# Determining the functions of molecularly defined populations of nociceptors in spinal and dental pain

> **NIH NIH R00** · UNIVERSITY OF PENNSYLVANIA · 2020 · $290,717

## Abstract

Project Summary/Abstract
Chronic pain of the body and orofacial region represents a major health burden and the neural circuit
mechanisms underlying long-lasting pain remain largely unknown. The current treatment options for pain are
largely non-specific, have unwanted side effects, poor efficacy in many patients, and some have abuse
potential. Therefore, the need to design more targeted therapies is imperative and to accomplish this,
knowledge of the neural circuits responsible for pain is critical. The long-term objectives of this research are to
define neural circuit mechanisms responsible for chronic pain, particularly in the orofacial region. The principal
investigator has made use of a new mouse line in which he can target blue-light sensitive ion channels to
molecular populations of nociceptors and optogenetically activate them in vivo. His preliminary data shows that
he can trigger long-lasting spontaneous pain with this novel and non-invasive technique. He has also shown
that he can use similar technologies with the Cre-lox system to ablate molecularly defined populations of
nociceptors to investigate their functions in pain. In Aim 1 of the K99 mentored phase he will use optogenetics
coupled with animal behavior and electrophysiology to uncover neural circuit mechanisms important for the
transition from acute to chronic pain. In Aim 2 of the K99 mentored phase he will use a tooth pulp injury model
with an apparatus to measure orofacial pain coupled with ablation or activation of a molecularly defined
population of nociceptors to determine their functions in dental pain. Lastly, during the R00 independent phase
in Aim 3, the principal investigator will use the the same tooth pulp injury model together with the skills and
techniques acquired during the mentored phase to investigate two additional populations of nociceptors that
may be involved in sensitivity to thermal stimuli following dental pulp injury. Completion of the three listed aims
will make him proficient in using mouse molecular genetics to control the activity of nociceptors while
investigating their functions in dental pain. The principal investigator will learn the skills and new techniques
necessary to accomplish the proposed research under the guidance of his mentoring team (Drs. Brian
Schmidt, Wenqin Luo, Minghong Ma, Michael Nusbaum, and Jonathan Raper) and his consultants (Drs. Elliot
Hersh, and Syngcuk Kim, and Yuanxiang Tao), who have pioneering expertise in using the listed methods and
models. Importantly, his mentoring committee collectively has a very strong track record of training
postdoctoral fellows in transitioning into independent investigators. He will also engage in seminars and take
coursework on modern neuroscience techniques, grant writing, bioethics training, and training on running a
laboratory. Combining the new skills learned during the K99 mentored phase with his prior expertise in
molecular biology and mouse genetic targeting, will ensure a strong...

## Key facts

- **NIH application ID:** 9980200
- **Project number:** 5R00DE026807-04
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Ishmail John Abdus-Saboor
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $290,717
- **Award type:** 5
- **Project period:** 2018-08-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9980200

## Citation

> US National Institutes of Health, RePORTER application 9980200, Determining the functions of molecularly defined populations of nociceptors in spinal and dental pain (5R00DE026807-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9980200. Licensed CC0.

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