We will continue to investigate descending inhibitory control of spinal nociceptive transmission. Our long-term objective is to clarify the organization and selectivity of centrifugal inhibitory influences on spinal dorsal horn neurons by quantitatively evaluating the effects of drugs and focal electrical stimulation applied in selected sites in the brain stem on both noxious and non-noxious spinal afferent input, correlating the spinal inhibition with the analgesia produced by the same treatments.
The specific aims i nclude: quantitative characterization and comparison of the inhibition of spinal dorsal horn neurons produced by opioids and/or focal electrical stimulation given in the brain stem; quantitative characterization of centrifugal inhibitory influences on visceral pain and comparison with inhibition of somatocutaneous pain; characterization of a pseudoaffective pressor reflex produced by noxious visceral stimulation and its centrifugal modulation; and investigation of the organization and interaction in the brain stem of descending inhibitory influences on spinal nociceptive transmission.
These aims will be achieved by extracellular single unit recording in the lumbosacral spinal cord of the rat, intracerebral focal electrical stimulation and drug microinjections at the same sites in the brain stem, and intrathecal administration of drugs. These experiments will initiate important investigations into visceral pain, characterizing the stimulus and its relationship to a pseduoaffective pressor reflex, neurons responding in the spinal dorsal horn, somatovisceral convergence, and descending modulation. In all experiments, use of noxious and non-noxious stimuli will be employed to address whether a descending system selectively affects noxious afferent input. Descending inhibitory influences of drugs and stimulation will also be compared and contrasted with their analgetic effects behaviorally. Results of these experiments will provide new information about centrifugal modulation of somatic and visceral pain and clarify the organization in the brain stem of descending systems of inhibition/analgesia.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
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Sensory Disorders and Language Study Section (CMS)
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University of Iowa
Schools of Medicine
Iowa City
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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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