Wednesday, December 31, 2025 12/31/2025

Investigation of neural ensembles driving pain chronification

Award Number: R01NS130044
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/15/2022
PERIOD OF PERFORMANCE END DATE: 11/30/2027

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Investigation of neural ensembles driving pain chronification - PROJECT SUMMARY The unpleasantness, or negative affective component, of pain perception is an emotional phenomenon distinct from the perceptive sensory qualities. This affective dimension of pain underlies the suffering and motivational deficits of chronic pain patients. However, similar cellular-resolution mechanisms within brain networks is lacking relative to the intricate nociceptive detail in the peripheral and spinal circuits. Thus, a key step toward accelerating the development of effective pain treatments must be the discovery of the specific neural circuits in the brain that are responsible for the aversive and unpleasant quality of pain perception. We recently reported the discovery and characterization of a basolateral amygdalar (BLA) neural ensemble, at single neuron resolution, that transforms nociceptive information in affective-motivational behavior in both acute and chronic pain conditions. While these studies provide a critical point of entry into the complex affective circuits of pain, it is not clear how the BLA nociceptive ensemble connects with other parts of the larger affective brain circuitry. Our goal here is to provide a systems-level understanding of the nociceptive cortical brain networks involved in the affective perception of pain by integrating multimodal data from pain-experience-dependent transcriptomics, activity based whole-brain circuit tracing, and precision chemogenetic control—anchored in motivational behavior-based classifications—throughout the transition from acute to chronic pain. Thus, to discover this nociceptive brain network, in AIM 1 we will use a rabies viral-genetic strategy combined with immediate early gene mapping in cleared, intact brain tissue to locate key neuronal populations whose activity is altered by chronic neuropathic pain. In AIM 2, we will employ single-nuclei RNA sequencing to link transcriptomic identity and change in cellular states during pain chronification in defined nociceptive input cells to the BLA noci- ensemble. In AIM 3, we will chemogenetically manipulate nociceptive cell-types projecting to the BLA to mitigate pain affective-motivational behaviors with locally infused microsphere drug-delivery. The cellular and functional identification of these fundamental nociceptive circuits should open new avenues for developing precision therapeutics to combat different dimensions of pain experiences, including the unpleasant affective component. Such circuit-targeted therapies could selectively diminish the suffering of pain patients, regardless of etiology and without influencing reward, while preserving necessary sensory discriminative processes for protective pain sensation.


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 = $301,475 )
2026	2026	UNIVERSITY OF CALIFORNIA IRVINE	160 ALDRICH HALL	IRVINE	CA	92697	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	12/5/2025	NON-COMPETING CONTINUATION	$301,475
														Subtotal = $301,475

Issue Date FY: 2025 ( Subtotal = $338,163 )
2025	2025	UNIVERSITY OF CALIFORNIA IRVINE	160 ALDRICH HALL	IRVINE	CA	92697	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	8/7/2025	NON-COMPETING CONTINUATION	$33,817
2025	2025	UNIVERSITY OF CALIFORNIA IRVINE	160 ALDRICH HALL	IRVINE	CA	92697	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	11/8/2024	NON-COMPETING CONTINUATION	$304,346
														Subtotal = $338,163

Issue Date FY: 2024 ( Subtotal = $331,025 )
2024	2024	UNIVERSITY OF CALIFORNIA IRVINE	160 ALDRICH HALL	IRVINE	CA	92697	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	4/24/2024	NON-COMPETING CONTINUATION	$86,894
2024	2024	UNIVERSITY OF CALIFORNIA IRVINE	160 ALDRICH HALL	IRVINE	CA	92697	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	11/29/2023	NON-COMPETING CONTINUATION	$244,131
														Subtotal = $331,025

Issue Date FY: 2023 ( Subtotal = $348,174 )
2023	2023	UNIVERSITY OF CALIFORNIA, IRVINE	160 ALDRICH HALL	IRVINE	CA	92697	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	1	6/27/2023	SUPPLEMENT FOR EXPANSION	$59,660
2023	2023	UNIVERSITY OF CALIFORNIA, IRVINE	160 ALDRICH HALL	IRVINE	CA	92697	ORANGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	12/9/2022	NEW	$288,514
														Subtotal = $348,174

Grand Total All Awards = $1,318,837

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Investigation of neural ensembles driving pain chronification

Award Number: R01NS130044

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 12/15/2022

PERIOD OF PERFORMANCE END DATE: 11/30/2027

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