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Circuitry and Molecular Mechanisms for Descending Pain Facilitation

Award Number: R01NS129834
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: 12/01/2022
PERIOD OF PERFORMANCE END DATE: 11/30/2027

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Circuitry and Molecular Mechanisms for Descending Pain Facilitation - Abstract Chronic pain is a pervasive global health issue affecting about 20% of individuals worldwide, but available treatments for chronic pain are still inadequate. Opiates have been used for centuries as potent analgesics, but issues with tolerance, abuse, and overdose have contributed to current opioid crisis in the US. On the other hand, it is well documented that the level of perceived pain can be strongly influenced by cognitive and mood states, revealing the existence of powerful endogenous top-down modulation of pain. However, the therapeutic potential of targeting descending pain modulation pathway in treating chronic pain has not been extensively explored, in a large part because of our poor understanding of the circuitry and molecular mechanisms underlying how these descending pathways engage in chronic pain. In our preliminary studies, we developed novel genetic and viral tools, and gained robust access to the -opioid receptor expressing spinal cord projecting neurons in the rostroventral medulla (OPRM+ RVMSC neurons). We demonstrated that the OPRM+ RVMSC neurons has limited contribution to normal nociception but is required for both initiation and maintenance of nerve injury induced chronic mechanical pain. We therefore established these neurons as a potent cellular target for treating chronic pain. In this proposal, we will further examine the circuitry (Aim1) and molecular (Aim2) mechanisms that engage the OPRM+ RVMSC neurons in chronic pain. These proposed studies will not only advance our understanding of how the OPRM+ RVMSC neurons is recruited in chronic pain, but also inspire the development of novel non-opioid treatment for chronic pain.


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: 2025 ( Subtotal = $403,368 )
2025	2025	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	11/20/2024	NON-COMPETING CONTINUATION	$403,368
														Subtotal = $403,368

Issue Date FY: 2024 ( Subtotal = $434,741 )
2024	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	12/1/2023	NON-COMPETING CONTINUATION	$403,368
2024	2024	THE LELAND STANFORD JUNIOR UNIVERSITY	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	2	4/24/2024	NON-COMPETING CONTINUATION	$31,373
														Subtotal = $434,741

Issue Date FY: 2023 ( Subtotal = $448,186 )
2023	2023	LELAND STANFORD JUNIOR UNIVERSITY, THE	450 JANE STANFORD WAY	STANFORD	CA	94305	SANTA CLARA	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	11/24/2022	NEW	$448,186
														Subtotal = $448,186

Grand Total All Awards = $1,286,295

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Circuitry and Molecular Mechanisms for Descending Pain Facilitation

Award Number: R01NS129834

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: 12/01/2022

PERIOD OF PERFORMANCE END DATE: 11/30/2027

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