# Function of the Parabrachial Nucleus to Central Amydala Pathway in Pain-Related Plasticity

> **NIH NIH FI2** · U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES--NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RES · 2020 · —

## Abstract

PROJECT SUMMARY
 The annual national health cost for chronic pain conditions ranges between 560 to 635 billion dollars,
which is higher than the combined costs for cancer, diabetes, and cardiovascular diseases. Chronic pain patients
live with a lower quality of life that is further aggravated by patients’ frequent comorbidities with mental health
disorders and substance abuse problems. Despite being a significant health concern, the biological mechanisms
underlying chronic pain conditions have not been completely identified. Recently, the central amygdala (CeA)
has been identified as an important center for pain modulation, with a dual function on pain perception through
the activity of two separate cell populations: pain-promoting (pronociceptive) protein kinase c delta-expressing
cells (CeA-PKCδ+) and antinociceptive somatostatin-expressing cells. The purpose of this research proposal is
to further understand the circuit mechanisms underlying those findings by studying the synaptic connectivity
changes behind CeA-PKCδ+ cells pronociceptive function. The central hypothesis of this proposal is that
selective strengthening of nociceptive inputs to CeA-PKCδ+ neurons underlies behavioral hypersensitivity
following injury. It is known that nociceptive information is conveyed to the CeA by projections sent from the
lateral parabrachial nucleus (LPB), a pontine structure critical for pain-related information processing. Therefore,
this proposal will test whether injury-related potentiation of the LPB to CeA pathway is specific to CeA-PKCδ+
neurons, whether this potentiation drives pain-related behavioral hypersensitivity, and whether this potentiation
is necessary for injury-induced behavioral hypersensitivity. In Aim 1, the preliminary data showing injury-induced
potentiation of excitatory synaptic transmission onto CeA-PKCδ+ neurons will be further investigated by
dissecting the function of excitatory LPB inputs using ex vivo optogenetically-assisted circuit mapping. In Aim 2,
the in vivo dynamics of the LPB to CeA pathway in freely behaving animals in terms of CeA-PKCδ+ neuronal
activity and pain-related behavioral hypersensitivity will be established. Furthermore, the goal in Aim 3 is to
establish a causal link between LPB to CeA pathway function, pain-related behaviors, and CeA-PKCδ+ cells
neuronal activation. The experiments of Aim 1 will provide the trainee the opportunity to improve his current ex
vivo electrophysiological skills. The experiments of Aims 2 and 3 will provide the trainee the opportunity to receive
training in cutting-edge in vivo neurocircuitry tools to complete the experiments proposed and to address the
biological questions in these aims. The findings obtained from the proposed research will expand our
understanding of how the brain modulates pain, which might ultimately lead to the identification of better
treatment options for individuals suffering from chronic pain conditions.

## Key facts

- **NIH application ID:** 10027489
- **Project number:** 1FI2GM138065-01
- **Recipient organization:** U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES--NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RES
- **Principal Investigator:** Omar Soler-Cedeno
- **Activity code:** FI2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2020-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10027489

## Citation

> US National Institutes of Health, RePORTER application 10027489, Function of the Parabrachial Nucleus to Central Amydala Pathway in Pain-Related Plasticity (1FI2GM138065-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10027489. Licensed CC0.

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