Background & Aims

The lack of a neuropathic pain biomarker poses a significant challenge in analgesic development. Silent in healthy subjects, C mechano-insensitive (CMi) fibers establish and maintain pain in the setting of peripheral neuropathy (PN) (1). Assessment of CMi fiber function is a promising biomarker of PN pain. However, these fibers are not easily assessable by traditional methods. We developed Diode Laser fiber selective stimulation (DLss) that triggers neurogenic axon reflex flare, revealing fiber-specific and selective stimulation of CMi fibers in humans, monkeys, and pigs. We also demonstrated that DLss may distinguuish painful from painless PN patients and reflects efficacy of blocking of CMi fibers by peripherally acting analgesics. We aim to demonstrate if DLss induced pain and detection thresholds of activation of C or A delta fibers as well as axon reflex flare can establish a biomarker for response to peripherally acting analgesics.

Methods

We evaluate DLss as a response biomarker for analgesic efficacy in PN pain patients, using a topical lidocaine patch (ZT-Lido) in a double-blind crossover study. The detection and pain thresholds of C and A delta fibers are evoked by DLss method using Lass-10M (LasMed, Mountain View, CA)(2,3), and CMi mediated axon reflex flare response area is recorded by Speckle Imager (Perimed, Sweden). Neuropathy phenotyping included the Utah Early Neuropathy Scale, nerve conduction studies and skin biopsy for IENFD. Participants reported chronic pain daily using the Visual Analog Scale (VAS). Study Design: 5 visits – baseline (visit 1), 7 day lead in (visit 2), 7 days of active/placebo patch (12 hrs/day), re-assessment (visit 3), 7-day washout, re-assessment (visit 4), and 7 days of active/placebo patch followed by re-assessment (visit 5).

Results

The lidocaine patch interval reduced VAS compared to placebo, significantly increased DLss pain and detection thresholds, and markedly suppressed axon reflex flare area.

Conclusions

Preliminary data suggest modulation of DLss-induced thresholds and flare correlates with VAS modulation in this cross over treatment paradigm. Further PN recruitment is underway to validate DLss-based threshold and flare as a combined response biomarker.

References

1. Nemenov M.I., Singleton J.R., Premkumar L S. Role of Mechanoinsensitive Nociceptors in Painful Diabetic Peripheral Neuropathy. Curr Diabetes Rev. 2022;18(5):e081221198649.
2. Moeller-Bertram T., Schilling J. M., Backonja M. M., Nemenov M. I.
Sensory Small Fiber Function Differentially Assessed with Diode Laser (DL) Quantitative Sensory Testing (QST) in Painful Neuropathy (PN). Pain Medicine
2013; 14 (3): 417-421
3. Nemenov M.I., Alaverdyan H., Burk C., Roles K, Frey K., Yan Y., Kazinets G.,
Haroutounian S. Characterization of patients with and without painful peripheral
neuropathy after receiving neurotoxic chemotherapy: traditional
quantitative sensory testing vs C-fiber and A?-fiber selective diode
laser stimulation. J Pain. 2022 May;23(5):796-809.

Presenting Author

J. Robinson Singleton

Poster Authors

J. Robinson Singleton

MD

University of Utah

Lead Author

Miguel Numa

BSc

University of Utah

Lead Author

Cathy Revere

University of Utah

Lead Author

Mikhail Nemenov

PhD

LasMed LLC

Lead Author

Topics

  • Assessment and Diagnosis