ABSTRACTSubstance P is thought to be the principle neurotransmitter of nociceptive impulses in type C sensory neurons. Prolonged repeated applications of capsaicin cream depletes the sensory C-fibers of substance P. In an open-labeled prospective pilot study, 23 patients with chronic neck pain (greater than 3 mo) completed the study. Patients applied topical capsaicin (0.025%) cream four times a day to painful areas in the neck and shoulder girdle for a 5-wk treatment period. One patient dropped out because of intolerable burning. Statistically significant improvement was obtained in two primary outcome variables, the visual analog pain scale (P= 0.00013) and the pain relief scale (P= 0.002). Paired f tests failed to show a significant improvement in the McGill Pain Questionnaire. This study demonstrated that topically applied capsaicin cream may decrease subjective neck pain. A double-blind, placebo-controlled trial is needed to confirm this treatment effect.