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The role of the lateral habenula in central pain and itch processing

Award Number: F31DE029361
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 11/01/2021
PERIOD OF PERFORMANCE END DATE: 07/31/2022

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The role of the lateral habenula in central pain and itch processing - Project Summary Although acute pain and acute itch sensations serve essential protective functions, certain pathological conditions can lead to debilitating chronic pain and chronic itch disorders that greatly impair quality of life. A better understanding of the neural mechanisms underlying pain and itch is essential for developing better therapeutic options for these disorders. Despite recent advances in our knowledge of peripheral pain and itch differentiation, a few functional imaging studies in humans have shown significant overlap between brain regions associated with pain and itch activity, raising questions as to how these sensory modalities are distinguished in the central nervous system (CNS). At present, the circuitry and cellular mechanisms by which pain and itch are similarly or differently processed in the CNS remain unclear. My preliminary results show strong activation of the lateral habenula (LHb), a region important for integrating negative valence information and driving motivated behaviors, in response to trigeminal pain or itch stimuli. Given the distinct stereotyped behaviors produced by pain and itch sensation, the LHb may play an important role in differentiating pain and itch. Alternatively, the LHb may process shared aversive signals associated with both sensations. Nevertheless, the precise circuits in which the LHb functions to shape pain and itch sensory experiences have not been defined. In the proposed work, I will determine the divergent or convergent functional role of the LHb in trigeminal pain and itch pathways. In Aim 1, I will determine whether trigeminal pain- and itch-activated LHb populations are shared or divergent by comparing co-expression of known molecular markers in the LHb. To further establish the extent of overlap or segregation between these populations, I will combine genetic trapping of activated neurons and histological techniques to directly compare pain and itch activation in the same LHb. In Aim 2, I will use viral tracing to determine the presynaptic inputs and downstream projections of pain- and itch-activated LHb neurons, and gain insight into the differences and/or similarities between neural pathways mediating pain and itch sensations. Lastly, in Aim 3, I will determine the functional role of the LHb in mediating pain and itch sensations/behaviors. Specifically, I will investigate the dynamic activity of pain- and itch-activated LHb neurons by using in vivo calcium imaging. I will also test the requirement of these LHb populations for pain/itch sensation and behavior by selectively ablating them. The anticipated results of this proposal will improve our understanding about how pain and itch sensations are divergently or convergently processed in the CNS. Given the known role of the LHb, my work may reveal novel insight into the neural circuits mediating the affective-motivational dimensions of pain and itch.


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: 2023 ( Subtotal = -$14,920 )
2023	2022	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Oral Diseases and Disorders Research	000	3	5/15/2023	SUPPLEMENT FOR EXPANSION	-$14,920
														Subtotal = -$14,920

Issue Date FY: 2022 ( Subtotal = $26,316 )
2022	2022	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Oral Diseases and Disorders Research	001	3	11/3/2021	SUPPLEMENT FOR EXPANSION	$26,316
2022	2021	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Oral Diseases and Disorders Research	000	3	11/2/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $26,316

Issue Date FY: 2021 ( Subtotal = $9,144 )
2021	2021	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Oral Diseases and Disorders Research	000	3	7/23/2021	NON-COMPETING CONTINUATION	$9,144
														Subtotal = $9,144

Issue Date FY: 2020 ( Subtotal = $33,532 )
2020	2020	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Oral Diseases and Disorders Research	000	2	7/10/2020	NON-COMPETING CONTINUATION	$33,532
														Subtotal = $33,532

Issue Date FY: 2019 ( Subtotal = $45,816 )
2019	2019	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Oral Diseases and Disorders Research	001	1	8/28/2019	NEW	$0
2019	2019	TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE	3451 WALNUT ST STE 440A	PHILADELPHIA	PA	19104	PHILADELPHIA	USA	Oral Diseases and Disorders Research	000	1	8/28/2019	NEW	$45,816
														Subtotal = $45,816

Grand Total All Awards = $99,888

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The role of the lateral habenula in central pain and itch processing

Award Number: F31DE029361

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 11/01/2021

PERIOD OF PERFORMANCE END DATE: 07/31/2022

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