The proposed experiments focus on structures in the brain stem which play important roles in antinociception, on their organization and interrelationship(s) in the brain stem, and on the neurotransmitters involved. The overall objective of the proposed experiments is to clarify the interactions in the brain stem of structures contributing to opioid- and stimulation-produced antinociception and the neurotransmitters in the brain and spinal cord which mediate both opioid- and stimulation-produced antinociception.
The specific aims i nclude: (1) quantitative evaluation and characterization of antinociception produced by morphine and focal electrical stimulation given at identical sites in brain. The brain areas in focus include the lateral hypothalamus, midbrain periaqueductal gray and adjacent reticular formation, the norepinephrine-containing pontine cell groups (A7/parabrachial area, A6 and A5 cell groups), the rostroventral medulla and the medullary lateral reticular nucleus/A1 area. (2) Evaluation of the contributions of areas in the brain stem interposed between the hypothalamus or midbrain and the spinal cord in the antinociception produced by drugs or electrical stimulation given in the hypothalamus or midbrain. And (3) evaluation of neurotransmitters at brain stem relays between the hypothalamus or midbrain and the spinal cord which mediate the descending antinociception produced by drugs or stimulation given in these rostral structures. A variety of approaches will be employed to generate converging pharmacologic, behavioral, neurochemical and electrophysiologic evidence relative to the working hypothesis that functionally important relays between rostral structures in the brain and the spinal cord play important roles in descending antinociceptive mechanisms. These experiments will clarify the organization in the brain stem of structures important to antinociception and the neurotransmitters by which these effects are mediated. Quantitative investigation of the areas in brain selected and elucidation of the transmitters involved will lead to better understanding of the centrifugal modulation of pain.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
2R01DA002879-12
Application #
3207602
Study Section
(SRCD)
Project Start
1981-09-30
Project End
1992-12-31
Budget Start
1988-01-01
Budget End
1988-12-31
Support Year
12
Fiscal Year
1988
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
Hemovich, Vanessa; Crano, William D (2009) Family structure and adolescent drug use: an exploration of single-parent families. Subst Use Misuse 44:2099-113
Buhler, A V; Proudfit, H K; Gebhart, G F (2008) Neurotensin-produced antinociception in the rostral ventromedial medulla is partially mediated by spinal cord norepinephrine. Pain 135:280-90
Tillu, D V; Gebhart, G F; Sluka, K A (2008) Descending facilitatory pathways from the RVM initiate and maintain bilateral hyperalgesia after muscle insult. Pain 136:331-9
Morgan, James R; Gebhart, G F (2008) Characterization of a model of chronic orofacial hyperalgesia in the rat: contribution of NA(V) 1.8. J Pain 9:522-31
Locher-Claus, Maria T; Erickson, Ty E; Law, Alan S et al. (2005) Effects of pre-emptive morphine, ibuprofen or local anesthetic on fos expression in the spinal trigeminal nucleus following tooth pulp exposure in the rat. J Endod 31:578-83
Gebhart, G F (2004) Descending modulation of pain. Neurosci Biobehav Rev 27:729-37
Buhler, A V; Proudfit, H K; Gebhart, G F (2004) Separate populations of neurons in the rostral ventromedial medulla project to the spinal cord and to the dorsolateral pons in the rat. Brain Res 1016:12-9
Friedrich, Ann E; Gebhart, G F (2003) Modulation of visceral hyperalgesia by morphine and cholecystokinin from the rat rostroventral medial medulla. Pain 104:93-101
Hartwig, Andrew C; Mathias, Sarah I; Law, Alan S et al. (2003) Characterization and opioid modulation of inflammatory temporomandibular joint pain in the rat. J Oral Maxillofac Surg 61:1302-9
Zhuo, M; Sengupta, J N; Gebhart, G F (2002) Biphasic modulation of spinal visceral nociceptive transmission from the rostroventral medial medulla in the rat. J Neurophysiol 87:2225-36

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