# The contribution of chronic pain-associated thalamocortical activity to pain aversiveness

> **NIH NIH F32** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $69,788

## Abstract

PROJECT SUMMARY
Injury to the peripheral nervous system can provoke recurring pain and negative affect comorbidity, an explicit
burden of chronic pain patients. In humans and preclinical models, neuropathic pain involves the sensitization
of peripheral and central circuits that underlie ongoing pain and produce allodynia, in which innocuous stimuli
are now painful. Although we understand much of the anatomy and physiology of the processing of injury
information from the periphery to the brain, our knowledge of how forebrain circuits generate the pain percept
and its affective component is limited. Our recent studies indicate that afferent activity within the mediodorsal
thalamus (MD) connection to the anterior cingulate cortex (ACC) selectively drives aversive conditioning in
chronic pain states. The conditioning results from a plasticity mechanism in the ACC, one that increases the
correlation between MD activity and aversive behavior. These findings are the basis of our hypothesis that MD-
ACC neuronal activity, in chronic pain states, is a determinant of aversiveness, and that it is separate from
nociception. To challenge our hypothesis, we propose an innovative combination of in vivo microendoscopy
and circuit-specific labeling to measure MD-ACC activity at baseline, in response to investigator-evoked stimuli
and in an operant environment, using two nerve-injury induced preclinical pain models. Our specific aims focus
on 1. Determining if MD-ACC activity specifically encodes pain-related states, rather than acute nociception; 2.
Testing whether inhibition of MD-ACC activity attenuates pain aversiveness selectively in chronic pain
conditions; and 3. Assessing if analgesics interact differentially with MD-ACC activity in connection with their
potency against pain aversiveness. Information gained from these studies will highlight the therapeutic potential
of targeting the MD (e.g., with novel pharmacotherapeutics) in ongoing pain states and elaborate our knowledge
of when and where brain activity becomes abnormal after an injury to the peripheral nervous system.

## Key facts

- **NIH application ID:** 10053677
- **Project number:** 5F32DE029384-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Andrew Joseph Crowther
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $69,788
- **Award type:** 5
- **Project period:** 2020-03-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10053677

## Citation

> US National Institutes of Health, RePORTER application 10053677, The contribution of chronic pain-associated thalamocortical activity to pain aversiveness (5F32DE029384-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10053677. Licensed CC0.

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