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Modulation of autonomic function by affective pain pathways

Award Number: K99NS151133
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 08/01/2026
PERIOD OF PERFORMANCE END DATE: 07/31/2028

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Modulation of autonomic function by affective pain pathways - PROJECT SUMMARY Pain is a complex experience with both a sensory-discriminative component and an affective-emotional component. Affective-emotional states are intimately associated with bodily autonomic responses, and studies on human participants have identified consistent changes in autonomic nervous system (ANS) function during pain that correlate with subjective experience. My preliminary studies reveal similar changes in autonomic function in mouse models of acute, persistent, and chronic pain. We show that acute pain transiently increases heart rate and persistent and chronic pain are associated with prolonged periods of increased heart rate and decreased heart rate variability (HRV). The research goal of my proposal is to interrogate the role of the parabrachial-limbic circuit and the reciprocal connections between the central amygdala (CeA) and parabrachial nucleus (PBN) in the ANS responses observed during various pain states. In aim 1 I will determine how the activity of CeA neurons correlates with behavior and ANS responses and whether these relationships change as pain transitions from acute to chronic. I will use comprehensive computational analyses to delineate the relationship between fast time-scale neural activity and slower time-scale autonomic changes. In aim 2, I will test the hypothesis that different types of CeA neurons differentially modulate ANS responses and pain behaviors through projections to the PBN. Based on extensive preliminary data, I will focus on comparing and contrasting two non-overlapping CeA populations: the general anesthesia-activated CeAGA neurons and the Sst-expressing CeASst neurons in naïve mice and in pain models. My published work identified a population of neurons in the PBN (lPBNY1R neurons) that is persistently active during pain states. After transitioning to an independent position, I will test the hypotheses that lPBNY1R neuron activation drives persistent activation of CeASst neurons that then maintain a sympathetically-dominant ANS state by feeding back onto lPBNY1R neurons. CeAGA neurons break this positive feedback to restore ANS balance and suppress pain. Aim 3 will be carried out with a combination of cell-type- and projection-specific optogenetics and calcium imaging in naïve mice and in a model of chronic neuropathic pain. Completion of this project will expand our understanding of the importance of ANS function in pain as well as reveal potential targets for novel therapies for treating pain disorders. This project is also an essential step towards my long-term goal of becoming an independent researcher at a research institution. With guidance from my mentorship team, I will learn crucial technical, analytical, and professional skills by performing the proposed studies and disseminating my findings. This K99/R00 award will lay the foundation for my future research program investigating how bidirectional interactions between emotional and autonomic centers regulate 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: 2026 ( Subtotal = $129,168 )
2026	2026	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	7/30/2026	NEW	$129,168
														Subtotal = $129,168

Grand Total All Awards = $129,168

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Modulation of autonomic function by affective pain pathways

Award Number: K99NS151133

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 08/01/2026

PERIOD OF PERFORMANCE END DATE: 07/31/2028

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