# Neural Ice Technology for Treatment of Pain

> **NIH NIH R44** · BRIXTON BIOSCIENCES, INC. · 2024 · $998,787

## Abstract

Total knee arthroplasty (TKA) is one of the most performed orthopedic surgeries to relieve joint pain in patients with end-stage osteoarthritis (OA) or rheumatic arthritis (RA). In the US, over 700,000 TKA procedures are performed annually. To manage TKA pain patients are commonly prescribed opioids, contributing to a spiraling opioid epidemic. The misuse and addiction to opioids is a national public health crisis with an estimated economic burden of $78.5 billion per year. As opioid addiction is now a national health focus, novel non-opioid and non-pharmacological treatments for postoperative pain are a top scientific priority. There is an urgent need for a long-lasting, drug-free means of relieving post-TKA pain–which is the overall goal of this project. Cryoneurolysis is an opioid-sparing, perioperative intervention used to reduce postoperative pain. Current cryoneurolysis methods apply very low-temperature cryoprobes to freeze peripheral nerves, resulting in reversible and long-lasting pain relief. However, due to extremely cold temperatures (–88oC and below) in direct contact with a nerve and surrounding tissues, these methods are not nerve-selective nor easy to administer. They also are not injectable, making the treatments time-consuming and challenging to adopt in clinic. Our initial goal – an easier to use, injectable method of cryoneurolysis to reduce postoperative pain from TKA, significantly reducing or eliminating the use of opioids. 
We invented a novel injectable and nerve-selective cryoneurolysis method that overcomes the limitations of current options. Neural Ice™ can be injected around sensory peripheral nerves that transmit pain. We have shown in a rat model that injection of our ice-slurry, formulated to bring peri-nerve temperatures to around -5oC, extracts enough thermal energy to reversibly disrupt nerve structure and reduce pain sensation for up to 8 weeks without damage to surrounding tissue. At the end of 2023, we also completed an initial 16-patient feasibility study showing significant pain reduction response with no serious adverse events (See Significance). In response to these findings (pre-clinical and clinical) in October 2023 the FDA granted Brixton Breakthrough Designation. 
In Phase II, we seek to optimize a clinical use device that produces an injectable, biocompatible, and sterile ice slurry which meets the FDA requirements for an Investigative Device Exemption (IDE) for a pivotal efficacy trial. With our HEAL Phase I grant we generated single-use, terminally sterilized pre-filled syringes that contain on-demand injectable slurry for use at point-of-care facilities. In Phase II we seek to optimize our design for human use (ease, effectiveness, cost, etc.) and test for in-vivo biologic response in rat model. We will also establish manufacturing of human use system & prepare to submit pivotal trial IDE application to the FDA at the end of the funding period. If successful, our study will lead to the development...

## Key facts

- **NIH application ID:** 11006862
- **Project number:** 1R44AR084998-01
- **Recipient organization:** BRIXTON BIOSCIENCES, INC.
- **Principal Investigator:** Charles Sidoti
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $998,787
- **Award type:** 1
- **Project period:** 2024-08-21 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11006862

## Citation

> US National Institutes of Health, RePORTER application 11006862, Neural Ice Technology for Treatment of Pain (1R44AR084998-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11006862. Licensed CC0.

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