# Sensorimotor training and cortical mechanisms of pain after spinal cord injury

> **NIH VA I01** · VA SAN DIEGO HEALTHCARE SYSTEM · 2021 · —

## Abstract

In addition to impairment of motor, autonomic, and sensory functions, severe pain is highly prevalent in
patients after spinal cord injury (SCI) including active military personnel and veterans. This project aims to
better understand the mechanisms and changes underlying the development of central neuropathic pain after
SCI and test a novel strategy for controlling the pain. Because SCI causes an initial deprivation of afferent
input to the somatosensory cortex and subsequent hyperexcitability, we hypothesize that this transition in
cortical activity is driven by excessive homeostatic compensation to the initial loss of activity of SCI and that
enhancing cortical activity will suppress this overcompensation and control pain. Our previous work has
characterized the onset and maintenance of chronic central neuropathic pain in a mouse model of contusion
injury. Our preliminary data also show that sensory cortical activity is initially decreased after a transient spinal
cord ischemia followed by hyperactivity paralleling the onset of pain behavior. This hyperactivity and the
associated pain behavior can be diminished by optogenetic stimulation of somatosensory cortex early after
injury. In addition, we have shown that treadmill training can prevent the development and partially reverse
pain-associated behavior in mice. We now aim to characterize in detail changes in somatosensory cortical
activity after traumatic SCI in mice using patch-clamp recording and in vivo two-photon imaging of neuronal
activity in transgenic mice. We also aim to determine whether modulating cortical activity by optogenetics,
electrical stimulation or somatosensory training or a combination can modulate cortical hyperactivity after SCI
and thereby ameliorate neuropathic pain. Based on the homeostatic plasticity hypothesis, this project will
challenge the conventional assumption that hyperexcitability of neuronal circuits can only be modified by
directly blocking excitation or increasing the activity of inhibitory circuits. Thereby, we will advance our
understanding of the development and maintenance of chronic pain after SCI, identify cortical mechanisms
underlying the development of chronic pain, and validate a novel activity-enhancing therapeutic strategy that
can be translated into novel pharmacological and rehabilitative treatments that interfere with homeostatic
plasticity for a comprehensive pain management in active military and veterans.

## Key facts

- **NIH application ID:** 10056997
- **Project number:** 5I01RX002840-04
- **Recipient organization:** VA SAN DIEGO HEALTHCARE SYSTEM
- **Principal Investigator:** ARMIN BLESCH
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2018-11-01 → 2022-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10056997

## Citation

> US National Institutes of Health, RePORTER application 10056997, Sensorimotor training and cortical mechanisms of pain after spinal cord injury (5I01RX002840-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10056997. Licensed CC0.

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