476-P: Investigating C-Fiber Activation and Pain Sensitivity in Diabetic Sensorimotor Neuropathy with Transcutaneous Electrical Nerve Stimulation

Introduction & Objective: We aimed to assess C-fiber excitability via transcutaneous-electrical nerve stimulation (TENS) in diabetic sensorimotor neuropathy (DSPN) and its association with epidermal innervation and quantitative sensory testing. Pain perception was evaluated in glucose-tolerant humans (n=14) and patients with type 2 diabetes: no-DSPN (n=15), possible-DSPN (n=21), probable-DSPN (n=19), and confirmed-DSPN (n=11). Subsequent analysis compared patients with positive (n=17) and negative symptoms (n=16).

Methods: Slow depolarizing transcutaneous currents of low-intensity with 4 Hz sinusoidal stimulation profile and single 500 ms half sine wave pulses were used to stimulate C-fibers. Pain perception quantified using (0-10)-Numeric-Rating-Scale, detection/pain thresholds and pain-change-dynamics were assessed.

Results: Confirmed-DSPN had diminished pain perception (1.72±0.50 vs 4.98±0.46), elevated detection (0.19±0.04 vs 0.05±0.01) and pain thresholds (0.28±0.04 vs 0.1±0.01) and reduced pain habituation compared to the control group. Elevated pain perception (pos:7.32±0.72 vs neg:3.81±0.98) and lowered detection/pain thresholds (pos:0.24±0.04 vs neg:0.13±0.03) were shown in the positive symptoms group compared to the negative symptoms group (p<0.05). Over 50% of patients with DSPN experience elevated pain with electrical stimuli in regions with reduced heat pain sensitivity, while less than 6% show similar responses in areas with diminished mechanical pain sensitivity indicating axonal degeneration.

Conclusions: Our results suggest that DSPN proceeds via differential transductional disruption towards denervation. TENS results, influenced by positive symptoms, confirm C-fibers' role for the clinical burden of DSPN. TENS offers further insights into DSPN's natural course, aiding high-risk patient identification and guiding interventions.