# Optimization of Non Invasive Brain Stimulation for Diabetic Neuropathic Pain

> **NIH NIH R44** · HIGHLAND INSTRUMENTS, INC. · 2021 · $388,328

## Abstract

Abstract. Diabetic neuropathic pain (DNP) is one of the most common and difficult to treat complications of
diabetes [1, 2]. Current therapies [3-10] do not directly address the fact that pain sensation is processed in the
brain [10-13] and most act at the neuropathy site (i.e., in the periphery), although DNP patients also have a
central pain component due to their injury [10-13]. DNP symptomatology correlates with chronic pain induced
changes in brain activity and/or structure [13-19]. Non-Invasive Brain Stimulation (NIBS) has been successfully
applied for the treatment of chronic pain in some disease states, where treatment induced changes in brain
activity revert maladaptive plasticity associated with the perception/sensation of chronic pain [20-23]. However,
the most common NIBS methods, Transcranial Magnetic Stimulation (TMS) and Transcranial Direct Current
Stimulation (tDCS), have shown limited, if any, efficacy in treating neuropathic pain and DNP [12, 24-30]. It has
been postulated that limitations in these techniques' focality, penetration, and targeting control limit their
therapeutic efficacy [31-35]. Electrosonic Stimulation (ESStim™) is an improved NIBS modality that overcomes
the limitations of other technologies by combining independently controlled electromagnetic and ultrasonic
fields to focus and boost stimulation currents via tuned electromechanical coupling in neural tissue [36]. This
proposal is focused on evaluating whether our noninvasive ESStim system can effectively treat DNP. First in
Phase I, to assess the feasibility of the proposed work, we will follow 20 DNP patients after giving a fixed dose
of ESStim for 5 consecutive days, 20 min/day (10 SHAM ESStim, 10 ESStim™). We will administer a battery
of safety, pain, quantitative sensory testing (QST), motor function, and global self-assessments (e.g., QOL),
and actigraphy measures in the patients, evaluated over the treatment period and for at least six weeks
following the last treatment session. Next in Phase II, we will follow 40 DNP patients (20 ESStim, 20 SHAM)
after giving a fixed dose of stimulation for 5 consecutive days, 20 min/day, followed by three weeks of bi-
weekly stimulation, 20 min/day (11 total stimulations). We will evaluate these patients with the same battery of
assessments validated in Phase I, and compare the efficacy of the tested interventions for at least eight weeks
following the last treatment session. In parallel with the DNP treatments, we will build MRI derived models of
the stimulation fields in the heads (electric and acoustic field models) of the DNP patients to calculate the
stimulation field characteristics at the brain target sites. Multivariate linear and generalized linear regression
models will then be built and evaluated to predict the DNP patient outcomes related to pain, physical function,
and psychosocial assessments as a function of baseline disease characteristics and the MRI based dosing
models. The computational work will be...

## Key facts

- **NIH application ID:** 10246692
- **Project number:** 4R44DK117710-02
- **Recipient organization:** HIGHLAND INSTRUMENTS, INC.
- **Principal Investigator:** Laura Dipietro
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $388,328
- **Award type:** 4N
- **Project period:** 2020-12-10 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10246692

## Citation

> US National Institutes of Health, RePORTER application 10246692, Optimization of Non Invasive Brain Stimulation for Diabetic Neuropathic Pain (4R44DK117710-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10246692. Licensed CC0.

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