There is substantial evidence that neurons in the midbrain periaqueductal grey region (PAG) play an important role in the modulation of central pain pathways and partially mediate the analgesic effects of systemic morphine. Descending connections from PAG to the medullary raphe region (particularly nucleus raphe magnus) and ascending projections from PAG to the thalamus (including the ventrobasal complex) may be important pathways that underlie these effects. To define better the anatomic organization and functional circuitry of PAG, a series of experiments will be performed to study the efferent connections, transmitter histochemistry, and electrophysiology of PAG cells. Specific projects will: I. Determine whether individual PAG neurons project to both the ventrobasal complex and raphe magnus. The distribution of PAG neurons projecting to the ventrobasal complex and raphe magnus will be studied with double-label retrograde transport methods using horseradish peroxidase and fluorochromes. Double-label techniques will determine whether the same PAG neurons that have descending connections to raphe magnus also project directly to the thalamus. II. Identify the neuropeptide content of OAG neurons that project to the ventrobasal complex or raphe magnus. Numerous studies provide evidence that specific neuropeptides may be important in PAG-mediated somatosensory effects. Combined retrograde transport-immunocytochemical methods will be used to determine which neuropeptides are associated with PAG neurons that project to the ventrobasal complex or raphe magnus. III. Characterize the afferent inputs to PAG neurons. Antidomically identified PAG neurons projecting to thalamus or raphe magnus will be studied using intracellular electrophysiologic methods in anesthetized, paralyzed cats. The orthodromic responses of such cells to shock stimulation of the amygdala, lateral hypothalamus, medullary reticular formation and internal capsule will be determined. The response of PAG neurons to potentially noxious shock stimulation of peripheral nerves and tooth pulp will also be investigated. IV. Study the anatomy of electrophysiologically characterized PAG neurons. Selected, electrophysiologically defined PAG neurons will be intracellularly stained with horseradish peroxidase. The location, somatodendritic arboriztion, and initial axonal projection of these cells will be reconstructed at the light microscope level using camera lucida techniques. Intracellular staining will make it possible to determine whether PAG neurons that differ electrophysiologically are also distinct in their location, appearance, and efferent projections.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Academic/Teacher Award (ATA) (K07)
Project #
5K07NS000634-05
Application #
3078066
Study Section
Communicative Disorders Review Committee (CDR)
Project Start
1981-07-01
Project End
1986-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
5
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
Mason, P; Strassman, A; Maciewicz, R (1988) Serotonin immunocytochemistry of physiologically characterized raphe magnus neurons. Exp Brain Res 73:1-7
Chung, R Y; Mason, P; Strassman, A et al. (1987) Suppression of the jaw-opening reflex by periaqueductal gray stimulation is decreased by paramedian brainstem lesions. Brain Res 403:172-6
Strassman, A; Mason, P; Eckenstein, F et al. (1987) Choline acetyltransferase immunocytochemistry of Edinger-Westphal and ciliary ganglion afferent neurons in the cat. Brain Res 423:293-304
Chung, R Y; Mason, P; Strassman, A et al. (1987) Edinger-Westphal nucleus: cells that project to spinal cord contain corticotropin-releasing factor. Neurosci Lett 83:13-9
Mason, P; Strassman, A; Maciewicz, R (1986) Intracellular responses of raphe magnus neurons during the jaw-opening reflex evoked by tooth pulp stimulation. Brain Res 379:232-41
Strassman, A; Mason, P; Moskowitz, M et al. (1986) Response of brainstem trigeminal neurons to electrical stimulation of the dura. Brain Res 379:242-50
Mason, P; Strassman, A; Maciewicz, R (1985) Is the jaw-opening reflex a valid model of pain? Brain Res 357:137-46
Mason, P; Strassman, A; Maciewicz, R (1985) Pontomedullary raphe neurons: monosynaptic excitation from midbrain sites that suppress the jaw opening reflex. Brain Res 329:384-9