Afferent neural activity arising from peripheral mechanoreceptors monitoring cardiopulmonary function not only produces well-characterized CNS-mediated reflex adjustments of the circulation, but also activates CNS systems that modulate noxious somatosensory input. The present proposal is based upon the hypothesis that peripheral and central substrates of baroreceptor reflex control of the circulation are physiologically linked to systems involved in the centrifugal modulation of pain. Thus, the primary objective of this proposal is to parametrically evaluate the modulation of spontaneous and noxious-evoked activity of spinal dorsal horn neurons by manipulations which increase afferent activity of the vagal nerve trunk in the rat. This will be accomplished by extracellular recording of antidromically- identified class 2 (""""""""wide dynamic range"""""""") and class 3 (""""""""nociceptive specific"""""""") neurons of the lumbar spinal dorsal horn activated by either tibial nerve stimulation (A-fiber and A- and C-fiber intensities) or noxious heat stimulation applied to the plantar surface of the hindlimb footpad. Activation of vagal afferents will be effected by two manipulations established as antinociceptive in the rat: electrical stimulation of the vagal trunk or intravenous administration of (D-ala2)- methionine enkephalinamide.
The specific aims of the present proposal are: (1) to provide converging electrophysiological support for existing behavioral data on cardiopulmonary modulation of somatosensory input in the rat; (2) to evaluate the organization of medullary substrates mediating inhibition of spinal nociceptive transmission produced by activation of vagal afferents; and (3) assess potential interactions between known medullary substrates of descending spinal inhibition and those activated by vagal afferents.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS024958-03
Application #
3410007
Study Section
Neurology B Subcommittee 2 (NEUB)
Project Start
1988-07-01
Project End
1990-11-30
Budget Start
1990-07-01
Budget End
1990-11-30
Support Year
3
Fiscal Year
1990
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
Ren, K; Zhuo, M; Randich, A et al. (1993) Vagal afferent stimulation-produced effects on nociception in capsaicin-treated rats. J Neurophysiol 69:1530-40
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
Meller, S T; Lewis, S J; Brody, M J et al. (1991) The peripheral nociceptive actions of intravenously administered 5-HT in the rat requires dual activation of both 5-HT2 and 5-HT3 receptor subtypes. Brain Res 561:61-8
Meller, S T; Lewis, S J; Ness, T J et al. (1991) Neonatal capsaicin treatment abolishes the nociceptive responses to intravenous 5-HT in the rat. Brain Res 542:212-8
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
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
Gebhart, G F; Ness, T J (1991) Central mechanisms of visceral pain. Can J Physiol Pharmacol 69:627-34
Lewis, S J; Meller, S T; Brody, M J et al. (1991) Reduced nociceptive effects of intravenous serotonin (5-HT) in the spontaneously hypertensive rat. Clin Exp Hypertens A 13:849-57
Ren, K; Randich, A; Gebhart, G F (1991) Spinal serotonergic and kappa opioid receptors mediate facilitation of the tail flick reflex produced by vagal afferent stimulation. Pain 45:321-9

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