# Multisite adaptive brain stimulation for multidimensional treatment of refractory chronic pain

> **NIH NIH UH3** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $1,528,807

## Abstract

PROJECT SUMMARY
A diverse array of chronic pain syndromes are refractory to almost all treatment but involve pathological activity
in similar brain regions. This suggests therapeutic potential for deep brain stimulation (DBS) for refractory pain
disorders, but despite early promise, long-term efficacy is lacking. Current DBS devices are limited in anatomical
reach, targeting only a subset of the distinct brain regions known to be important. Further, DBS therapy is bluntly
applied in an “open-loop,” continuous fashion without regard to underlying physiology. As a result of these
shortcomings, DBS for pain is often ineffective or shows diminished effect over time. Loss of therapeutic effect
may be due to nervous system adaptation or a failure of stimulation to accommodate patient- specific dynamics
of pain processing. DBS could be significantly improved by seeking individually optimized brain targets or by
using neural biomarkers of pain to selectively control stimulation when it is needed (“closed-loop” DBS). Better
brain targets would also address the different dimensions of pain such as somatosensory (location, intensity and
duration), affective (mood and motivation) and cognitive (attention and memory). The main goal of this study is
to test the feasibility of personalized targeting of brain regions that support multiple pain dimensions and to
develop new technology for “closed-loop” DBS for pain. We will develop data-driven stimulation control
algorithms to treat chronic pain using a novel device (Medtronic Summit RC+S) that allows longitudinal
intracranial signal recording in an ambulatory setting. By building this technology in an implanted device, we will
tailor chronic pain DBS to each patient and advance precision methods for DBS more generally.
 Beginning with an inpatient trial period, subjects with various refractory chronic pain syndromes will
undergo bilateral surgical implant of temporary electrodes in the thalamus, anterior cingulate, prefrontal cortex,
insula and amygdala. These regions have been implicated in the multiple dimensions of pain. The goal of the
trial period is to identify candidate biomarkers of pain and optimal stimulation parameters for each individual, and
to select subjects who show likelihood to benefit from the trial. A subgroup of 6 such patients will then proceed
to chronic implantation of up to 3 “optimal” brain regions for long-term recording and stimulation. We will first
validate biomarkers of low- and high-pain states to define neural signals for pain prediction in individuals (Aim
1). We will then use these pain biomarkers to develop personalized closed-loop algorithms for DBS and test the
feasibility of performing closed-loop DBS for chronic pain in weekly blocks (Aim 2). We will then assess the
efficacy of closed-loop DBS algorithms against traditional open-loop DBS or sham in a double-blinded cross-
over trial (Aim 3) and measure mechanisms of DBS tolerance. Our main outcome measures will be a combin...

## Key facts

- **NIH application ID:** 10239201
- **Project number:** 5UH3NS115631-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Prasad Shirvalkar
- **Activity code:** UH3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,528,807
- **Award type:** 5
- **Project period:** 2019-09-30 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10239201

## Citation

> US National Institutes of Health, RePORTER application 10239201, Multisite adaptive brain stimulation for multidimensional treatment of refractory chronic pain (5UH3NS115631-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10239201. Licensed CC0.

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