Research conducted in the last 10 years has increased our knowledge on pain mechanisms substantially. Although many local tissue mediators, including neuropeptides, are known to exert pro-inflammatory effects, comparatively little is known about the actual tissue levels of these inflammatory mediators and their pharmacologic regulation. This article describes two new methods, clinical microdialysis and superfusion of dental pulp, which provide data on the pharmacology of peripheral neuropeptide and inflammatory mediator release. Collectively, these methods provide a biochemically based approach toward determining the mechanisms and management of orofacial pain.