Background & Aims

Clinical biomarkers accurately reflecting changes in ongoing neuropathic pain with therapy are currently lacking due to the inaccessibility of nerve fibers responsible for mediating pain through existing methods. In response, we developed a Diode Laser (DLss) technique selectively stimulating TRPv1 positive C or A? polymodal, as well as C mechano-insensitive fibers in the skin (1-7, 12). The efficacy of this technique has been validated in patients with peripheral diabetic and chemotherapy-induced pain, providing separation of painful and painless neuropathy (13, 14). The DLss method played a crucial role in preclinical development, aiding in the creation of new pain treatments in rodent, pig, and monkey models (8-11). This work presents test-retest reliability of the DLss for use in longitudinal clinical studies, with traditional QST as control, drawing on data from NIH/NINDS R61NS122298 project. Preliminary data on the size effect of topical lidocaine are also presented.

Methods

Fourteen healthy subjects, aged 25 to 67, without a history of neuropathic pain, musculoskeletal pain, chronic analgesic use, or diabetes, and three patients with peripheral painful neuropathy have been recruited. DLss sensory and pain thresholds for C-fiber and A?-selective protocols, as well as QST for WDT and HPT, were defined in 12 healthy subjects and 3 pain patients, following the methodology described in (14). Axon reflex flare induced by DLss (11) was measured using speckle imaging, considering flare area and intensity. In the first group, 9 healthy volunteers participated in all the listed evaluations twice, with testing days separated by at least 48 hours. In the second group, 3 healthy volunteers and 3 pain patients, after two tests, wore a 5% lidocaine patch on the foot dorsum for 12 hours, and then DLss and QST were repeated on the following day. Both DLss thresholds and flare protocols applied to the second group were optimized to increase test-retest reliability.

Results

For the first group of 9 healthy subjects, the Average Group Percent difference between testing sessions for C fiber pain threshold was 7.1%; for A? fiber detection thresholds, 11.0%; and for HPT by contact thermode, 6.6%. The application of optimized DLss protocols and decreasing baseline surface skin variability within sessions and between sessions allowed a decrease in the Average Group Percent difference for the second group of subjects, resulting in 2.7% for C pain thresholds and 4.7% for A? fiber detection thresholds. The Average Group Percent difference for flare area was 21%. However, flare area was significantly suppressed by lidocaine, with the Average Group Percent difference for flare between the first two tests and after lidocaine being > 45%.

Conclusions

The DLss thresholds show high test-re-test reliability, similar or better to that of commercial QST. CMi evoked axon reflex flare, while less reliable, shows even greater response to lidocaine. A combination of these DLss measures has potential as a biomarker correlate to neuropathic pain and analgesic efficacy.

Acknowledgement
NIH Heal Initiative/ NINDS grant # R61NS122298

References

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Presenting Author

J. Robinson Singleton

Poster Authors

Mikhail Nemenov

PhD,

LasMed LLC

Lead Author

Cathy Revere,

University of Utah

Lead Author

Michael Klukinov

MD

Stanford University

Lead Author

David C. Yeomans

PhD

Stanford University

Lead Author

J. Robinson Singleton

MD

University of Utah

Lead Author

Miguel Numa

BSc

University of Utah

Lead Author

Jordan Zhang

Stanford

Lead Author

Topics

  • Assessment and Diagnosis