The objective of this research plan is to begin to evaluate the effects of descending supraspinal modulation on spinal dorsal horn (Rexed laminae IV-VI) neurons. This proposal is unique in that it will involve extracellular recordings from single spinal neurons in intact, awake cats. This will permit an evaluationof the systems as they normally function without confounding influences of anesthesia decerebration or spinal cord transection. Descending inhibitory effects on dorsal horn neurons have been demonstrated, including the assumed analgesic-producing effect of descending inhibition of wide dynamic range (WDR) neurons. This assumed mechanism of analgesia is open to question, however, because of the unknown physiologic role of WDR neurons, as well as the ability of descending inhibition to alter non-nociceptive activity as well. Several lines of evidence would suggest that in the intact animal, descending inhibition may block the ability of dorsal horn neurons to respond with a wide dynamic range profile. In spite of the lack of a clear appreciation of the physiologic role of wide dynamic range neurons. They have been the center of many studies which have evaluated the ability of either physiological or pharmacological manipulations to both alter dorsal horn neuronal activity as well as produce behavioral analgesia. Because of their potentially important role in our understanding of the neurophysiology of analygesia. it is essential that we have a clear appreciation of factors that regulate wide dynamic range neuron response properties in the intact animal. As such, this proposal has, as its specific aims, the following: 1) to determine if tonically active descending inhibition blocks the ability of spinal dorsal horn lumbar neurons to respond with a wid dynamic range profile in the physiologically intace, awake, drug free, behaviorally naive cat. 2) to determine if descending inhibition from the nucleus raphe magnus is involved in this modulation of WDR profiles. 3) to determine if descending inhibition from the nucleus raphe magnus also contributes to the depression of spontaneous activity of dorsal horn neurons in intact animals. 4) to evaluate the effect of serotonin blockage on dorsal horn neurons in the intact animal.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS023033-03
Application #
3406012
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1986-07-01
Project End
1989-12-31
Budget Start
1988-07-01
Budget End
1989-12-31
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Yale University
Department
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520