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Peripheral Mechanisms of Kappa Opioid Receptor-Mediated Cold Hypersensitivity

Award Number: R01NS123070
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: 04/01/2022
PERIOD OF PERFORMANCE END DATE: 03/31/2027

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Peripheral Mechanisms of Kappa Opioid Receptor-Mediated Cold Hypersensitivity - Project Summary The overall goal of this research is to better understand the how the kappa opioid receptor (KOR) system modulates cold hypersensitivity with the ultimate goal of uncovering a novel therapeutic target. Cold pain affects a number of diverse groups of patients and goes largely untreated. Neuropathic pain with cold allodynia is estimated to affect 15% to 50% of neuropathic pain patients. For many patients, cold pain is often a side effect that becomes a chronic debilitating condition. Patients undergoing chemotherapy using platinum-based drugs report increased sensitivity and pain to cold stimuli. Furthermore, heightened sensitivity to cold is problematic in those diagnosed with multiple sclerosis. For others, cold pain is part of larger more complex pain condition. The most commonly reported medications used to treat neuropathic pain are non-steroidal anti-inflammatory drugs (NSAIDs), opioids and anti-epileptics, which do not relieve or treat heightened cold sensitivity, primarily because we do not have clear understanding of the mechanisms involved in the modulation of cold pain. This research focuses on better understanding the mechanism by which peripheral KORs modulate cold hypersensitivity and cold pain. The first aim of this proposal will use combined transgenic and pharmacological approaches to assess the necessity of peripheral KOR expression in the modulation of cold hypersensitivity and cold pain. The second aim will determine the mechanism by which KORs in dorsal root ganglion can modulate TRPA1 signaling, as well as determine the necessity of the involvement of TRPA1 channels in KOR mediated cold hypersensitivity. The third aim will test whether KORs in dorsal root ganglion also modulate TRPM8 signaling. In the final aim, will use human dorsal root ganglion tissue from organ donors to determine if the KOR-modulation of TRP function exists in humans. Together, these approaches will allow us to dissect the role of peripheral kappa opioids in cold hypersensitivity and cold pain. Understanding the mechanisms by which the KOR system modulates cold hypersensitivity and how this system may also be involved in modulation of cold pain will have major implications not only in our understanding of basic mechanisms of cold hypersensitivity, but may also open up alternative therapeutic targets to allow us to treat cold hypersensitivity and 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 = $0 )
2025	2023	UNIVERSITY OF HEALTH SCIENCES AND PHARMACY IN ST. LOUIS	1 PHARMACY PL	SAINT LOUIS	MO	63110	SAINT LOUIS CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	2/25/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $358,980 )
2024	2024	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63110	SAINT LOUIS CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	5/30/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$358,980
2024	2023	UNIVERSITY OF HEALTH SCIENCES AND PHARMACY IN ST. LOUIS	1 PHARMACY PL	SAINT LOUIS	MO	63110	SAINT LOUIS CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	5/30/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $358,980

Issue Date FY: 2023 ( Subtotal = $427,807 )
2023	2023	UNIVERSITY OF HEALTH SCIENCES AND PHARMACY IN ST. LOUIS	1 PHARMACY PL	SAINT LOUIS	MO	63110	SAINT LOUIS CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	3/17/2023	NON-COMPETING CONTINUATION	$427,807
														Subtotal = $427,807

Issue Date FY: 2022 ( Subtotal = $441,584 )
2022	2022	UNIVERSITY OF HEALTH SCIENCES AND PHARMACY IN ST. LOUIS	1 PHARMACY PL	SAINT LOUIS	MO	63110	SAINT LOUIS CITY	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	3/31/2022	NEW	$441,584
														Subtotal = $441,584

Grand Total All Awards = $1,228,371

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Peripheral Mechanisms of Kappa Opioid Receptor-Mediated Cold Hypersensitivity

Award Number: R01NS123070

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: 04/01/2022

PERIOD OF PERFORMANCE END DATE: 03/31/2027

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