# The Role of Distinct Dorsal Column Nuclei Outputs in Persistent Pain

> **NIH NIH K99** · RUTGERS, THE STATE UNIV OF N.J. · 2024 · $130,610

## Abstract

Project Summary/Abstract
Touch-evoked pain is a hallmark of persistent pain, making it crucial to understand how supraspinal touch
pathways contribute to the different aspects of pain. The dorsal column nuclei (DCN) in the brainstem receives
direct input from touch sensory neurons. Various non-specific manipulations such as ablation, electrical
stimulation, and pharmacology, have implicated the DCN in both transmitting and reducing touch-evoked pain.
While these manipulations highlight 2 opposing roles for the DCN, as a mediator or inhibitor of touch-evoked
pain, the mechanisms underlying these opposing roles remain unknown. The functional relevance of touch
processing by the DCN is defined by its output connectivity with effector structures throughout the brain. Two
important regulators of pain behavior, the ventral posterolateral thalamus (VPL) and ventrolateral periaqueductal
gray (vlPAG), receive input from the DCN. The VPL plays an important role in touch and pain perception, while
the vlPAG is part of a descending pain suppression circuit. My central hypothesis is that the dorsal column nuclei
(DCN) shape our central representation of touch through two functionally distinct pathways to the thalamus and
the periaqueductal gray. Disruption of the balance between these pathways following injury allows touch stimuli
to engage ‘pain’ pathways and promote touch-evoked pain. To test this hypothesis, I will employ a powerful
combination of tools to determine the mechanisms underlying altered touch signaling following neuropathic injury
and simultaneously image Ca2+ activity and optogenetically manipulate distinct neural populations to determine
how divergent projections to the VPL and vlPAG uniquely contribute to the sensory, affective, and motivations
components of pain behavior. During the mentored K99 phase, my career development and training will be
supervised by my mentors Drs. Abraria (Rutgers), Aston-Jones (Rutgers), and Stuber (University of
Washington). I will also receive additional support from Drs. Basbaum (UCSF), Abdus-Saboor (Columbia), Tao
(Rutgers), Margolis (Rutgers), and Azim (Salk). These mentors possess expertise in viral and optogenetic circuit
mapping, in-vivo Ca2+ imaging in freely behaving mice, machine-vision behavioral approaches to define how
neural networks encode different aspects of behavior in health and disease. During the independent R00 phase,
I will examine the postsynaptic targets of DCN projections within the VPL and vlPAG, studying how neural
ensembles in these regions encode the many facets of persistent pain behavior. Completing the proposed aims
will provide fundamental insight into how the DCN encodes tactile information and elucidate the circuits that
promote touch-evoked pain in persistent pain states. This career development award will provide conceptual and
technical training, as well as mentorship from renowned experts in the field of circuit neuroscience. The training
opportunities provided by the K99...

## Key facts

- **NIH application ID:** 10887232
- **Project number:** 1K99NS133476-01A1
- **Recipient organization:** RUTGERS, THE STATE UNIV OF N.J.
- **Principal Investigator:** Mark Gradwell
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $130,610
- **Award type:** 1
- **Project period:** 2024-07-15 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10887232

## Citation

> US National Institutes of Health, RePORTER application 10887232, The Role of Distinct Dorsal Column Nuclei Outputs in Persistent Pain (1K99NS133476-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10887232. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*