• Carstens, Earl (PI)

Project: Research project

Project Details


Analgesia is produced by stimulation of medullary nucleus raphe magnus
(NRM), midbrain periaqueductal gray (PAG), diencephalic periventricular
gray (PVG), medial basal forebrain, lateral hypothalamus (LH), ventrobasal
thalamus (VB), and internal capsule. PAG, PVG and basal forebrain
stimulation powerfully inhibited responses of spinal dorsal horn neurons to
noxious skin heating, and inhibition was blocked by drugs which disrupt the
central action of the neurotransmitter 5-hydroxytryptamine (5-HT,
serotonin), suggesting that these areas constitute a functionally
homogeneous medial serotonergic inhibitory system. Dorsal horn neurons are
also inhibited by stimulation of medial thalamus, LH, contralateral VB,
internal capsule and contralateral somatosensory cortex, and basal
ganglia. The functional relationship of these latter areas to PAG and PVG,
and pathways for inhibition will be studied electrophysiologically.
Descending inhibition of dorsal horn nociceptive neurons may be an
important mechanism underlying analgesia, a better understanding of which
will aid in developing more effective pain therapies. Microelectrodes will
be used to record the responses of single lumbar dorsal horn neurons to
noxious heat stimuli (50 degrees C) applied to glabrous footpad skin in
anesthetized cats. Stimulating electrodes will be stereotaxically
positioned at the target brain sites, and electrical stimulus trains
applied simultaneously with the noxious skin heat stimulus to determine
effects (quantified as the percent reduction in the neuronal heat-evoked
response during brain stimulation in relation to the control response
without brain stimulation). Effects of stimulation at each site (medial
thalamus, LH, VB, cortex, basal ganglia) on neuronal intensity coding for
graded noxious heat stimuli, and ability of 5-HT antagonists (methysergide)
or depletion (with p-chlorophenylalanine) and the opiate antagonist
naloxone to block inhibition, will be compared with similar data on PAG and
PVG/basal forebrain stimulation. The possibility that inhibition from PVG
and other sites is mediated via activation of a proposed PAG-NRM-spinal
inhibitory system will be tested by determining if (a) inhibition is
blocked following PAG or NRM lesions, and (b) neurons in PAG and NRM
(recorded with microelectrodes in anesthetized cats) are activated by
stimulation of PVG and other sites. The possible role of the corticospinal
tract in descending inhibition will be investigated.
Effective start/end date4/1/833/31/87


  • National Institutes of Health


  • Medicine(all)
  • Neuroscience(all)


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