns with the PSPP mission and is stage appropriate, the PSPP PD will ask the asset owner of their interest in moving forward to the NINDS participant agreement step. This participant agreement defines the legal parameters for the partnership, and outlines conditions for confidentiality and intellectual property protection. When the asset owner confirms their interest in moving forward to this step, the PSPP PD will send the participant agreement to the asset owner. When the NINDS PSPP participant agreement is fully signed and executed, the PSPP PD will contact the asset owner to outline the next steps and to schedule a detailed discussion of the project for consideration towards acceptance.
Step 4 : Detailed discussion of the project with NINDS (confidential)
Participants: asset owner, PSPP program team, PSPP SMEs (subject matter experts)
Purpose: The asset owner will present all details and data associated with the project to date, emphasizing the role that PSPP-generated data would have in the overall development of the asset. Information shared in a slide deck should include:
- Chemical structure, physicochemical properties
- Mechanism of action
- In vitro/in vivo pharmacokinetic and/or pharmacodynamic data
- In vivo efficacy data (behavior, electrophysiology, etc.)
- Formulation
- Patent status
- Company information / collaborators
- Other information relevant to planning PSPP assessment
Length: 1 hour
Requirements: The asset owner must send slides to the PSPP Program Analyst Lekyla Whitaker at least 2 business days prior to the meeting.
Following the detailed discussion, the PSPP program team and SMEs will review the project information and determine whether the project meets the PSPP program acceptance criteria, as defined below, and the asset owner will be informed of the program’s decision.
PSPP Program Acceptance
PSPP acceptance criteria
- The project is within scope of the PSPP program, i.e., the asset is non-opioid, non-addictive, and is a strong candidate to treat pain
- Lead candidates are preferred but assets at other stages may be considered
- The data package must be appropriate for the stage of development, and include in vivo efficacy in pain models, if available
- Small molecules and peptides must have > 95% purity
- The asset owner’s development plan indicates that PSPP-generated data will be used to advance development
- PSPP program staff determines that assessment is feasible within the program
Post-acceptance process
- PSPP program staff will work with the asset owner to schedule a meeting to discuss in detail plans for the assessment of the asset within the PSPP program
- The PSPP PD will assign a Scientific Program Manager to be the primary point of contact (POC)
- The asset owner will request credentials for the PSPP online application and will complete registration of the asset within the PSPP online application
- Following review and approval of the registration, the asset owner will ship the asset to RTI International, where it will be blinded and prepared for shipment to the PSPP contract site for evaluation
- RTI will then ship the asset to the PSPP contract site, PsychoGenics Inc.
- Evaluation of the asset will being following the arrival of the asset at PsychoGenics Inc.
Confidentiality
NINDS recognizes the importance of confidentiality to the success of the PSPP program and its participants. A signed PSPP participant agreement is required for consideration of entry into the program. The PSPP participant agreement defines the legal parameters for the partnership and protects the participant’s IP. All screening and other communication activities are performed in strict confidence. Chemical structures are considered proprietary unless otherwise specified by the participant. Evaluation of an asset within the PSPP program is agreed upon by participants in collaboration with PSPP personnel. To further ensure confidentiality and blinding, the PSPP program assigns each newly submitted asset a unique number code to be used in communications, tracking, and analyses. Screening personnel are blinded to both the structure and the source of submitted asset.
PSPP External Guidance
External Consultant Board
The individual members of the Preclinical Screening Platform for Pain (PSPP) External Consultant Board (ECB) provide independent input and oversight on program progress, including strategy and implementation, input on selecting new models, and developing and monitoring screening workflows. As a link to the pain research community, the PSPP ECB helps the program to be more proactive in making adjustments and maintaining relevance as a unique community resource.
Andrew D. Hershey, MD, PhD, FAAN, FAHS, is the director of the Cincinnati Children’s Headache Center and is the Endowed Chair and Director of Neurology and a Professor of Pediatrics and Neurology at the University of Cincinnati, College of Medicine. Prior to joining the University of Cincinnati, Dr. Hershey was a resident in pediatrics, neurology and child neurology at St. Louis Children's Hospital and Barnes-Jewish Hospital, St. Louis, MO. Dr. Hershey's research interests currently include the improved diagnosis and treatment of childhood headache disorders, characterization of outcome responses, studies in new pharmacological and non-pharmacological treatment regimes, and the genomics of migraines.
Jeffrey Kennedy, PhD, is VP of IP and Bioventures at Summer Road, LLC. Previously, Dr. Kennedy was a Senior Fellow (Pain Research) at Eli Lilly and Company and led a behavioral pharmacology group that provided broad support for the pain preclinical portfolio. Prior to Lilly, Dr. Kennedy held a variety of positions of increasing responsibility at Wyeth Pharmaceuticals, including Director of Pain Drug Discovery Research within Neuroscience Discovery. Dr. Kennedy has broad scientific expertise and therapeutic leadership spanning immunology, autoimmunity, pulmonary inflammation, and neuroscience, including pain pathophysiology and neuroinflammation, and has contributed to the therapy development of numerous novel drug candidates.
Steve Negus, PhD, is a Professor in the Department of Pharmacology and Toxicology at Virginia Commonwealth University in 2007. Dr. Negus held positions at the Scripps Research Institute, University of Michigan, and Harvard Medical School before taking on his current position. Dr. Negus has more than 30 years of experience in preclinical assessment of candidate analgesics, preclinical abuse liability testing, and translational research to evaluate candidate medications for treatment of stimulant and opioid abuse. The focus of his research has been in the development and validation of novel preclinical procedures to assess the expression and treatment of pain-related behavioral depression determinants of abuse potential for opioid-analgesics.
Daniela Salvemini, PhD, is Professor and Vice Chair in the Department of Pharmacology and Physiology at Saint Louis University (SLU) School of Medicine. She is also the Director of the SLU Center for Neuroscience and Fellow of the Saint Louis Academy of Science. Dr. Salvemini is a Visiting Professor at the Department of Preclinical and Clinical Pharmacology, University of Florence and is an Adjunct Professor in the Department of Pharmacology, Faculty of Pharmacy of Catanzaro, Italy. Prior to joining SLU, Dr. Salvemini was at Metaphor Pharmaceuticals Inc., where she left as Senior Vice President and had joined from G.D. Searle & Co, where she was Project Leader and led drug discovery efforts on anti-inflammatories and analgesics. Dr. Salvemini uses a multidisciplinary basic science driven translational approach to identify novel non-narcotic analgesics for the treatment of chronic pain as stand-alone or as adjunct to opioids.
Grégory Scherrer, PharmD, PhD, is an Associate Professor at the University of North Carolina (UNC) at Chapel Hill in the Departments of Cell Biology and Physiology, of Pharmacology, and UNC Neuroscience Center. Previously, Dr. Scherrer was Assistant Professor in the Departments of Anesthesiology, Molecular and Cellular Physiology, Stanford University. Dr. Scherrer’s lab investigates the organization of the neural circuits and molecular mechanisms that underlie pain perception and the effects of opioids. Dr. Scherrer’s long-term goal is to develop innovative therapeutics to mitigate opioid side effects and to treat pain more effectively and safely.
Bavani G. Shankar, MBA, is VP, Corporate Operations at BioHaven Pharmaceuticals. Previously she was Head of Transactions, Biopharmaceuticals R&D at AstraZeneca Pharmaceuticals, where she held various roles. Prior to that, she was Vice President, Corporate Development at PsychoGenics Inc. Ms. Shankar’s responsibilities have included identification, evaluation, diligence and transactions on programs for licensing and collaborations across multiple therapeutics areas, including neuroscience and she has also been responsible for leading both preclinical and clinical programs and alliance management.
Ursula Wesselmann, MD, PhD, is a Professor of Anesthesiology, Neurology and Psychology at the University of Alabama at Birmingham (UAB) and holds the William A. Lell, M.D.–Paul N. Samuelson, M.D., Endowed Professorship in Anesthesiology. Previously, Dr. Wesselmann was an Associate Professor in the Department of Neurology, Neurological Surgery and Biomedical Engineering at the Johns Hopkins University School of Medicine after a fellowship there in pain management and prior to that at Massachusetts General Hospital/Harvard Medical School. Dr. Wesselmann’s translational research has focused on the neurobiological mechanisms of chronic pain syndromes and investigating the pathophysiological mechanisms of urogenital and pelvic pain syndromes in women. The long-term goal of her research program is to translate new discoveries into clinical practices that improve the ability to diagnose and treat women experiencing chronic pain.
Resources and Tools
Contacts
For eligibility and participation inquiries, contact:
Smriti Iyengar, PhD | Director, PSPP
smriti.iyengar@nih.gov
Sarah Woller, PhD | Program Director
sarah.woller@nih.gov
Christopher Conrad, PhD | Scientific Program Manager
christopher.conrad2@nih.gov
Lekyla Whitaker, B.S. | Program Analyst
lekyla.whitaker@nih.gov
Accepted PSPP participants, for registration and shipping contact:
Shalini Sharma, M.S. | Scientific Program Manager (Medicinal Chemist)
shalini.sharma@nih.gov
Accepted PSPP participants, for web application support contact:
Dhananjaya Kempegowda (DJ), B.Engr. | Data Scientist Engineer
dhananjaya.kempegowda@nih.gov
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