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Transcutaneous electrical nerve stimulation (TENS) is a modality commonly used in pain management.This study investigated the hypoalgesic effects of alternating-frequency TENS (4 Hz for 3 s/110 Hz for 3 s) on pressure pain threshold (PPT).Two-hundred and eight healthy, pain-free volunteers (19 to 59 y old; 104 males, 104 females) were randomized to 8 groups: 6 active TENS groups, placebo, and control (n=26 per group). Parameter combinations were such that alternating-frequency TENS was combined with different levels of intensity “low” (strong but comfortable) or “high” (strong and uncomfortable but not painful). TENS was administered either at the forearm (segmental stimulation), at the ipsilateral leg (extrasegmental stimulation), or at both sites (dual-site stimulation) for 30 minutes and monitored for 30 further minutes. PPT measurements were taken bilaterally from the mid-point of first dorsal interosseous muscle, by an independent blinded rater, at baseline and at 6 subsequent 10-minute intervals. Square-root transformed data were analyzed using repeated measures analysis of covariance (baseline values and sex as covariates).Alternating-frequency TENS groups did not achieve significant hypoalgesic effects compared with placebo or control (P>0.05). The largest increase in PPT (from baseline) was 76.6 kPa with low-intensity segmental alternating frequency TENS at the 20-minute stimulation time point. This change from baseline is below a difference of 100 kPa that is considered to be a clinically meaningful change in hypoalgesia.The alternating-frequency setting does not result in large hypoalgesic effects such as those previously reported using fixed-frequency TENS.