Concept: Natural Products and Pain Concept Clearance

Project Concept Review

Council Date: June 7, 2019

Program Officer: D. Craig Hopp, Ph.D.

Background

In light of the ongoing opioid epidemic, discovery of new nonaddictive pain treatments is of the highest importance. Nature has been a prolific source of analgesic compounds. Much of what we know about nociception is due to discovery of natural products that illuminated the various signaling pathways and targets responsible for sensory perception of painful stimuli. Yet despite this history, there is very limited current research devoted to discovering new natural products with analgesic activity. Thus, a renewed focus on studying natural products for pain management seems not only timely but also perhaps the most productive approach to take in our quest for solutions to the current opioid crisis.

The National Center for Complementary and Integrative Health (NCCIH) interest in natural products and pain is closely related to the Helping to End Addiction Long-term^® Initiative, or NIH HEAL Initiative^®,  that has become a landmark research effort at the National Institutes of Health (NIH). HEAL includes numerous initiatives aimed at improving prevention and treatment for opioid misuse and addiction as well as enhancing pain management. For pain management, these efforts span from early-phase discovery and preclinical development to advancing treatments through the clinical pipeline.

In February 2019, a workshop titled “Natural Products and Pain: The Search for Novel Nonopioid Analgesics” was organized collaboratively by NCCIH, the National Center for Advancing Translational Sciences, and the National Institute of Neurological Disorders and Stroke. Speakers from across academia, industry, and Government sectors gathered to discuss ongoing efforts related to natural products and pain. The goal of that workshop was to explore the current state of research on analgesic compounds from across all natural product sources in an effort to identify novel nonopioid natural products with efficacious and nonaddictive analgesic properties. Additionally, there was discussion of research barriers for the study of such natural products for pain treatment and management. Participants at the workshop identified several key research gaps and opportunities, especially related to resource development and early-phase discovery efforts.

Purpose of Proposed Program

NCCIH wishes to develop a coordinated platform of activities that will increase discovery of novel nonaddictive analgesic natural products while also leveraging existing HEAL efforts at NIH for translational research on natural products and pain. These efforts would start with increasing the knowledge base regarding existing literature on natural products and pain, particularly associated with traditional medicine practices from around the world. This should provide a valuable resource for researchers that will offer abundant opportunities for discovery of new analgesic natural products. The next phase of this platform would include support for screening activities that leverage, where possible, existing resources from either currently available natural product libraries or ongoing screening efforts. These screening efforts are expected to yield promising natural product leads. The last phase seeks to better integrate natural products research into ongoing HEAL efforts that support target validation, preclinical Investigational New Drug application (IND)-enabling research, and clinical trials on new nonaddictive pain management treatments.

Objectives

Successful achievement of these objectives will require careful coordination with many stakeholders. It is anticipated that multiple activities could be ongoing in parallel addressing the three phases described. This is expected to be a collaborative effort that may include not only other NIH partners, but potentially industry and nonprofit groups as well. Examples of activities that could be supported through this concept include, but are not limited to:

• Mining of existing literature and other resources to compile a robust list of understudied natural products with evidence of analgesic activity.
• Collection of plants and/or other natural product sources from around the world with reported analgesic activity that are not available in existing natural product repositories.
• High-throughput screening of natural product libraries with established pain targets or phenotypic assays, especially those leveraging existing natural product repositories and ongoing NIH screening infrastructure.
• Discovery and identification of natural products with promising analgesic activity.
• Leveraging ongoing HEAL initiatives as potential avenues for translational development of promising nonaddictive analgesic natural products.