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Functional peripheral and central vagal neural circuits of interoception inhibiting pain

Award Number: R01DE031477
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/01/2022
PERIOD OF PERFORMANCE END DATE: 12/31/2026

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Functional peripheral and central vagal neural circuits of interoception inhibiting pain - Functional peripheral and central vagal neural circuits of interoception inhibiting pain Interoception is the sense of the physiological condition of the body, and is critical for maintaining homeostasis and regulating cognitive and emotional processes. The neural processing of interoception can be regulated by electrical stimulation of the vagus nerve, which led to an FDA-approved therapy for seizure and depression. Interestingly, vagal stimulation also modulates intractable chronic pain in patients. However, the road to improving chronic pain management through the regulation of interoceptive inputs is blocked by our ignorance of the neurobiological mechanisms whereby vagal activity modulates chronic pain, posing a significant hurdle. To overcome this hurdle, we will focus on the neural mechanisms of vagal modulation in a mouse model of inflammation in temporomandibular joint (TMJ), a surrogate model of temporomandibular disorders (TMD). TMD is a prevalent form of chronic pain that often occurs as a comorbidity with other chronic pain conditions, such as migraine and fibromyalgia. Since chronic pain involves a wide range of neural processes ranging from peripheral nociception to affective and cognitive processing in the brain, it is possible that interoceptive inputs regulate pain pathways through multiple peripheral and central mechanisms. Vagal stimulation was suggested to inhibit transmission of pain signals at spinal cord through the regulation of descending pain modulatory pathways. Considering the high comorbidity of chronic pain and affective disorders, such as anxiety or depression, vagal inputs likely modulate pain through regulation of brain regions involved in emotional regulation. Furthermore, pain is driven by nociceptive processing by pain-sensing nerves at peripheral tissues, but vagal regulation of nociception in the periphery has not been reported. Here, our objective is to determine functional neural mechanisms by which interoception inhibits pain. Our central hypothesis is that vagal interoceptive circuits intersect with peripheral and central nociceptive pathways to inhibit pain from TMJ. We will test this hypothesis in the following specific aims.


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 = $724,588 )
2025	2025	THE UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Oral Diseases and Disorders Research	001	4	5/5/2025	NON-COMPETING CONTINUATION	$72,458
2025	2025	THE UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Oral Diseases and Disorders Research	000	4	1/6/2025	NON-COMPETING CONTINUATION	$652,130
														Subtotal = $724,588

Issue Date FY: 2024 ( Subtotal = $710,096 )
2024	2024	THE UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Oral Diseases and Disorders Research	001	3	6/17/2024	NON-COMPETING CONTINUATION	$57,966
2024	2024	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Oral Diseases and Disorders Research	000	3	11/30/2023	NON-COMPETING CONTINUATION	$652,130
														Subtotal = $710,096

Issue Date FY: 2023 ( Subtotal = $724,588 )
2023	2023	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Oral Diseases and Disorders Research	001	2	2/14/2023	NON-COMPETING CONTINUATION	$72,458
2023	2023	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Oral Diseases and Disorders Research	000	2	12/28/2022	NON-COMPETING CONTINUATION	$652,130
														Subtotal = $724,588

Issue Date FY: 2022 ( Subtotal = $1,003,618 )
2022	2022	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Oral Diseases and Disorders Research	001	1	1/19/2022	NEW	-$3,444
2022	2022	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Oral Diseases and Disorders Research	000	1	12/30/2021	NEW	$741,782
2022	2022	UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER OF SAN ANTONIO	7703 FLOYD CURL DR	SAN ANTONIO	TX	78229	BEXAR	USA	Oral Diseases and Disorders Research	002	1	9/20/2022	SUPPLEMENT FOR EXPANSION	$265,280
														Subtotal = $1,003,618

Grand Total All Awards = $3,162,890

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Functional peripheral and central vagal neural circuits of interoception inhibiting pain

Award Number: R01DE031477

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 01/01/2022

PERIOD OF PERFORMANCE END DATE: 12/31/2026

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