Afferent neural activity arising from peripheral baroreceptors monitoring cardiovascular function not only produces CNS-mediated reflex adjustments of the circulation, but also activates CNS systems that inhibit pain. The primary goals of this proposal are to identify medullary and spinal cord structures of this cardiovascular pain regulatory network in the rat, establish the efficacy of putative transmitters of primary baroreceptor afferents in producing hypoalgesia or a diminished sensitivity to pain, and determine the range of influence of this network. The regions of the medulla and spinal cord under investigation include the nucleus tractus solitarius (NTS), nucleus raphe magnus (NRM), lateral reticular nucleus (LRN), dorsolateral funiculus (DLF), and ventrolateral funiculus (VLF) based upon their established roles in both cardiovascular and nociceptive function. The importance of these regions in the production of hypoalgesia will be determined through the use of electrolytic and mechanical lesions, and pressure microinjection of pharmacologic agonists and antagonists. Hypoalgesia will be induced by several peripheral cardiovascular stimulus operations including physiological (volume expansion), pharmacological (administration of veratrum alkaloids, enkephalinamide, phenylephrine, or norepinephrine), or electrical activation of cardiopulmonary or sinoaortic baroreceptor afferents. Pain sensitivity will be indexed through behavioral responses in tail-flick, hot-plate, and flinch-jump tests. These experiments will serve to delineate the nature of cardiovascular-pain regulatory interactions and thereby establish how physiological stimuli activate endogenous systems that inhibit pain. These studies will also clarify the mechanisms which mediate a diverse range of phenomena including stress-induced analgesia, the action of peripherally circulating enkephalins in producing analgesia, and the inhibition of cardiac pain.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS022966-03
Application #
3405839
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1985-12-01
Project End
1988-11-30
Budget Start
1987-12-01
Budget End
1988-11-30
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Iowa
Department
Type
Schools of Arts and Sciences
DUNS #
041294109
City
Iowa City
State
IA
Country
United States
Zip Code
52242
Thurston, C L; Randich, A (1995) Responses of on and off cells in the rostral ventral medulla to stimulation of vagal afferents and changes in mean arterial blood pressure in intact and cardiopulmonary deafferented rats. Pain 62:19-38
Thurston, C L; Randich, A (1992) Electrical stimulation of the subdiaphragmatic vagus in rats: inhibition of heat-evoked responses of spinal dorsal horn neurons and central substrates mediating inhibition of the nociceptive tail flick reflex. Pain 51:349-65
Randich, A; Gebhart, G F (1992) Vagal afferent modulation of nociception. Brain Res Brain Res Rev 17:77-99
Thurston, C L; Randich, A (1992) Effects of vagal afferent stimulation on ON and OFF cells in the rostroventral medulla: relationships to nociception and arterial blood pressure. J Neurophysiol 67:180-96
Randich, A; Thurston, C L; Ludwig, P S et al. (1991) Antinociception and cardiovascular responses produced by intravenous morphine: the role of vagal afferents. Brain Res 543:256-70
Aicher, S A; Lewis, S J; Randich, A (1991) Antinociception produced by electrical stimulation of vagal afferents: independence of cervical and subdiaphragmatic branches. Brain Res 542:63-70
Thurston, C L; Randich, A (1991) Quantitative characterization and spinal substrates of antinociception produced by electrical stimulation of the subdiaphragmatic vagus in rats. Pain 44:201-9
Thurston, C L; Randich, A (1990) Acute increases in arterial blood pressure produced by occlusion of the abdominal aorta induces antinociception: peripheral and central substrates. Brain Res 519:12-22
Randich, A; Ren, K; Gebhart, G F (1990) Electrical stimulation of cervical vagal afferents. II. Central relays for behavioral antinociception and arterial blood pressure decreases. J Neurophysiol 64:1115-24
Aicher, S A; Randich, A (1990) Antinociception and cardiovascular responses produced by electrical stimulation in the nucleus tractus solitarius, nucleus reticularis ventralis, and the caudal medulla. Pain 42:103-19

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