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Oxytocin: a pain disease-modifying agent in the nervous system after injury

Award Number: P01NS119159
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: 04/15/2022
PERIOD OF PERFORMANCE END DATE: 03/31/2027

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Oxytocin: a pain disease-modifying agent in the nervous system after injury - This P01 will address fundamental gaps in knowledge that currently impede translation of findings in the preclinical literature to improved clinical practice regarding the utility of oxytocin as a pain therapeutic and potential disease-modifying agent to prevent the transition from acute to chronic pain. Oxytocin itself is the only clinically available tool for translational studies in many areas – neuroprotection, anxiety, sleep, social behaviors, addiction, and pain. Most rodent and human studies of oxytocin lack strong scientific rigor, with only half of the clinical studies examining pain demonstrating efficacy, and we have minimal ability to understand oxytocin effects within and across species. Since chronic pain is usually reduced acutely by peripheral nerve block, peripheral input is necessary, but most research assumes that input is normal and pain reflects ongoing central sensitization. We and others challenge these ideas, showing that LTMRs are desensitized after injury whereas fast high threshold mechanoreceptors (A-HTMRs) are sensitized and behavioral recovery coincides with return to normal function of both afferent subtypes. Importantly, oxytocin acutely moves LTMR and A-HTMR dysfunction after injury towards normal. Pain resolves quicker in women after cesarean delivery than other pelvic surgeries, and hypersensitivity resolves quicker in rodents when neuropathic injury is performed after delivery, an effect blocked by inhibition of oxytocin action. These data suggest that oxytocin may alter the process of chronic pain development after injury or surgery, and has the potential to be not just an acute analgesic, but a disease-modifying therapeutic. Oxytocin has prosocial, anxiolytic, and trust enhancing effects according to small studies in rodents and humans, but the circuitry and role of these central actions on speeding recovery from pain and disability after injury are unexplored. This P01 will address these gaps and advance the field of pain research through the coordinated interactions between the preclinical and clinical projects across 3 specific areas. The first is extrapolation of the pharmacokinetics of oxytocin across species, such that drug exposure in relevant compartments with time are being studied in a coordinated manner that permits interpretation of physiological or behavioral effects between rats and humans Second is the study of primary sensory afferent physiology across species that determines how oxytocin alters specific nerve fiber types and the key electrical properties related to pain transmission, including multiple modes of nociceptive stimulation and their interaction. Third, we study pain behaviors beyond reflexive responses or verbal report in animals and humans, respectively, which may offer greater translational value. Collectively, the coordinated and synergistic nature of these studies will hopefully provide clarity on the potential of oxytocin to mitigate chronic pain development after injury, and the context within such effects occur.


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 = $1,639,004 )
2026	2026	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	4/17/2026	NON-COMPETING CONTINUATION	$1,639,004
														Subtotal = $1,639,004

Issue Date FY: 2025 ( Subtotal = $1,804,300 )
2025	2025	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	4/7/2025	NON-COMPETING CONTINUATION	$1,804,300
														Subtotal = $1,804,300

Issue Date FY: 2024 ( Subtotal = $1,620,081 )
2024	2024	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	3	4/11/2024	NON-COMPETING CONTINUATION	$1,620,081
2024	2023	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	11/24/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,620,081

Issue Date FY: 2023 ( Subtotal = $1,742,343 )
2023	2023	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	5/11/2023	NON-COMPETING CONTINUATION	$1,742,343
														Subtotal = $1,742,343

Issue Date FY: 2022 ( Subtotal = $1,997,998 )
2022	2022	WAKE FOREST UNIVERSITY HEALTH SCIENCES	MEDICAL CENTER BLVD	WINSTON SALEM	NC	27157	FORSYTH	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	4/14/2022	NEW	$1,997,998
														Subtotal = $1,997,998

Grand Total All Awards = $8,803,726

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Oxytocin: a pain disease-modifying agent in the nervous system after injury

Award Number: P01NS119159

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: 04/15/2022

PERIOD OF PERFORMANCE END DATE: 03/31/2027

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