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Investigation of the endogenous opioid neural circuitry in pain

Award Number: R03DA058194
ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/15/2023
PERIOD OF PERFORMANCE END DATE: 08/31/2025

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Investigation of the endogenous opioid neural circuitry in pain - PROJECT SUMMARY The opioid epidemic has encouraged the biomedical research community to explore new pain targets and further study opioid’s most famous target, the mu opioid receptor. One underexplored arena is the study of the endogenous opioid peptide system, which we know very little especially in comparison to our knowledge of the receptors they activate. This is despite the commonsense understanding that the endogenous peptides must change as a result of the allostatic load imposed by chronic pain, opioids, and chronic opioid exposure. There are well established sex differences in the actions of opioids at the mu opioid receptor, but it is unknown whether there are also differences in the endogenous opioid peptides. The experiments outlined here lay the necessary and long overdue groundwork to understand the neural mechanisms of one class of the endogenous opioids, called enkephalins, and how they contribute to pain. In the first aim, we will quantify enkephalin mRNA expression in regions of the brain known to play a role in top-down pain modulation. Next, we will use a viral retrograde tracer to map the enkephalin containing neurons that synapse in the PAG, something that has never been done before. In Aim 2 we will probe the behavioral effects of activating enkephalin containing neurons that synapse in the PAG using excitatory and inhibitory chemogenetic approaches followed by assessment on pain assays. We expect that increasing activation of all enkephalin neurons that synapse in the PAG will result in increased antinociception. Further, we expect that inhibition will lower the endogenous opioid release and therefore produce pain. We will further isolate certain neural projections from one brain region at a time to elucidate which brain regions are driving the enkephalin mediated antinociceptive responses. This research will allow us to better understand how the endogenous opioid system facilitates pain control and whether there are underlying differences that lead to differences in pain modulation in males and females.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $0 )
2026	2024	UTAH STATE UNIVERSITY	1000 OLD MAIN HL	LOGAN	UT	84322	CACHE	USA	Drug Use and Addiction Research Programs	000	2	2/25/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $73,000 )
2024	2024	UTAH STATE UNIVERSITY	1000 OLD MAIN HL	LOGAN	UT	84322	CACHE	USA	Drug Use and Addiction Research Programs	001	2	7/30/2024	NON-COMPETING CONTINUATION	$73,000
2024	2023	UTAH STATE UNIVERSITY	1000 OLD MAIN HL	LOGAN	UT	84322	CACHE	USA	Drug Use and Addiction Research Programs	000	1	11/8/2023	NEW	$0
														Subtotal = $73,000

Issue Date FY: 2023 ( Subtotal = $73,000 )
2023	2023	UTAH STATE UNIVERSITY	1000 OLD MAIN HILL	LOGAN	UT	84322	CACHE	USA	Drug Use and Addiction Research Programs	000	1	9/13/2023	NEW	$73,000
														Subtotal = $73,000

Grand Total All Awards = $146,000

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Investigation of the endogenous opioid neural circuitry in pain

Award Number: R03DA058194

ORGANIZATION: NATIONAL INSTITUTE ON DRUG ABUSE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/15/2023

PERIOD OF PERFORMANCE END DATE: 08/31/2025

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