# Development and Evaluation of Computerized Chemosensory-Based Orbitofrontal Networks Training for Treatment of Pain (CBOT-P)

> **NIH NIH R44** · EVON MEDICS, LLC · 2022 · $499,999

## Abstract

PHASE I/II (FAST/TRACK) ABSTRACT
 The Development and Evaluation of Computerized Chemosensory-Based Orbitofrontal Networks
Training for Treatment of Pain (CBOT-P) is a project to develop an effective, scalable, user-friendly, and home-
based neuromodulatory platform for broad-spectrum treatment of chronic pain conditions with associated
negative affect and cognitive impairments. Chronic pain (CP) affects 1.5 billion people globally, and causes
severe human suffering, disability, and high financial burden. Clinical and neuroscience studies show that CP
over time leads to shrinkage in the prefrontal cortex (PFC) regions and their deep brain connections critical to
emotion, motivation, and cognitive functions. As a result, more than 40% of CP patients suffer negative affect
(i.e., anxiety and depression), cognitive and decision-making problems and reduced drive. Chronic pain with
negative affect (CP-N) is more debilitating, harder to treat, costlier to payers and significantly more associated
with opioid use, overdose, and deaths. In a stakeholder value canvassing exercise CP sufferers and pain
doctors unanimously desire new non-invasive, home-based, safe, and effective interventions that can reduce
pain severity by more than 10%, suggesting that current treatments have limitations. Anterograde and
retrograde anatomical tracings have been used to demonstrate direct (monosynaptic) anatomical connection
between the OFC and the descending inhibitory pain nodes at the midbrain periaqueductal gray matter (PAG).
Transition to CP is marked by weakened modulation of the PAG-descending inhibition. Evon Medics, a small
business specializing in olfactory neurotherapeutics, developed an innovative chemosensory-based
orbitofrontal cortex (OFC) stimulation device, called CBOT-P, for home use, to increase OFC plasticity and
effect OFC-induced regulation of pain and negative affect. We now plan to refine this product for broad pain
conditions and quickly make it available to the population. OFC is the part of the prefrontal cortex that plays
key roles in multisensory integration, affect regulation, and decision-making. The lateral OFC, which is
consistently activated by pain, is connected to other cortical brain regions that process pain; and the medial
OFC, which networks with medial temporal affect networks, is engaged by mindfulness therapy for pain and
plays important role in positive affect and drive. Unfortunately, CP and opioid analgesics are associated with
OFC shrinkage, which amplifies pain through increased negative affect (NA) and cognitive impairment. The
success of CBOT-P in acute relief of NA and pain in our pilot studies is not surprising because single-pulsed
electrical stimulations with OFC-placed electrodes acutely relieved NA in humans in invasive deep brain
stimulation, and experimentally induced stimulation of the OFC in animal models and humans activates the
PAG to reduce pain sensitization. The CBOT-P uses Evon’s proprietary regimen of 10 od...

## Key facts

- **NIH application ID:** 10547925
- **Project number:** 1R44NS125745-01A1
- **Recipient organization:** EVON MEDICS, LLC
- **Principal Investigator:** Charles Chiedu Nwaokobia
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $499,999
- **Award type:** 1
- **Project period:** 2022-09-20 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10547925

## Citation

> US National Institutes of Health, RePORTER application 10547925, Development and Evaluation of Computerized Chemosensory-Based Orbitofrontal Networks Training for Treatment of Pain (CBOT-P) (1R44NS125745-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10547925. Licensed CC0.

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