We are studying mechanisms that underlie the development and maintenance of persistent pain and hyperalgesia. We employ a wide range of techniques including behavioral pharmacology, focal brain microinjection and stimulation, electrophysiology, immunocytochemistry, in situ hybridization histochemistry, RNA and protein analysis using Western and Northern blots, and RT-PCR. This multidisciplinary approach allows as to address the mechanisms of persistent pain at both systemic and molecular levels. Ongoing projects include: 1. CNS Modulation of Persistent Pain and Spinal Plasticity: This project studies how descending brainstem inputs modulate the molecular, biochemical and physiological events leading to the prolonged functional changes in the spinal cord associated with persistent pain and hyperalgesia. 2. Mechanisms of Persistent Temporomandibular (TM) Pain: Disorders of the TM joint often result in persistent pain and therefore are a major health problem. The underlying etiology and pathology associated with these disorders remains unclear. This study is to develop an animal model in which behavioral, physiological, pharmacological and molecular events associated with deep tissue injury and inflammation of the orofacial region can be compared with events following inflammation of cutaneous tissues. 4. Excitatory amino acid receptors and persistent pain: It has been documented recently that glutamate receptors are involved in initiation and maintenance of injury-induced central sensitization, a state of central hyperexcitability, and persistent pain. We are addressing the molecular mechanisms involved in central sensitization.