# Amygdala pain mechanisms

> **NIH NIH R01** · TEXAS TECH UNIVERSITY HEALTH SCIS CENTER · 2020 · $334,688

## Abstract

Project Summary
Chronic pain remains a major health care issue and presents a therapeutic challenge. A complex disorder with
different dimensions, pain involves and affects neural function at various levels. And so it is not surprising that
chronic pain mechanisms are still not well understood. To address this important knowledge gap we will build
on our NIH-funded work (since 1999) that impacted the field by identifying neuroplasticity in the amygdala, a
brain center for emotions, as a key mechanism for emotional-affective aspects of pain and pain modulation
(Neugebauer, 2015). Control of amygdala activity has emerged as a desirable therapeutic goal (see Simons et
al., 2014;Baliki and Apkarian, 2015), but mechanisms of abnormal excitability and amygdala output in chronic
pain remain poorly understood. The proposed project will test the novel hypothesis that loss of function of
small conductance calcium-activated potassium (SK) channels is a critical mechanism of uncontrolled
amygdala output in neuropathic pain, which allows the abnormal persistence of pain behaviors but can
be mitigated with a gene transfer based rescue strategy (AAV-mediated SK2 expression). SK channels
are important regulators of neuronal excitability and hold promise as targets for neuropsychiatric and
neurodegenerative disorders. More recently, they have also been implicated in the regulation of peripheral and
spinal nociceptive processing. Role, regulation and therapeutic potential of SK channels in pain-related brain
functions and plasticity are unknown, and the concept of SK channel dysfunction as a pain mechanism is
novel. A comprehensive multidisciplinary approach will be used that integrates state-of-the-art behavioral
assays, brain slice physiology, pharmacology, optogenetics, viral vector strategies, and molecular biology for
mechanistic loss and gain of function analyses of SK channels in the amygdala output region (central nucleus,
CeA) in the well-established spinal nerve ligation (SNL) rat model of neuropathic pain. We will use posthoc
analysis of biocytin-labelled CeA neurons and a novel transgenic Crh-Cre rat model to study SK dysfunction in
corticotropin releasing factor (CRF) containing CeA neurons that are known to project to brain centers for
behavioral regulation (Pomrenze et al., 2015). CRF plays an important role in amygdala plasticity
(Neugebauer, 2015). Aim 1 will determine the behavioral significance of loss and rescue of SK2 channel
function in neuropathic pain. Sensory thresholds, emotional responses, and anxiety- and depression-like
behaviors will be measured. Aim 2 will determine electrophysiological mechanisms of SK2 channel dysfunction
and rescue in neuropathic pain, using patch-clamp recordings of CeA neurons in brain slices from behaviorally
tested rats. Aim 3 will determine molecular mechanisms of SK2 channel dysfunction and regulation, and
validate gene transfer rescue, using CeA tissue from behaviorally tested rats. Successful completion of...

## Key facts

- **NIH application ID:** 9830677
- **Project number:** 5R01NS038261-21
- **Recipient organization:** TEXAS TECH UNIVERSITY HEALTH SCIS CENTER
- **Principal Investigator:** Volker Neugebauer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $334,688
- **Award type:** 5
- **Project period:** 1999-07-01 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9830677

## Citation

> US National Institutes of Health, RePORTER application 9830677, Amygdala pain mechanisms (5R01NS038261-21). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9830677. Licensed CC0.

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