Ten patients with myofascial trigger point pain were entered into a double-blind cross-over study of the reversibility of myofascial trigger point injection (TPI) effects with naloxone versus placebo in order to test the hypothesis that the benefits of TPI are mediated, at least in part, through activation of an endogenous opioid system. Injection of trigger points with 0.25% bupivacaine decreased pain in all subjects and increased range of motion in subjects who, on initial assessment, demonstrated limitations of movement of the affected part(s). Allodynia and palpable bands preceding TPI when present also showed reduction after TPI. All improvements afforded by TPI were significantly reversed with intravenous naloxone (10 mg) compared to intravenous placebo. These results demonstrate a naloxone-reversible mechanism in TPI therapy. This suggests an endogenous opioid system as a mediator for the decreased pain and improved physical findings following injection of myofascial trigger points with local anesthetic.