Pain inhibition is produced by stimulation of the midbrain periaqueductal gray (PAG) and lateral reticular formation (LRF), diencephalic periventricular gray (PVG), medial basal forebrain (MBF) and lateral hypothalamus (LH). Inhibition of nocisponsive dorsal horn neurons produced by stimulating PAG, PVG, LH, and MFB (but not LRF) is reduced by systemically-administered serotonin (5-HT) depletors/blockers, indicating involvement of 5-HT neurotransmission in these pain-suppressive effects. Inhibition produced by PAG, LRF, PVG, and LH stimulation is not blocked by the specific opiate antagonist naloxone, implying that non-opiate pathways underlie these effects. This project will investigate behavioral, neurochemical, neuroanatomical, and neurophysiological aspects of analgesia producted by focal electrical stimulation of these 5 brain sites. Some of the specific goals subsumed under this project include: (1) To thoroughly investigate the behavioral effects of stimulation of these brain areas. This includes determining the (a) specificity of stimulation-induced inhibition, (b) types of pain stimuli suppressed (c) effects of stimulation on the threshold and slope of behavioral stimulus-response functions. (2) To precisely describe the neurocircuitry involved by (a) examining the afferent and efferent projections of these brain sites (b) examining the potential involvement of the spinal cord dorsolateral funiculus, medullary n. raphe magnus and medullary n. reticularis paragigantocellularis in analgesia elicited from various brain sites. (3) To elucidate the role of supraspinal and spinal 5-HT and norepinephrine in analgesia elicited from various brain sites. (4) To be able to suggest new and practical treatment procedures for difficult or intractable pain syndromes in man.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS020037-03
Application #
3400218
Study Section
Communication Sciences and Disorders (CMS)
Project Start
1983-12-01
Project End
1986-11-30
Budget Start
1985-12-01
Budget End
1986-11-30
Support Year
3
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of California Davis
Department
Type
Earth Sciences/Resources
DUNS #
094878337
City
Davis
State
CA
Country
United States
Zip Code
95618
Thurston, C L; Campbell, I G; Culhane, E S et al. (1992) Characterization of intrathecal vasopressin-induced antinociception, scratching behavior, and motor suppression. Peptides 13:17-25
Carstens, E; Campell, I G (1992) Responses of motor units during the hind limb flexion withdrawal reflex evoked by noxious skin heating: phasic and prolonged suppression by midbrain stimulation and comparison with simultaneously recorded dorsal horn units. Pain 48:215-26
Douglass, D K; Carstens, E; Watkins, L R (1992) Spatial summation in human thermal pain perception: comparison within and between dermatomes. Pain 50:197-202
Carstens, E; Leah, J; Lechner, J et al. (1990) Demonstration of extensive brainstem projections to medial and lateral thalamus and hypothalamus in the rat. Neuroscience 35:609-26
Carstens, E; Culhane, E S; Banisadr, R (1990) Partial involvement of monoamines and opiates in the inhibition of rat spinal nociceptive neurons evoked by stimulation in midbrain periaqueductal gray or lateral reticular formation. Brain Res 522:7-13
Watkins, L R; Thurston, C L; Fleshner, M (1990) Phenylephrine-induced antinociception: investigations of potential neural and endocrine bases. Brain Res 528:273-84
Carstens, E; Hartung, M; Stelzer, B et al. (1990) Suppression of a hind limb flexion withdrawal reflex by microinjection of glutamate or morphine into the periaqueductal gray in the rat. Pain 43:105-12
Guinan, M J; Rothfeld, J M; Pretel, S et al. (1989) Electrical stimulation of the rat ventral midbrain elicits antinociception via the dorsolateral funiculus. Brain Res 485:333-48
Carstens, E; Campbell, I G (1988) Parametric and pharmacological studies of midbrain suppression of the hind limb flexion withdrawal reflex in the rat. Pain 33:201-13
Carstens, E (1988) Inhibition of rat spinothalamic tract neuronal responses to noxious skin heating by stimulation in midbrain periaqueductal gray or lateral reticular formation. Pain 33:215-24

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