# Autophagy and Neuropathic Pain

> **NIH NIH R21** · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2020 · $425,000

## Abstract

ABSTRACT
 The long-term goal of this project is to identify how diet influences neuropathic pain. Painful diabetic
neuropathy (PDN) is a common symptom of diabetes in which poor glucose regulation causes sensory afferent
dysfunction, affecting 50% of diabetic patients within 25 years of their diagnosis. However, the mechanism by
which dietary hyperglycemia causes sensory neuron dysfunction and eventual neurodegeneration is not
completely known. This represents a significant gap in knowledge and an important unmet need, since type-2
diabetics are expected to represent the largest neuropathic pain population by 2030. Preliminary studies indicate
that hyperglycemic conditions disrupt sensory neuronal autophagy, a process by which organelles and proteins
are metabolized and recycled. Multiple studies in central nervous system structures have identified that
autophagy is critical to neuronal health, such that inhibition of this process causes neurodegeneration. The
objective of this proposal is to identify that hyperglycemic inhibition of autophagy produces painful diabetic
neuropathy symptoms. Based on our preliminary findings and existing literature, our central hypothesis is that
hyperglycemia inhibits autophagy in sensory neurons. This hypothesis will be addressed through two specific
aims that (1) quantify the contribution of AMPK/mTOR signaling to hyperglycemic inhibition of autophagy and
(2) determine whether increasing autophagy improves PDN in type-2 diabetes. The proposed study is innovative
because it utilizes transgenic technology to manipulate autophagy in sensory neurons of rodents exposed to a
translationally relevant model of type-2 diabetes. The contribution of this research is significant because it
advances our understanding of mechanisms that contribute to type-2 diabetic neuropathic pain and perhaps
other neuropathic conditions.

## Key facts

- **NIH application ID:** 10123243
- **Project number:** 1R21NS120276-01A1
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
- **Principal Investigator:** NATHANIEL Aaron JESKE
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $425,000
- **Award type:** 1
- **Project period:** 2020-09-30 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10123243

## Citation

> US National Institutes of Health, RePORTER application 10123243, Autophagy and Neuropathic Pain (1R21NS120276-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10123243. Licensed CC0.

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