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

> **NIH NIH F31** · UNIVERSITY OF PENNSYLVANIA · 2020 · $33,532

## Abstract

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.

## Key facts

- **NIH application ID:** 10021401
- **Project number:** 5F31DE029361-02
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Suna Li
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $33,532
- **Award type:** 5
- **Project period:** 2019-09-01 → 2021-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10021401

## Citation

> US National Institutes of Health, RePORTER application 10021401, The role of the lateral habenula in central pain and itch processing (5F31DE029361-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10021401. Licensed CC0.

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