Transcutaneous electrical nerve stimulation (TENS) involves the application of electrode current through skin electrodes for pain control; it is a noninvasive modality that is commonly used by health care professionals to control both acute and chronic pain arising from a variety of conditions. Both high- and low-frequency TENS reduces hyperalgesia and pain through the release of endogenous opioids in the central nervous system. At the spinal level and the rostral ventral medulla there are different opioid receptors activated to produce analgesia with high or low frequency TENS. Low frequencies, usually below 10 Hz, activate µ-opioid receptors and high frequencies, above 50 Hz, activate δ-opioid receptors. Repeated stimulation of opioid receptors by repeated administration of morphine or opioid analgesics can lead to analgesic tolerance defined as a decrease in analgesic effectiveness with repeated use. In a similar way, repeated application of physical agents that reduce pain through release of endogenous opioids could also result in analgesic tolerance. In fact, Sluka and colleagues demonstrate, in rats, that daily administration of low or high frequency TENS leads to the development of analgesic tolerance with a corresponding cross-tolerance to intrathecally administered µ- and δ-opioid agonists, respectively. In clinical practice, TENS is usually applied daily over many weeks. Approximately 30% of patients fail to respond to TENS and, of the patients who respond initially, only a third continue to obtain pain relief after two years. Solomon and colleagues showed that people who had been taking opioids long enough to develop tolerance prior to surgery did not respond to TENS when used postoperatively. Although commonly accepted that TENS reduces its efficacy with repeated application, the development of tolerance to TENS has not been investigated and confirmed in human subjects. We hypothesize that repeated daily treatment with TENS, delivered daily at the same intensity and for the same amount of time (i.e. same dose), will result in a decreased reduction in pain thresholds, an increased temporal summation, and a loss of descending inhibition by the 5th day of treatment.