# Discovery and Validation of a Novel Response Biomarker Signature for Painful Peripheral Neuropathy

> **NIH NIH R61** · LASMED, LLC · 2023 · $502,796

## Abstract

Project Abstract
 The purpose of this R61/R33 application is to optimize a novel response biomarker signature of peripheral
ongoing neuropathic pain (ONP) and provide its analytical and initial clinical validation as an FDA Biomarkers
EndpointS and other Tools (BEST) categorical Response biomarker for efficacy of peripherally acting pain
therapy. Spontaneous peripheral ONP is a frequent presenting symptom, and often the most debilitating feature
of peripheral sensory neuropathy, severely impacting quality of life. Painful peripheral neuropathy (PN), whether
idiopathic, or associated with chemotherapy (chemotherapy induced polyneuropathy) and other drugs, diabetes,
metabolic syndrome or hereditary disease afflicts 6-10% of the US population. There is a lack of effective
treatment leading to opioid prescription in most PN patients, with resulting morbidity. Development of
medications that reduce spontaneous peripheral nociceptor transmission is hindered by lack of a practical
Response biomarker specific for these fibers. We have preliminary evidence for a novel peripheral ONP
biomarker signature based on assessment of C and Aδ nociceptors using a diode laser to selectively stimulate
these fibers (DLss). Spontaneous activity of cutaneous C fibers, mainly C mechano-insensitive fibers (CMi), are
responsible for mediation of peripheral ONP. DLss allows assessment of spontaneously active CMi fiber-
mediated neuropathic pain across cutaneous depth, while assessment of Aδ fibers provides a surrogate measure
of PN distal axonal loss. DLss also evokes CMi mediated cutaneous vasodilatative flare, a specific, objective
measure of CMi activation that can be quantified. We propose to develop DLss measures as a novel BEST
defined Response biomarker based on its specificity for peripheral origin of neuropathic pain. We hypothesize
that an optimized DLss measure combining CMi: Aδ response ratio and flare will significantly correlate with
change in reported neuropathic pain intensity in peripheral ONP patients, following treatment with peripherally
acting neuropathic pain medications.
 We plan to confirm that DLss measures are significantly correlated with extent of response to pain treatment
using a topical lidocaine patch. The R61 will perform a four part double-blind randomized crossover study
transitioning from a pretreatment baseline phase, to randomized treatment with either lidocaine or an identical
placebo patch, washout, and alternate arm. DLss measures will be obtained before and after each phase. Twice
daily report of pain using a visual analogue scale will track severity of ongoing spontaneous pain in participants.
The hybrid biomarker will distinguish between placebo and active treatment arms, will significantly correlate with
extent of neuropathic pain reduction during lidocaine, but will not change during the placebo phase or no-
treatment lead in. If preset G/No-Go criteria are met, the subsequent R33 validation will then compare lidocaine
patch and...

## Key facts

- **NIH application ID:** 10677537
- **Project number:** 5R61NS122298-02
- **Recipient organization:** LASMED, LLC
- **Principal Investigator:** Mikhail I. Nemenov
- **Activity code:** R61 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $502,796
- **Award type:** 5
- **Project period:** 2022-09-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10677537

## Citation

> US National Institutes of Health, RePORTER application 10677537, Discovery and Validation of a Novel Response Biomarker Signature for Painful Peripheral Neuropathy (5R61NS122298-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10677537. Licensed CC0.

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