The proposed experiments will examine both the peripheral and central neural mechanisms involved in the mediation and modulation of sensory transmission in the trigeminovascular system, a clinically relevant model of visceral nociception. I. Determine the responses of brainstem trigeminal neurons to chemical and mechanical stimulation of cranial blood vessels. Neurons in the spinal trigeminal nucleus that are activated by stimulation of cranial blood vessels and also receive a nociceptive cutaneous input from the periorbital region may be involved in mediating vascular head pain. The propose experiments will father examine the vascular responses of trigeminal neurons by recording their activity extracellularly during mechanical and chemical stimulation of the lingual and middle meningeal arteries The arteries will be stimulated mechanically by intra-arterial balloon inflation and chemically by perfusion of surgically isolated arterial segments with algesic substances. II. Determine the degree of convergence from multiple visceral and somatic afferent pathways onto individual trigeminovascular neurons. In addition to their potential role in vascular head pain, nociceptive trigeminal neurons with convergent viscerosomatic inputs may also be involved in mediating other types of cranial and facial pain by relaying afferent input from additional visceral and deep structures. Trigeminal neurons that receive a vascular input will be tested for responses to stimulation of additional visceral and deep structures of the head and face, including tooth pulp, temporomandibular joint, temporalis muscle, and masseter muscle. III. Examine the modulation of visceral and somatic responses in trigeminovascular neurons during central and peripheral stimulation. The responses of nociceptive trigeminal neurons with convergent viscerosomatic inputs twill be tested for suppression or enhancement of their responses by conditioning stimulation of nucleus raphe magnus and periaqueductal gray, as well as by conditioning stimulation at peripheral sites both within and outside the neuron's receptive field. IV. Determine the location and morphology of brainstem trigeminovascular neurons. The location, somadendritic morphology, and initial axonal trajectory of neurons that peroxidase, and compared to neurons that receive only a cutaneous input.
