The aim of the present study is to test the hypothesis that large-diameter myelinated muscle afferents contribute to the pathophysiology of myofascial trigger points (MTrPs). The ischemic compression blockage (ICB) of large-diameter myelinated muscle afferents was obtained with a 7-cm-wide tourniquet applied around the upper arm proximal to the brachioradialis muscle in 20 healthy subjects. This study consisted of two randomized sessions with an interval of 1 week in between each session. In one session, pressure pain threshold (PPT) and pressure threshold for eliciting referred pain (PTRP) were measured at an MTrP region in the brachioradialis muscle in one forearm. In another session, PPT was measured at a non-MTrP region in the brachioradialis muscle of the contralateral forearm at the time of pre-compression, 20 min following compression, and 10 min after decompression. The results showed that ICB, which mainly blocks large-diameter myelinated muscle afferents, was associated with an increase in PPT and PTRP (all P < 0.001) at MTrP regions but not at non-MTrP regions. These results suggest that large-diameter muscle afferents may be involved in pain and mechanical hyperalgesia at MTrPs.