# Investigations into the Etiology of Phantom Limb Sensations and Phantom Limb Pain

> **NIH NIH R01** · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · 2022 · $538,968

## Abstract

Project Abstract
 Major limb amputation affects millions of people worldwide. Following amputation, all most all patients have
phantom limb sensations (PLS) and over 85% develop phantom limb pain (PLP). Despite its documented
existence for several hundred years, the etiology of PLP remains unknown. The three principal theories are
cortical reorganization, a mismatch between visual and proprioceptive feedback, and proprioceptive memory.
Experimental evidence demonstrates that cortical maps representing a limb within sensorimotor cortex
reorganize following limb amputation. A correlation exists between the amount of cortical reorganization in
upper extremity amputees and the severity of PLP. We have recently demonstrated that mirror therapy can
relieve PLP in unilateral lower extremity amputees, but the physiological basis remains unknown. Our principal
hypothesis is that, rather than simple cortical reorganization, rapid, but reversible changes, in addition to
delayed changes, occur in the cortical network connecting various brain regions, leading to the development of
PLS and PLP. We will assess whether dynamic changes in connectivity following upper limb deafferentation
and manifest as PLS or PLP with proprioceptive memories, what changes there are in cortical network
connectivity (using fMRI) to assess changes in brain activation patterns before and after visual feedback from
mirror therapy, and determine if differential mechanisms underlie rapid and delayed dynamic functional
changes in cortical networks following permanent forelimb deafferentation (amputation or brachial plexus nerve
cut) and transient inactivation (brachial plexus anesthesia) using a rodent model to mimic changes observed in
humans. These studies will not only enable us to better understand the physiological basis of the interaction of
the visual system, cortical reorganization and network connectivity, and the development of PLP but will also
contribute to the development of a functional measure of the response of PLP to treatment and may result in
the development of additional treatments for PLP for both female and male amputees.

## Key facts

- **NIH application ID:** 10476261
- **Project number:** 5R01HD094588-04
- **Recipient organization:** UNIVERSITY OF TENNESSEE HEALTH SCI CTR
- **Principal Investigator:** ROBERT S WATERS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $538,968
- **Award type:** 5
- **Project period:** 2018-09-17 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10476261

## Citation

> US National Institutes of Health, RePORTER application 10476261, Investigations into the Etiology of Phantom Limb Sensations and Phantom Limb Pain (5R01HD094588-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10476261. Licensed CC0.

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