Transcutaneous electrical nerve stimulation (TENS) reduces pain through central mechanisms involving spinal cord and brainstem sites. Since TENS acts through central mechanisms, we hypothesized that TENS will reduce chronic bilateral hyperalgesia produced by unilateral inflammation when applied either ipsilateral or contralateral to the site of muscle inflammation. Sprague-Dawley rats were injected with carrageenan in the left gastrocnemius muscle belly. Mechanical withdrawal threshold was tested bilaterally before and 2 weeks after carrageenan injection. After testing withdrawal thresholds at 2 weeks, rats received TENS treatment either ipsilateral or contralateral to the site of inflammation. In each of these groups, rats were randomized to control (no TENS), low frequency (4 Hz), or high frequency (100 Hz) TENS treatment. TENS was applied for 20 min at sensory intensity under light halothane anesthesia. Mechanical withdrawal thresholds were re-assessed after TENS or 'no TENS' treatment. Unilateral injection of carrageenan to the gastrocnemius muscle significantly reduced the mechanical withdrawal threshold (mechanical hyperalgesia) bilaterally 2 weeks later. Either low or high frequency TENS applied to the gastrocnemius muscle ipsilateral to the site of inflammation significantly reversed mechanical hyperalgesia, both ipsilateral and contralateral to the site of inflammation. Low or high frequency TENS applied to the gastrocnemius muscle contralateral to the site of inflammation also significantly reduced mechanical hyperalgesia, both ipsilateral and contralateral to the site of inflammation. Since ipsilateral or contralateral TENS treatments were effective in reducing chronic bilateral hyperalgesia in this animal model, we suggest that TENS act through modulating descending influences from supraspinal sites such as rostral ventromedial medulla (RVM).