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Voltage-Gated Calcium Channels in Nociceptors and Mechanoreceptors

Award Number: R01NS055251
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: 08/02/2006
PERIOD OF PERFORMANCE END DATE: 07/31/2026

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Voltage-Gated Calcium Channels in Nociceptors and Mechanoreceptors - Voltage-gated calcium ion channels are critically important proteins that regulate release of glutamate and substance P from nociceptors in the superficial dorsal horn of the spinal cord. As such, they serve as the gatekeepers, at the junction of the periphery and central nervous system, conveying information about touch, heat, mechanical stimulation and more to the brain. High heat or strong mechanical stimuli are noxious and perceived in the brain as painful. Neurons that detect potentially harmful signals, such as high heat, are essential for protecting the body against damage. In response to continued stimulation, such as occurs in tissue injury, these neurons can sensitize as part of a protective response, but their sensitivity usually returns to normal after healing. In certain chronic pain conditions, such as after peripheral nerve injury, the sensitivity of nociceptors fails to return to pre injury levels and normal heat and touch continue to be perceived as painful. This persistence of sensitization combined with ongoing spontaneous activity of pain circuits can result in unrelenting, chronic pain. Understanding the molecular and cellular changes that occur during the transition from normal to chronic pain states are the key to improving current – inadequate – therapies. This proposal builds on our recent discoveries and our unique expertise to determine the role of voltage-gated calcium ion channels in sensory neurons that contribute to chronic pain. We study Cacna1a and Cacna1b genes that encode the core subunits of two calcium ion channels, CaV2.1 and CaV2.2, that control transmitter release at the majority of synapses in the mammalian nervous system. We tackle two critically important questions in our overall objective to elucidate the molecular mechanisms that orchestrate Cacna1a and Cacna1b processing and their actions in different subtypes of sensory neurons that transmit information about thermal and mechanical stimuli: Aim 1. What cellular factors control the expression of the major forms of CaV2 channels in thermal and mechanical signaling? What molecular changes disrupt the normal pattern of expression of these calcium ion channels in chronic pain? Aim 2. How do different calcium ion channels function in thermal and mechanical signaling at peripheral nerve endings in skin? And do the abnormal expression patterns of different forms of ion channels contribute to the induction and maintenance of abnormal signaling? Our research addresses major gaps in our understanding, and the results will contribute to new strategies and reveal new targets for pharmacological or genetic approaches, to mitigate certain forms of chronic pain experienced by millions of people in the United States.


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 = $432,983 )
2025	2025	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	18	8/5/2025	NON-COMPETING CONTINUATION	$485,744
2025	2025	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	18	8/27/2025	NON-COMPETING CONTINUATION	-$52,761
														Subtotal = $432,983

Issue Date FY: 2024 ( Subtotal = $554,477 )
2024	2024	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	17	7/16/2024	NON-COMPETING CONTINUATION	$471,171
2024	2024	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	17	7/29/2024	SUPPLEMENT FOR EXPANSION	$83,306
														Subtotal = $554,477

Issue Date FY: 2023 ( Subtotal = $741,709 )
2023	2023	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	16	8/9/2023	SUPPLEMENT FOR EXPANSION	$83,306
2023	2023	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	16	8/21/2023	SUPPLEMENT FOR EXPANSION	$159,500
2023	2023	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	16	8/8/2023	NON-COMPETING CONTINUATION	$498,903
														Subtotal = $741,709

Issue Date FY: 2022 ( Subtotal = $582,209 )
2022	2022	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	15	7/20/2022	NON-COMPETING CONTINUATION	$498,903
2022	2022	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	003	15	7/26/2022	SUPPLEMENT FOR EXPANSION	$83,306
2022	2021	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	14	11/27/2021	COMPETING CONTINUATION	$130
2022	2018	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	13	11/27/2021	NON-COMPETING CONTINUATION	-$130
														Subtotal = $582,209

Issue Date FY: 2021 ( Subtotal = $526,502 )
2021	2021	BROWN UNIVERSITY IN PROVIDENCE IN THE STATE OF RHODE ISLAND AND PROVIDENCE PLANTATIONS	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	14	9/10/2021	COMPETING CONTINUATION	$526,502
														Subtotal = $526,502

Issue Date FY: 2020 ( Subtotal = $0 )
2020	2018	BROWN UNIVERSITY IN PROVIDENCE IN THE STATE OF RHODE ISLAND AND PROVIDENCE PLANTATIONS	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	13	6/25/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2018 ( Subtotal = $496,324 )
2018	2018	BROWN UNIVERSITY IN PROVIDENCE IN THE STATE OF RHODE ISLAND AND PROVIDENCE PLANTATIONS	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	13	7/4/2018	NON-COMPETING CONTINUATION	$496,324
														Subtotal = $496,324

Issue Date FY: 2017 ( Subtotal = $496,324 )
2017	2017	BROWN UNIVERSITY IN PROVIDENCE IN THE STATE OF RHODE ISLAND AND PROVIDENCE PLANTATIONS	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	12	7/12/2017	NON-COMPETING CONTINUATION	$496,324
														Subtotal = $496,324

Issue Date FY: 2016 ( Subtotal = $496,324 )
2016	2016	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	11	7/7/2016	NON-COMPETING CONTINUATION	$496,324
														Subtotal = $496,324

Issue Date FY: 2015 ( Subtotal = $503,338 )
2015	2015	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	10	7/16/2015	NON-COMPETING CONTINUATION	$503,338
														Subtotal = $503,338

Issue Date FY: 2014 ( Subtotal = $634,195 )
2014	2014	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	8	5/27/2014	SUPPLEMENT FOR EXPANSION	$81,250
2014	2014	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	9	9/19/2014	COMPETING CONTINUATION	$552,945
2014	2013	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	8	9/17/2014	NON-COMPETING CONTINUATION	$0
														Subtotal = $634,195

Issue Date FY: 2013 ( Subtotal = $513,950 )
2013	2013	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	8	1/10/2013	NON-COMPETING CONTINUATION	$479,333
2013	2013	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	8	5/24/2013	NON-COMPETING CONTINUATION	$34,617
														Subtotal = $513,950

Issue Date FY: 2012 ( Subtotal = $532,729 )
2012	2012	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	7	2/6/2012	NON-COMPETING CONTINUATION	$532,729
														Subtotal = $532,729

Issue Date FY: 2011 ( Subtotal = $531,566 )
2011	2011	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	6	6/7/2011	NON-COMPETING CONTINUATION	$34,109
2011	2011	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	6	2/7/2011	NON-COMPETING CONTINUATION	$497,457
														Subtotal = $531,566

Issue Date FY: 2010 ( Subtotal = $587,046 )
2010	2010	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	002	5	2/4/2010	COMPETING CONTINUATION	$549,609
2010	2009	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	2/3/2010	NON-COMPETING CONTINUATION	$37,437
2010	2009	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	2/3/2010	NON-COMPETING CONTINUATION	$0
														Subtotal = $587,046

Issue Date FY: 2009 ( Subtotal = $494,759 )
2009	2009	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Trans-NIH Recovery Act Research Support	002	4	9/22/2009	SUPPLEMENT FOR EXPANSION	$120,393
2009	2009	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	1/14/2009	NON-COMPETING CONTINUATION	$336,929
2009	2009	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	4	4/6/2009	NON-COMPETING CONTINUATION	$37,437
														Subtotal = $494,759

Issue Date FY: 2008 ( Subtotal = $374,924 )
2008	2008	BROWN UNIVERSITY	POST OFFICE BOX 1929	PROVIDENCE	RI	02912	PROVIDENCE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	1/18/2008	NON-COMPETING CONTINUATION	$374,924
														Subtotal = $374,924

Issue Date FY: 2007 ( Subtotal = $371,371 ) (Continued on the next page)
Grand Total All Awards = $9,104,113

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Voltage-Gated Calcium Channels in Nociceptors and Mechanoreceptors

Award Number: R01NS055251

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: 08/02/2006

PERIOD OF PERFORMANCE END DATE: 07/31/2026

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