The test-retest reliability of large and small fiber nerve excitability testing with threshold tracking

Hossein Pia; Zahra Nochi; Alexander Gramm Kristensen; Bernhard Pelz; Marcus Goetz; Jan-Niclas Hoeink; Anthony James Blockeel; André Mouraux; Andrea Truini; Nanna Brix Finnerup; Keith Geoffrey Phillips; Rolf-Detlef Treede; Hatice Tankisi

doi:10.1016/j.cnp.2023.03.003

The test-retest reliability of large and small fiber nerve excitability testing with threshold tracking

Clin Neurophysiol Pract. 2023 Mar 30:8:71-78. doi: 10.1016/j.cnp.2023.03.003. eCollection 2023.

Authors

Hossein Pia^{1

2}, Zahra Nochi², Alexander Gramm Kristensen^{1

2}, Bernhard Pelz³, Marcus Goetz³, Jan-Niclas Hoeink³, Anthony James Blockeel⁴, André Mouraux⁵, Andrea Truini⁶, Nanna Brix Finnerup^{2

7}, Keith Geoffrey Phillips⁸, Rolf-Detlef Treede⁹, Hatice Tankisi^{1

10}

Affiliations

¹ Department of Clinical Neurophysiology, Aarhus University Hospital, Denmark.
² Danish Pain Research Center, Department of Clinical Medicine, Aarhus University, Denmark.
³ MRC Systems GmbH, Heidelberg, Germany.
⁴ School of Physiology, Pharmacology & Neuroscience, University of Bristol, United Kingdom.
⁵ Institute of Neuroscience (IoNS), UCLouvain, Brussels, Belgium.
⁶ Department of Human Neuroscience, Sapienza University, Rome, Italy.
⁷ Department of Neurology, Aarhus University Hospital, Aarhus, Denmark.
⁸ Eli Lilly and Company, CIC Cambridge, MA, United States.
⁹ Neurophysiology Department, Medical Faculty Mannheim, University of Heidelberg, Germany.
¹⁰ Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.

Abstract

Objective: Standard nerve excitability testing (NET) predominantly assesses Aα- and Aβ-fiber function, but a method examining small afferents would be of great interest in pain studies. Here, we examined the properties of a novel perception threshold tracking (PTT) method that preferentially activates Aδ-fibers using weak currents delivered by a novel multipin electrode and compared its reliability with NET.

Methods: Eighteen healthy subjects (mean age:34.06 ± 2.0) were examined three times with motor and sensory NET and PTT in morning and afternoon sessions on the same day (intra-day reliability) and after a week (inter-day reliability). NET was performed on the median nerve, while PTT stimuli were delivered through a multipin electrode located on the forearm. During PTT, subjects indicated stimulus perception via a button press and the intensity of the current was automatically increased or decreased accordingly by Qtrac software. This allowed changes in the perception threshold to be tracked during strength-duration time constant (SDTC) and threshold electrotonus protocols.

Results: The coefficient of variation (CoV) and interclass coefficient of variation (ICC) showed good-excellent reliability for most NET parameters. PTT showed poor reliability for both SDTC and threshold electrotonus parameters. There was a significant correlation between large (sensory NET) and small (PTT) fiber SDTC when all sessions were pooled (r = 0.29, p = 0.03).

Conclusions: Threshold tracking technique can be applied directly to small fibers via a psychophysical readout, but with the current technique, the reliability is poor.

Significance: Further studies are needed to examine whether Aβ-fiber SDTC may be a surrogate biomarker for peripheral nociceptive signalling.

Keywords: Motor nerve excitability testing; Pain biomarker; Perception threshold tracking; Sensory nerve excitability testing; Test–retest reliability.