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From the spinal cord to the brain: Neurology of the pain and itch neurons

Award Number: R35NS097306
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: 12/01/2016
PERIOD OF PERFORMANCE END DATE: 11/30/2024

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From the spinal cord to the brain: Neurology of the pain and itch neurons - Despite tremendous progress in our understanding of the primary sensory neurons and spinal cord interneuronal circuits that respond to and transmit pain and itch-provoking stimuli, how these stimuli are interpreted by the brain to produce the perceptions of pain and itch are still unclear. To a great extent, this gap in our knowledge reflects the much more limited information that we have about the projection neurons that carry the information from the spinal cord to the brain. That gap is critical as it is the signals carried by the projection neurons that are “read” by the brain and that ultimately lead to a perception of pain or itch, and to their various submodalities (heat, cold, mechanical, etc.). Our research program is multidisciplinary, using novel viral, genetic and functional (electrophysiological, behavioral and imaging) approaches to characterize the properties of the projection neurons, the circuits that engage them, their supraspinal targets and the functional consequence of their activity. An important focus of the research program is on the question of convergence or segregation of the circuits that respond to painful or itch-provoking stimuli and the extent to which these circuits are altered in the setting of injury. Our program includes several highly innovative experiments that for the first time will not only determine the molecular heterogeneity of the projection neurons, but will also examine the responses of populations of neurons in the brain to activity in the projection neurons. Defining molecular subtypes of projection neurons and the development of Cre-expressing mice based on these molecular features will permit a host of experiments, including viral-based retrograde (rabies) and anterograde (HSV) tracing of circuits that influence subsets of projection neurons, as well as the behavioral consequence of selective ablation, or DREADD-mediated activation/inhibition of these neurons. Finally, using incredibly powerful Ca2+ imaging techniques that signal the activity of populations of neurons in awake, freely moving mice, we will obtain new information on the behavioral correlates of algogen and pruritogen-evoked supraspinal activity. Using novel behavioral paradigms our program will also provide important insights into the processes through which noxious, and even innocuous stimuli (in the setting of injury), are interpreted as painful. These new approaches will provide information about the quality of the pain that the animal experiences and also offer a powerful validation of the mouse models of chronic pain and itch and their translatability to the human condition.


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: 2024 ( Subtotal = $922,471 )
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	8	4/23/2024	NON-COMPETING CONTINUATION	$66,571
2024	2024	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	8	12/4/2023	NON-COMPETING CONTINUATION	$855,900
														Subtotal = $922,471

Issue Date FY: 2023 ( Subtotal = $951,000 )
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	7	4/24/2023	NON-COMPETING CONTINUATION	$0
2023	2023	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	7	1/11/2023	NON-COMPETING CONTINUATION	$951,000
														Subtotal = $951,000

Issue Date FY: 2022 ( Subtotal = $951,000 )
2022	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	6	1/13/2022	SUPPLEMENT FOR EXPANSION	$158,500
2022	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	6	1/7/2022	NON-COMPETING CONTINUATION	$713,252
2022	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	6	3/24/2022	NON-COMPETING CONTINUATION	$79,248
														Subtotal = $951,000

Issue Date FY: 2021 ( Subtotal = $769,857 )
2021	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	12/21/2020	NON-COMPETING CONTINUATION	$775,901
2021	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	5	6/23/2021	NON-COMPETING CONTINUATION	-$144,912
2021	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	5	2/25/2021	NON-COMPETING CONTINUATION	$188,141
2021	2020	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	4	6/23/2021	NON-COMPETING CONTINUATION	-$49,273
														Subtotal = $769,857

Issue Date FY: 2020 ( Subtotal = $1,068,794 )
2020	2020	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	4	1/21/2020	SUPPLEMENT FOR EXPANSION	$100,735
2020	2020	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	4	8/6/2020	NON-COMPETING CONTINUATION	$98,259
2020	2020	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	005	4	8/6/2020	SUPPLEMENT FOR EXPANSION	$0
2020	2020	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	12/6/2019	NON-COMPETING CONTINUATION	$35,174
2020	2020	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	11/19/2019	NON-COMPETING CONTINUATION	$834,626
2020	2019	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	004	3	8/6/2020	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $1,068,794

Issue Date FY: 2019 ( Subtotal = $939,592 )
2019	2019	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	1/17/2019	NON-COMPETING CONTINUATION	$894,580
2019	2019	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	8/13/2019	SUPPLEMENT FOR EXPANSION	$45,012
														Subtotal = $939,592

Issue Date FY: 2018 ( Subtotal = $894,580 )
2018	2018	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 420	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	2	3/29/2018	NON-COMPETING CONTINUATION	$0
2018	2018	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 420	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	12/18/2017	NON-COMPETING CONTINUATION	$771,213
2018	2018	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 420	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	2	6/4/2018	NON-COMPETING CONTINUATION	$123,367
2018	2017	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 420	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	1	3/27/2018	SUPPLEMENT FOR EXPANSION	$0
2018	2017	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	005	1	7/9/2018	SUPPLEMENT FOR EXPANSION	$34,026
2018	2017	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	004	1	7/9/2018	SUPPLEMENT FOR EXPANSION	-$34,026
														Subtotal = $894,580

Issue Date FY: 2017 ( Subtotal = $652,715 )
2017	2017	UNIVERSITY OF CALIFORNIA, SAN FRANCISCO	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	11/25/2016	NEW	$618,689
2017	2017	UNIVERSITY OF CALIFORNIA, SAN FRANCISCO	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	1	7/11/2017	SUPPLEMENT FOR EXPANSION	$34,026
														Subtotal = $652,715

Grand Total All Awards = $7,150,009

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From the spinal cord to the brain: Neurology of the pain and itch neurons

Award Number: R35NS097306

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: 12/01/2016

PERIOD OF PERFORMANCE END DATE: 11/30/2024

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