# Novel Path to Chronic Sensorimotor Dysfunction and Treatment for Chemotherapy

> **NIH NIH R01** · GEORGIA INSTITUTE OF TECHNOLOGY · 2020 · $305,907

## Abstract

Abstract
Chemotherapy is often accompanied by neuropathic sensory disorders that can limit or end treatment and
cause long-term disability. Current research supports axon degeneration and hyperexcitability as underlying
mechanisms. However, our recent research reveals an additional, absolutely novel mechanism having the
potential to account for loss of patient function in chemotherapy-related neuropathy. We obtained in vivo
electrophysiological measures which showed functional impairment of neuronal signaling from sensory and
motor neurons in rats several weeks after receiving a clinically-relevant regimen of oxaliplatin (OX)
chemotherapy. Hypo-excitability was consistently expressed as conspicuous failure to sustain firing in
response to fixed levels of stimulation. The specificity of this defect, which leaves transient firing unaffected,
suggests that OX treatment may impair sodium persistent inward currents (NaPIC) in sensory and motor
neurons. Recent findings published in our lab promote this notion by showing that pharmacological block of
NaPIC mimics the effect of OX on sustained firing. While our findings isolate chronic effects of chemotherapy
on neuronal excitability, there is no chemotherapy without cancer. Cancer and OX therapy may act
synergistically on common signaling pathways (e.g. oxidative and inflammatory) to produce neuronal hypo-
excitability. The possibility of an interaction between cancer and OX therapy gains excitement from our
preliminary reports that discovered sensory and motor neuron hypo-excitability is significantly amplified in rats
with colorectal cancer. Here we propose incisive tests of our working hypothesis that OX treatment chronically
impairs static neuronal signaling by reducing NaPIC in a rat model of cancer. We will measure the firing
behavior of sensory and motor neurons via in vivo electrophysiological studies of cancer rats treated with OX,
in order to achieve the following four specific aims: 1) test the hypothesis that interactions with cancer-related
processes exacerbate chemotherapy-induced hypo-excitability in sensory and motor neurons; 2) test the
hypothesis that chronic defects in repetitive firing by motor neurons result from an OX-induced decrease in
persistent inward current; 3) develop therapy that normalizes firing of sensory and motor neurons in rats
treated for cancer with OX; 4) identify factors related to the development of hypo-excitability induced by OX in
a rat model of colorectal cancer. Successful accomplishment of these studies will: 1) determine for the first
time in the CIPN field, of the extent to which chronic deficits in neuronal excitability arise from OX therapy,
colorectal cancer, and their combination; 2) identify biophysical mechanisms underlying firing deficits of a CNS
neuron after OX treatment; 3) develop pre-clinically a viable therapy for rescuing neurons from OX-induced
firing deficits; 4) take the first step forward in understanding the pathogenesis of OX-induced h...

## Key facts

- **NIH application ID:** 9986707
- **Project number:** 5R01CA221363-03
- **Recipient organization:** GEORGIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Timothy C Cope
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $305,907
- **Award type:** 5
- **Project period:** 2018-09-13 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9986707

## Citation

> US National Institutes of Health, RePORTER application 9986707, Novel Path to Chronic Sensorimotor Dysfunction and Treatment for Chemotherapy (5R01CA221363-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9986707. Licensed CC0.

---

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