# The role of delta opioid receptors in trigeminovascular pain

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2020 · $354,350

## Abstract

Project Summary/Abstract
Over 2 million people in the United States suffer from prescription drug abuse of opioid analgesics. One of the
leading causes for the prescription of opioids is for the treatment of trigeminovascular pain (migraine); and the
majority of these treatments target the µ opioid receptor. These µ agonists have poor efficacy for
trigeminovascular pain, contribute to the progression of pain from an episodic to chronic state, and serve as an
entry point to prescription drug abuse. Drugs that selectively activate the δ opioid receptor have distinct
properties which make them promising alternatives to currently used µ-based therapies. We have recently
developed a novel model of trigeminovascular pain, using the known human migraine trigger nitroglycerin (NTG).
Chronic intermittent treatment with NTG results in acute and chronic hyperalgesia, which is inhibited by δ
agonists. In addition, we have also shown that the δ agonist SNC80 can inhibit cortical spreading depression, a
“gold standard” model of aura associated with trigeminovascular pain. The continued development of δ agonists
for migraine depends upon a better understanding of where and how δ agonists inhibit trigeminovascular pain
and related symptoms. δ opioid receptors are expressed in several central and peripheral regions that are
important in pain processing, and emotional modulation. Which δORs are anatomically important for regulating
trigeminovascular pathophysiology is currently unknown. A goal of this proposal will be to determine the role of
central vs. peripheral δ opioid receptors in the development and treatment of trigeminovascular pain. For this
purpose, we will use novel conditional knockout (cKO) mice with δ opioid receptors deleted in specific central
and peripheral regions. We will examine the effects of these specific knockouts in the NTG model of
trigeminovascular pain and negative affect, and on cortical spreading depression. We will also explore the
mechanism by which δ agonists inhibit trigeminovascular pain. The neuropeptide, calcitonin gene related peptide
(CGRP) plays a pivotal role in the induction and maintenance of trigeminovascular pain, primarily through the
peripheral afferents projecting from the trigeminal ganglia. A further aim of this proposal will be to determine the
expression of δORs on CGRP-expressing ganglia, as well as changes in CGRP release, when animals are
naïve, in trigeminovascular pain, and chronically treated with δ agonists. Together, these studies will provide a
deeper insight into how δORs affect trigeminovascular pain, thus enhancing the development of novel
therapeutic compounds for this disorder.

## Key facts

- **NIH application ID:** 9938521
- **Project number:** 5R01DA040688-05
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Amynah Amir Ali Pradhan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $354,350
- **Award type:** 5
- **Project period:** 2016-08-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9938521

## Citation

> US National Institutes of Health, RePORTER application 9938521, The role of delta opioid receptors in trigeminovascular pain (5R01DA040688-05). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/9938521. Licensed CC0.

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