Transcutaneous conditioning electrical stimulation alters the cold detection threshold

Many patients with small fiber neuropathy experience elevated pain sensation for cold stimuli, and the pathophysiology is highly unknown. Therefore, the aim of this study was to evaluate a new method for probing the peripheral cold-sending fibers by combining electrical and thermal stimulation. The cold and warm detection thresholds (CDT and WDT) were measured in 17 healthy participants under the conditions with and without electrical conditioning stimulation. The electrical stimulation was tested using both 4 and 250 Hz at 50% of the electrical perception threshold. A small area cathode electrode was used for the electrical stimulation, and a thermode was placed on top of the electrode to estimate the thermal thresholds. Two-way RMANOVA was performed to analyze the results. The CDT decreased from 26.8°C (SD -4.1, +2.5, log-transformed) to 25.8°C (SD -4.9, +2.9, log-transformed) by the conditioning electrical stimulation (P = 0.006). The mean WDT was 41.6°C (SD -3.0, +4.1, log-transformed) without and 40.7°C (SD -3.1, +4.6, log₁₀-transformed) with conditioning electrical stimulation (P = 0.12). No significant main effect was found for the frequency of electrical stimulation for the two thermal thresholds. Conditioning electrical stimulation significantly altered the CDT but not the WDT, which can be explained by the small cathode's preferential activation of Aδ fibers to a greater extent than C fibers since the cold, innoxious sensation is mainly mediated by Aδ fibers and the warm sensation by C fibers. Combining thermal and electrical stimulation may, in the future, be used for probing cold-sensing fiber excitability, but further studies are necessary to validate the results.NEW & NOTEWORTHY A novel approach is evaluated for probing peripheral cold-sensing fiber by using electrical stimulation's large variety of protocols in combination with activation of the fiber by thermal stimulation to ensure selective activation of the cold-sensing fibers. The results showed that the cold detection threshold could be altered by electrical stimulation, but no significant differences were found for warm temperatures or different frequencies of conditioning electrical stimulation. The result was promising, but further studies are needed.