# Involvement of dopamine signaling in chronic pain-induced negative affective state and nicotine use comorbidity

> **NIH NIH K01** · YALE UNIVERSITY · 2023 · $180,033

## Abstract

Project Summary/Abstract
Nicotine addiction among individuals with chronic pain is a serious public health concern with significant health-
care expenses and lost productivity. Chronic pain-associated negative affective state, such as anxiety, is a risk
factor for tobacco use. Greater chronic pain intensity increases sensitivity to anxiety, which is, in turn, associated
with increased smoking and vaping. Therefore, I hypothesize there is a neurobiological mechanism in which
chronic pain decreases mesolimbic dopaminergic signaling to causally induce a negative affective state, thereby
increasing the risk of nicotine use. To investigate this causal mechanism in the comorbidity of chronic pain and
nicotine use, I propose modeling this comorbidity in rats and the following aims: Aim 1: Evaluate ventral
tegmental area – nucleus accumbens (VTA-NAc) dopamine (DA) signaling in a model of chronic pain to
determine whether decreases in DA signaling underlie the chronic pain-induced negative affective state. Aim 2:
Determine whether nicotine has increased reinforcing efficacy in chronic pain states compared to pain-naïve
states. This proposal combines behavioral, pharmacological, neurochemical, and optogenetic approaches to
reveal whether chronic pain-associated decreases in VTA-NAc DA signaling underlie chronic pain-induced
negative affective states, and whether nicotine is more rewarding in chronic pain states compared to pain-naïve
states due to decreased baseline DA signaling, thereby exacerbating nicotine’s effects on DA signaling.
My overall career goal is to become an independent academic scientist, identifying neurobiological mechanisms
underlying these phenomena to develop new interventions for patients with co-morbid pain and nicotine
addiction. The proposed K01 trainings will increase my knowledge of neurobiology and circuitry of the mesolimbic
reward pathway, allowing me to investigate its mediation in chronic pain-induced negative affect and nicotine
addiction. My primary mentor Dr. Addy, an expert in neurobiology and neurochemistry of substance abuse and
Director of Scientist Diversity and Inclusion at Yale, will provide training on mechanisms of drug reinforcement
and in vivo voltammetry along with insight into building an inclusive and diverse work environment. My co-mentor
Dr. DiLeone, an expert in neuronal circuits controlling reward-related behaviors, will provide training on
neuromodulation and in vivo optogenetics. My co-mentor Dr. Porreca, an expert in pain-induced affective and
motivational behaviors and reward circuits, will provide training and oversight on modeling and understanding
brain reward circuitry in chronic pain and negative affect. My co-mentor Dr. Picciotto, the director of the Junior
Faculty Mentoring Program for the Department of Psychiatry at Yale, will mentor my career enhancement
trainings together with Dr. Addy. My consultant Dr. Ditre, an expert in human comorbidity of chronic pain and
nicotine addiction, will pro...

## Key facts

- **NIH application ID:** 10662951
- **Project number:** 1K01DA056854-01A1
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Deniz Bagdas
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $180,033
- **Award type:** 1
- **Project period:** 2023-04-01 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10662951

## Citation

> US National Institutes of Health, RePORTER application 10662951, Involvement of dopamine signaling in chronic pain-induced negative affective state and nicotine use comorbidity (1K01DA056854-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10662951. Licensed CC0.

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