We apply best practices of functional neuroimaging methods (receptor binding PET and multimodal Magnetic Resonance including BOLD fMRI, ASL, diffusion imaging, and structural imaging) to the investigation of pain perception and modulation of pain perception by placebo and acupuncture. We have begun to clarify the neural mechanisms contributing to the unconscious modulation of pain perception in healthy subjects and in patients suffering from chronic pain disorders. By using the novel treatment modality of acupuncture, a system of healing still quite new in this country, we are able to control for confounds due to prior conditioning that are associated with more commonly studied analgesic treatment modalities (pills or topical creams). We have demonstrated that there are multiple mechanisms by which the human brain can modulate pain perception and have proposed a theoretical framework for interpreting the seemingly disparate neuroimaging findings reported in the literature. Importantly, we have chosen to encompass the alternative medical practice of acupuncture as part of our system of study, thus extending these powerful approaches to the integrative medical community.