Endomorphin-2 and tetrapeptide derivatives thereof are described. Pharmaceutical or cosmetic compositions containing endomorphin-2 or a tetrapeptide derivative thereof are therapeutically effective to treat, improve or prevent pain in human subjects, such as pain associated with a disorder, disease, condition, symptom, or syndrome of the nervous system, musculoskeletal system, vascular system, immune system, tumors or cancers, including, but not limited to, pain associated with arthritis, headache, muscles or joints upon topical or systemic administration.
