) Chronic pain due to disease or injury of the peripheral or central nervous system (chronic neuropathic pain or CNP) continues to present a serious obstacle for the psychological and social adjustment of persons with neurologic disabilities. The rehabilitation of these patients would improve if more was known about the cause of CNP and the frequent failure of CNP to respond to treatment. This Program Project is designed to advance the understanding of several factors that influence the development of CNP and its resistance to treatment in patients with spinal cord injury (SCI) and brachial plexus injury (BPI). The overall hypothesis is that CNP, and its resistance to treatment, is caused or maintained by a maladaptive reorganization of forebrain responses to somatic stimulation adjacent to the denervated region. Patients and normal control subjects will be recruited by the Clinical Core (Dr. Leonard) where clinical, psychological, and psychophysical evaluations and pain treatment protocols will be conducted. In project l (Dr. Minoshima), regional cerebral blood flow (rCBF) responses, indicative of synaptic activity, will be analyzed in patients and normal subjects receiving noxious and innocuous infra-red laser stimulation to each side of the neck (above the affective site in patients). Subtraction techniques across and within subjects will be used to identify pain and CNP-specific responses and response changes. The effect on these responses of treatment with a tricyclic antidepressant (TCA) will be determined. In project 2 (Dr. Beydoun), infra-red laser evoked potentials (LEPs) will be recorded from patients and normal subjects receiving laser stimulation of the hand, neck, and sites immediately adjacent to the denervation region. Principle components and dipole localization analyses will be used for 3 dimensional spatial and temporal localization of LEP components. Pain and CNP-specific LEP responses and response changes will be determined by subtraction methods and longitudinal comparisons of CNP developments within patients. The effect of TCS therapy on LEP components and laser psychophysical measures will be determined. In project 3 (Dr. Morrow), the development off specific patterns of the forebrain rCBF response to CNP and CA analgesia will be identified in the rat, using high resolution quantitative autoradiography and the chronic sciatic nerve ligature model of CNP. Behavioral measures of chronic and evoked nocifensive responses will be correlated with changes in the pattern of stimulus-evoked responses to noxious and innocuous somatic stimuli.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Program Projects (P01)
Project #
5P01HD033986-05
Application #
6181723
Study Section
Special Emphasis Panel (SRC (PM))
Program Officer
Quatrano, Louis A
Project Start
1996-09-30
Project End
2002-07-31
Budget Start
2000-08-01
Budget End
2002-07-31
Support Year
5
Fiscal Year
2000
Total Cost
$506,259
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Neurology
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Casey, Kenneth L; Geisser, Michael; Lorenz, Jürgen et al. (2012) Psychophysical and cerebral responses to heat stimulation in patients with central pain, painless central sensory loss, and in healthy persons. Pain 153:331-41
Paulson, Pamela E; Gorman, A L; Yezierski, Robert P et al. (2005) Differences in forebrain activation in two strains of rat at rest and after spinal cord injury. Exp Neurol 196:413-21
Hong, Shuangsong; Morrow, Thomas J; Paulson, Pamela E et al. (2004) Early painful diabetic neuropathy is associated with differential changes in tetrodotoxin-sensitive and -resistant sodium channels in dorsal root ganglion neurons in the rat. J Biol Chem 279:29341-50
Casey, Kenneth L; Lorenz, Jurgen; Minoshima, Satoshi (2003) Insights into the pathophysiology of neuropathic pain through functional brain imaging. Exp Neurol 184 Suppl 1:S80-8
Lorenz, J; Minoshima, S; Casey, K L (2003) Keeping pain out of mind: the role of the dorsolateral prefrontal cortex in pain modulation. Brain 126:1079-91
Lorenz, Jurgen; Cross, Donna J; Minoshima, Satoshi et al. (2002) A unique representation of heat allodynia in the human brain. Neuron 35:383-93
Paulson, Pamela E; Casey, Kenneth L; Morrow, Thomas J (2002) Long-term changes in behavior and regional cerebral blood flow associated with painful peripheral mononeuropathy in the rat. Pain 95:31-40
Casey, K L; Morrow, T J; Lorenz, J et al. (2001) Temporal and spatial dynamics of human forebrain activity during heat pain: analysis by positron emission tomography. J Neurophysiol 85:951-9
Paulson, P E; Morrow, T J; Casey, K L (2000) Bilateral behavioral and regional cerebral blood flow changes during painful peripheral mononeuropathy in the rat. Pain 84:233-45
Casey, K L; Svensson, P; Morrow, T J et al. (2000) Selective opiate modulation of nociceptive processing in the human brain. J Neurophysiol 84:525-33

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