Epigenomic regulation of long term gene expression plays a critical role in neuroplastic processes such as addiction, learning, and memory. Epigenomic processes could also play a role in the transition from acute to chronic pain and the maintenance of a chronic pain state. Although the roles of epigenomic or non-coding RNA processes in pain are not well understood, an appreciation for their importance is emerging. Indeed, histone deacetylase inhibitors (HDACis) have been shown to reduce inflammatory sensitivity to pain, while they also have been shown to increase C fiber sensitivity in a neuropathic pain model. Similarly, peripheral nerve injury has been associated with an increase in expression of DNA methyltransferase 3a, methylation of a potassium channel (Kcna2) promoter, and increased neuropathic pain. It should be noted that epigenomic regulators have evolved specifically to bind to small molecules and thus may provide useful targets for the development of new pain therapeutics.
The purpose of this initiative is to encourage research that investigates the role of epigenetic or non-coding RNA regulatory pathways in the development, perdurance, or treatment of chronic pain. Proposed projects submitted to this FOA should have the following characteristics:
- The major thrust should investigate cells or tissues from human pain patients and controls or from well-justified animal models of inflammatory or neuropathic pain. Researchers may wish to exploit the interesting differences in the development and maintenance of chronic pain in males and females. Given the complex nature of chronic pain, a wide variety of cell or tissue types could be studied including central nervous system, spinal cord, peripheral neurons, microglia, or specific immune cell types. Researchers may propose analysis of multiple single cells, purified populations of cells, or tissues. However, investigations focused solely on a complex mixture of blood cell types (e.g. whole blood) are not of interest.
- The major thrust should also investigate one or more epigenomic and/or non-coding RNA mechanisms involved in gene expression regulation. These mechanisms might include small or long non-coding RNAs, histone modifications, histone isoforms, DNA or RNA modifications, nucleosome remodeling, or higher order chromatin structure. Applicants are expected to measure gene expression levels and may propose to investigate how specific transcription factors interface with the above regulatory processes.
Applicants should also include aims or sub-aims that address at least one of the two NIH Institute/Center-specific interests noted below
- NIDA interest statement. The high rate of chronic pain in the US has contributed in part to the current opioid epidemic. NIDA is interested in applications that propose to understand how chronic pain regulatory pathways interact either with molecular pathways involved in opioid use disorder (OUD) or with molecular pathways involved in opioid induced hyperalgesia (OIH).
- NCCIH interest statement. NCCIH supports research on the science and clinical applications of complementary and integrative health approaches in chronic pain management and their contributions to reduce the current opioid epidemic. NCCIH is interested in applications that explore the mechanisms by which natural products (including botanicals, probiotics, dietary supplements, and special diets) and mind and body approaches (such as acupuncture, meditation, spinal manipulation, yoga, massage, hypnosis) modulate epigenomic processes, non-coding RNA regulation, and related gene expression in association with the regulation of chronic pain and treatment responses.
Other Application Considerations:
- The R61/R33 grant mechanism includes an exploratory high risk/high pay off R61 phase (two years). Preliminary data are not required; however, applicants may include preliminary data if they are available. Given the high risk/high pay off nature of this funding opportunity, applicants are encouraged to present a well-designed research plan that addresses appropriate scientific controls, pitfalls, and alternative approaches.
- Near the end of the R61 phase, NIH scientific staff will review progress made towards the proposed R61 milestones and recommend a subset of R61 projects for continued support through the R33 phase (three years) pending merit and the availability of funds. Applicants must propose both an R61 and an R33 phase.
- As a part of designing the proposed research project,applicants are expected to develop and describe quantitative milestones (perhaps in the context of a timeline) that they anticipate achieving during the R61 phase and would justify further support during an R33 phase.
- Clinical trials with clinical measures as the primary outcomes will NOT be supported by this initiative.
- Applications from interdisciplinary teams are encouraged.
Deadlines: July 17, 2018, November 13, 2018 February 11, 2019, July 17, 2019, November 13, 2019, February 11, 2020, July 17, 2020, November 13, 2020, February 11, 2021
Filed Under: Funding Opportunities