Chronic pain is a ubiquitous, debilitating and costly affliction of both children and adults. Important aspects of pain-related behavior are mediated by supraspinal mechanisms. The rostral ventromedial medulla (RVM) has both anti- and pro-nociceptive modulatory capabilities, each referable to a distinct, physiologically identified cell class. """"""""Off-cells"""""""" are proposed to inhibit, and """"""""on-cells"""""""" to facilitate, nociceptive processing. The remaining RVM neurons, """"""""neutral cells"""""""", do not alter their activity in relationship to nocifensive behavior, and their role in pain modulation is currently unclear. The proposed research will employ complementary electrophysiological and anatomical approaches (single cell recording and iontophoresis, juxtacellular labeling, and immunohistochemistry) to characterize the distribution of purinergic receptors on the three cell classes. With this information, I will directly and selectively manipulate the activity of each class in order to demonstrate a specific role in nociceptive modulation. My doctoral and post-doctoral research training has centered on the functional anatomy of brainstem catecholaminergic neurons and the neurochemistry of the basal forebrain and striatum. My clinical interest as an academic pediatric neurosurgeon is in functional nervous system diseases such as spasticity, medically refractory epilepsy and movement disorders. My goal is to develop scientific and clinical expertise in central nervous system electro physiology, enabling me to launch an independent and competitively funded laboratory and also to develop a clinical program of neuromodulatory treatment (deep brain stimulation) for movement disorders in children. Oregon Health & Sciences University is an ideal location to pursue these goals. The University is recognized as centers for excellence in neuroscience research and functional neurosurgery. My mentor, Dr. Mary Heinricher, is a well-established and highly productive basic researcher, and my institution has committed to my developing a formal program in functional pediatric neurological surgery, which will complement my basic investigational activities.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08NS044255-05
Application #
7111611
Study Section
NST-2 Subcommittee (NST)
Program Officer
Porter, Linda L
Project Start
2002-09-10
Project End
2008-08-31
Budget Start
2006-09-01
Budget End
2008-08-31
Support Year
5
Fiscal Year
2006
Total Cost
$173,907
Indirect Cost
Name
Oregon Health and Science University
Department
Neurosurgery
Type
Schools of Medicine
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239
Maire, J J; Close, L N; Heinricher, M M et al. (2016) Distinct pathways for norepinephrine- and opioid-triggered antinociception from the amygdala. Eur J Pain 20:206-14
Close, L N; Cetas, J S; Heinricher, M M et al. (2009) Purinergic receptor immunoreactivity in the rostral ventromedial medulla. Neuroscience 158:915-21
Ortiz, J P; Close, L N; Heinricher, M M et al. (2008) Alpha(2)-noradrenergic antagonist administration into the central nucleus of the amygdala blocks stress-induced hypoalgesia in awake behaving rats. Neuroscience 157:223-8
Ortiz, J P; Heinricher, M M; Selden, N R (2007) Noradrenergic agonist administration into the central nucleus of the amygdala increases the tail-flick latency in lightly anesthetized rats. Neuroscience 148:737-43
Selden, N R; Carlson, J D; Cetas, J et al. (2007) Purinergic actions on neurons that modulate nociception in the rostral ventromedial medulla. Neuroscience 146:1808-16
Carlson, Jonathan Dennis; Selden, Nathan Richard; Heinricher, Mary Magdalen (2005) Nocifensive reflex-related on- and off-cells in the pedunculopontine tegmental nucleus, cuneiform nucleus, and lateral dorsal tegmental nucleus. Brain Res 1063:187-94