Musculoskeletal pain affects a significant proportion of the general population. The myofascial trigger point is recognized as a key factor in the pathophysiology of musculoskeletal pain. Ultrasound is commonly employed in the treatment and management of soft tissue pain and, in this study, we set out to investigate the segmental antinociceptive effect of ultrasound. Subjects (n=50) with identifiable myofascial trigger points in the supraspinatus, infraspinatus and gluteus medius muscles were selected from an outpatient rehabilitation clinic and randomly assigned to test or control groups. Test subjects received a therapeutic dose of ultrasound to the right supraspinatus trigger point while control groups received a sham (null) exposure. Baseline pain pressure threshold (PPT) readings were recorded at the ipsilateral infraspinatus and gluteus medius trigger-point sites prior to ultrasound exposure. The infraspinatus point was chosen due to its segmental neurologic link with the supraspinatus point; the gluteus medius acted as a segmental control point. Following the ultrasound intervention, PPT readings were recorded at 1, 3, 5, 10 and 15 min intervals at both infraspinatus and gluteus medius trigger points; the difference between infraspinatus and gluteus medius PPT values, PPT seg, represents the segmental influence on the PPT. The ultrasound test group demonstrated statistically significant increases in PPT seg (decreased infraspinatus sensitivity) at 1, 3 and 5 min, when compared with PPT seg in the sham ultrasound group. These results establish that low-dose ultrasound evokes short-term segmental antinociceptive effects on trigger points which may have applications in the management of musculoskeletal pain.