The long-term objectives of our research program are to clarify the central mechanisms underlying acute and chronic craniofacial pain and its control. Our recent NIH-supported research has resulted in major new insights into the neuroplasticity of the trigeminal (V) brainstem complex, and into brainstem mechanisms underlying deep (e.g. muscle; and temporomandibular joint, TMJ) as well as cutaneous (facial) pain. These latter studies, carried out in subnucleus caudalis since it has been particularly implicated in orofacial pain mechanisms, have suggested mechanisms that may be involved in signaling pain and in its spread and referral and that may be manifested in pathophysiological situations such as temporomandibular/myofascial pain dysfunction and inflammation. To clarify these mechanisms further, we will first address hypotheses that A: Caudalis neurons receiving deep as well as cutaneous nociceptive afferent inputs project directly to the posterior thalamus and/or parabrachial area, PBA; B: Application of an inflammatory irritant to masticatory muscle( masseter and tongue muscles) or temporomandibular (TM) region enhances the peripherally evoked responses to cutaneous or deep stimuli of caudalis nociceptive neurons; block of C-fiber afferents markedly diminishes this enhancement; and C: Descending modulatory influences from the periaqueductal gray (PAG) and rostroventral medulla (RVM) can depress the peripherally evoked responses to deep as well as cutaneous stimuli of caudalis nociceptive neurons; local anesthesia or lesioning of RVM can diminish the depressive effects of PAG stimulation. Electrophysiological recordings will be made from functionally identified brainstem nociceptive and nonnociceptive neurons in subnucleus caudalis of rats to determine if neurons receiving deep nociceptive afferent inputs project to regions implicated in more central processing of pain and if these neurons' activity can be modulated by TM and muscle afferents excited by irritant substances and by central modulatory influences implicated in the control of pain. Since neural alterations associated with injury and inflammation may be involved in several craniofacial pain conditions including temporomandibular/ myofascial pain dysfunction, the information gained from this research will provide a better understanding of acute and chronic craniofacial pains and their control.