• Carstens, Earl (PI)

Project: Research project

Project Details


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.
Effective start/end date12/1/8311/30/90


  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health


  • Medicine(all)
  • Neuroscience(all)


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