The present proposal extends our multidisciplinary studies of nonopiate analgesia systems. The long term aim is to better understand the behavioral, neurophysiological, anatomical, and pharmacological bases of pain inhibition produced by focal electrical stimulation of specific brainstem areas (midbrain periaqueductal gray=PAG and lateral reticular formation=LRF; hypothalamus; medullary nucleus raphe magnus=NRM and adjacent reticular formation=MRF). This understanding should lead to more effective and innovative means of clinical pain alleviation. Specific goals are: (A) To utilize behavioral methods in rats (tail-flick reflex latency) to assess the presence or absence of analgesia (stimulation-produced analgesia=SPA) and other behavioral reactions evoked by stimulation in PAG, LRF, hypothalamus, MRF, NRM and other sites. (B) To use electrophysiological single-unit microelectrode recording methods to investigate associated inhibitory (or other) effects on noxious heat-evoked responses of single lumbar spinal cord neurons produced by brain stimulation that either did or did not elicit SPA in the same animals (anesthetized with sodium pentobarbital). (C) To develop a new behavioral methodology enabling a quantitative analysis of brainstem modulation of nociceptive behavior (hindlimb flexion withdrawal reflex) for comparison with spinal reflexes and single spinal neuronal activity elicited by identical noxious thermal hindfoot stimulation. This method derives from our earlier work showing that noxious heating of the anesthetized rat's hindfoot elicits hindlimb flexor EMG activity and withdrawal force which are graded with stimulus temperature and which are suppressed by PAG or LRF stimulation. We will study effects of brain stimulation on hindlimb flexor EMG activity and tension (recorded with a miniature strain gauge implanted in tendon of the biceps femoris muscle) elicited by mild, escapable noxious heat stimuli applied to the ventral hindpaw of awake rats. (D) To investigate the pharmacology of SPA and descending inhibitionof spinal neurons, with particular emphasis on monoaminergic, cholinergic, and peptidergic (cholecystokinin, vasopressin) involvement at spinal or supraspinal sites. (E) To investigate the intraspinal and brainstem trajectories of anatomical pathways mediating SPA and descending inhibition of spinal neurons.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS020037-04
Application #
3400213
Study Section
Communication Sciences and Disorders (CMS)
Project Start
1983-12-01
Project End
1989-11-30
Budget Start
1986-12-01
Budget End
1987-11-30
Support Year
4
Fiscal Year
1987
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
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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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