# Spatiotemporal Coding in the Pain Circuit Along the Spine-brain Continuum

> **NIH NIH R01** · CLEVELAND CLINIC LERNER COM-CWRU · 2021 · $89,579

## Abstract

PROJECT SUMMARY
Understanding the cellular biology and neurophysiology of sensory processing in the spinal cord is
fundamental to advancing medical intervention in the treatment of chronic and acute pain conditions. The
current understanding of the neurophysiology of spinal cord circuitry is founded on experimental single-unit
electrophysiology on anesthetized animals and in-vitro studies, but limited data exist from in-vivo functional
circuitry of sensory signals. Part of the challenge to such experimentation has been the limited capacity for
monitoring electrophysiologic signals in awake animals and inducing reliable activation of pain fibers.
Consequently, the activity of specific neuronal subtypes in propagating excitatory and inhibitory signals
involved in the transmission of pain signals remains unknown in-vivo. Recently, we have developed a pain
detection assay consisting of a lick behavior in response to optogenetic activation of predominantly nociceptive
peripheral afferent nerve fibers in head-restrained transgenic mice expressing Channelrhodopsin 2 (ChR2) in
transient receptor potential cation channel subfamily V member 1 (TRPV1) containing neurons. In this model,
mice are trained to provide lick reports to the detection of light-evoked nociceptive stimulation to the hind paw.
Our nociceptive lick-report detection assay enables a host of investigations into the millisecond, single-cell,
neural dynamics underlying pain processing in the central nervous system of awake behaving animals.
Further, we have developed a “backpack drive” to provide multi-site chronic extracellular recordings from
dorsal horn neurons derived from superficial laminas II-III. Unfortunately, such electrophysiology cannot be
used to determine cellular subclasses during recording. Here, we will focus on advancing our ability to record
cell-type-specific activity in the dorsal horn in response to light-activated TRPV1 containing neurons in the
periphery. We will develop a reliable method for achieving consistent GCaMP6-family expression in specific
neuronal cell types (e.g. CaMKII, PV) involved in the specific activation of pain signals through our optogenetic
stimulation experimental design. We will optimize a spinal optical window to perform awake Calcium imaging
during time-locked tactile input and characterize calcium dynamics in neuronal subtypes in the dorsal horn
during behavioral tasks. This work will establish a methodology to collect temporal dynamics of large classes of
neurons in the dorsal horn in response to time-locked, spatially-precise, and amplitude-modulated input in the
periphery leading to improved understanding of acute pain conditions.

## Key facts

- **NIH application ID:** 10205394
- **Project number:** 3R01NS108414-04S1
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** David Allenson Borton
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $89,579
- **Award type:** 3
- **Project period:** 2021-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10205394

## Citation

> US National Institutes of Health, RePORTER application 10205394, Spatiotemporal Coding in the Pain Circuit Along the Spine-brain Continuum (3R01NS108414-04S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10205394. Licensed CC0.

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