# Spinal Cord Nociceptive Circuits that Deliver Outputs to the Brain to Initiate Pain

> **NIH NIH R01** · HARVARD MEDICAL SCHOOL · 2020 · $3,264,750

## Abstract

Abstract
Our goal is to generate a predictive model of the spinal cord nociceptive circuits that underlie the initiation of
pain perception and behavior. Nociceptive signals are conveyed from the periphery to the spinal cord dorsal
horn via highly specialized primary sensory neuron subtypes. These sensory neurons, as well as descending
modulatory neurons, form synapses upon an array of morphologically and physiologically distinct classes of
dorsal horn interneuron and projection neurons. The ascending output signals from the superficial dorsal horn
to the brain are conveyed by neurons of the anterolateral tract (ALT), which project to the thalamus,
periaqueductal gray, superior colliculus, lateral parabrachial nucleus, and ventral brainstem. The goal of this
project is to define how critical sensory transformations and computations are achieved by these dorsal horn
nociceptive circuits and how ALT circuit outputs are conveyed with spatial and contextual precision to recipient
brain regions to drive pain and changes in behavior, as well as gain an understanding of the mechanisms
responsible for the transition of acute to chronic pain. The premise behind this work is that predictive models of
spinal cord nociceptive circuits that underlie the initiation of pain perception and behavior require: 1) defining
circuit output neurons and their specific tuning properties; 2) understanding the logic of primary sensory neuron
input onto these ALT output neurons; 3) determining the contributions of ALT output neuron classes to
reactions to noxious and innocuous stimuli and determining how this changes in disease conditions, and; 4)
defining the brain targets of dorsal horn nociceptive circuit output populations. This project will use novel ALT
pathway genetic tools in mice to identify, record from, silence and activate specific ALT subpopulations, and
physiological, anatomical, and novel, quantitative behavioral approaches to define the pivotal output channels
of distinct dorsal horn nociceptive circuits that underlie the perception of pain and its associated affective and
behavioral responses. Findings of the proposed work will establish the core logic of dorsal horn nociceptive
circuitry to lay a foundation for defining novel therapeutic opportunities for disrupting this circuitry to treat and
prevent chronic pain.

## Key facts

- **NIH application ID:** 10053529
- **Project number:** 1R01AT011447-01
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Jan Drugowitsch
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $3,264,750
- **Award type:** 1
- **Project period:** 2020-09-15 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10053529

## Citation

> US National Institutes of Health, RePORTER application 10053529, Spinal Cord Nociceptive Circuits that Deliver Outputs to the Brain to Initiate Pain (1R01AT011447-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10053529. Licensed CC0.

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