The objectives of the proposed experiments are (1) to determine the selectivity for nociceptive input of the spinal inhibition descending from the brain stem, correlating the spinal inhibition with the analgesias produced by focal electrical stimulation and morphine given at selected sites in the brain stem, and (2) to clarify the organization in the brain stem of descending systems of analgesia/inhibition. Rats will be chronically implanted with 26 guage guide cannula(e), through which either a stimulating electrode or injection cannula can be passed. Both the electrodes and injection cannulae will be of identical length to permit stimulation and morphine administration at identical sites in the brain stem. The effect(s) of stimulation and morphine given in the periaqueductal gray, lateral mesencephalic reticular formation, nucleus raphe magnus, and lateral medullary reticular formation on both noxious (radiant heat, electrical C-fiber activation) and non-noxious (brush, electrical A Alpha, Beta-activation) evoked spinal neuronal activity will be quantitatively examined. At all four sites in the brain stem, morphine will be compared with stimulation. In other experiments, stimulation at one site will be compared with stimulation at another site. Significantly, prior to the electrophysiologic evaluation of spinal neurons, the analgetic efficacy of stimulation and morphine will be evaluated in several analgesiometric tests organized at different levels of the CNS to allow correlation of the analgesia produced with the descending inhibitory effects subsequently examined electrophysiologically in the same animals. The study will determine whether there exists a descending system(s) which is selectively analgetic and further our understanding of the brain stem pathways and mechanisms of spinal inhibition.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS019912-03
Application #
3400045
Study Section
Communication Sciences and Disorders (CMS)
Project Start
1983-07-01
Project End
1986-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
3
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Iowa
Department
Type
Schools of Medicine
DUNS #
041294109
City
Iowa City
State
IA
Country
United States
Zip Code
52242
Malet, Mariana; Brumovsky, Pablo R (2015) VGLUTs and Glutamate Synthesis-Focus on DRG Neurons and Pain. Biomolecules 5:3416-37
Feng, Bin; La, Jun-Ho; Schwartz, Erica S et al. (2012) Long-term sensitization of mechanosensitive and -insensitive afferents in mice with persistent colorectal hypersensitivity. Am J Physiol Gastrointest Liver Physiol 302:G676-83
La, J H; Schwartz, E S; Gebhart, G F (2011) Differences in the expression of transient receptor potential channel V1, transient receptor potential channel A1 and mechanosensitive two pore-domain K+ channels between the lumbar splanchnic and pelvic nerve innervations of mouse urinary bladder and col Neuroscience 186:179-87
Brumovsky, Pablo R; Seroogy, Kim B; Lundgren, Kerstin H et al. (2011) Some lumbar sympathetic neurons develop a glutamatergic phenotype after peripheral axotomy with a note on VGLUT?-positive perineuronal baskets. Exp Neurol 230:258-72
Brumovsky, Pablo R; Robinson, David R; La, Jun-Ho et al. (2011) Expression of vesicular glutamate transporters type 1 and 2 in sensory and autonomic neurons innervating the mouse colorectum. J Comp Neurol 519:3346-66
Tanaka, T; Shinoda, M; Feng, B et al. (2011) Modulation of visceral hypersensitivity by glial cell line-derived neurotrophic factor family receptor α-3 in colorectal afferents. Am J Physiol Gastrointest Liver Physiol 300:G418-24
Schwartz, Erica S; Christianson, Julie A; Chen, Xiaowei et al. (2011) Synergistic role of TRPV1 and TRPA1 in pancreatic pain and inflammation. Gastroenterology 140:1283-1291.e1-2
Feng, Bin; Gebhart, G F (2011) Characterization of silent afferents in the pelvic and splanchnic innervations of the mouse colorectum. Am J Physiol Gastrointest Liver Physiol 300:G170-80
La, Jun-Ho; Gebhart, G F (2011) Colitis decreases mechanosensitive K2P channel expression and function in mouse colon sensory neurons. Am J Physiol Gastrointest Liver Physiol 301:G165-74
Feng, Bin; Brumovsky, Pablo R; Gebhart, Gerald F (2010) Differential roles of stretch-sensitive pelvic nerve afferents innervating mouse distal colon and rectum. Am J Physiol Gastrointest Liver Physiol 298:G402-9

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