# Thalamocortical dynamics during nociception and endogenous analgesia

> **NIH NIH F99** · UNIVERSITY OF PENNSYLVANIA · 2024 · $49,974

## Abstract

Project Summary
Ineffective pain management is an urgent medical crisis impacting the lives of over 50 million Americans
and millions more chronic pain patients around the world. Opiate analgesics can provide robust pain relief but
can also produce life-threatening side effects and high rates of misuse, which contributes to the ongoing
Opioid Epidemic. Unlike the off-target effects of opiates that act widely throughout the body to indiscriminately
bind mu-opioid receptors (MOR) on many cell-types, endogenous opioid peptides mediating
antinociception undergo controlled release at specific synapses from specific nociception-related cell-types.
Identifying the precise noci-ceptive cell-types that express MORs, which are regulated by endogenous opioids,
may lead to new research developments for effective circuit-targeted analgesic treatments to minimize the
need for traditional opiate anal-gesics and reduce abuse liabilities. The rostral intralaminar thalamus {rlLN) is
critical in this regard as it is known to relay nociceptive information from spinal cord and brainstem structures
to cortical regions, such as the rostral anterior cingulate cortex (rACC). rlLN neurons express high densities of
MORs {rlLNMOR), yet it remains unknown whether endogenous forms of pain relief modulate nociceptive
activity within this rlLNMOR ➔ rACC circuit. To enhance our investigations into thalamocortical circuits in
endogenous analgesia processes, we have developed an operant conditioning assay that leverages
expectation-induced antinociception, i.e. placebo analgesia, in a drug-free manner. The F99 phase entails two
subaims. In Aim 1a, the applicant will leverage in vivo fiber photometry calcium imaging to determine
nociception and analgesia-related responses in the axonal projections of rlLNMOR ➔ rACC. In Aim 1b, to
determine the necessity of MOR signaling in thalamocortical neurons for the endogenous analgesia response,
the applicant will use an intersectional genetic and viral approach to selectively delete MORs from rlLN ➔ rACC
neurons. The KOO phase, Aim 2, will help prepare the applicant for a successful academic research career
investigating neurobiological mechanisms of gastrointestinal pain. This postdoctoral period will provide the
applicant with expertise in techniques like 2-photon calcium imaging of neural population dynamics in the brain
during visceral pain models, as well as sharpen managerial and mentoring skills necessary to succeed and
thrive as an independent research scientist. In total, successful completion of this proposal will provide insight
into neurobiological mechanisms underlying pain and analgesia, while also equipping the applicant, Lindsay
Ejoh, to uncover brain circuit mechanisms of severe and chronic gastrointestinal pain disorders under her own
independent research program.

## Key facts

- **NIH application ID:** 11000645
- **Project number:** 1F99NS135765-01A1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Lindsay Ejoh
- **Activity code:** F99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $49,974
- **Award type:** 1
- **Project period:** 2024-07-08 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11000645

## Citation

> US National Institutes of Health, RePORTER application 11000645, Thalamocortical dynamics during nociception and endogenous analgesia (1F99NS135765-01A1). Retrieved via AI Analytics 2026-06-16 from https://api.ai-analytics.org/grant/nih/11000645. Licensed CC0.

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