The long term goal of this project is to elucidate the mechanism of sympathetically maintained pain (SMP). Three hypotheses are proposed regarding development of maintenance of SMP after spinal nerve ligation; 1) sympathetic sprouting in the dorsal root ganglion (DRG) is an important causal factor of SMP, 2) this sympathetic sprouting is induced by increased levels of nerve growth factor (NGF) in the DRG, and 3) susceptibility to SMP depends on amount of NGF production in the DRG.
Six specific aims are formulated to test these hypotheses in the Chung model of neuropathic rat. Sympathetic sprouting in the DRG (Specific Aim 1) will be assayed by double immunofluorescent labeling of sympathetic fibers for tyrosine hydroxylase (TH) and growth associated protein GAP-43. Sympathetic synaptic endings and contacts and possible sites of sympathetic effects on sensory neurons int he DRG of injured nerve (Specific Aim 2) will be quantified by electron microscopic immunostaining and correlated to neuropathic pain behaviors. The NGF levels in the DRG of neuropathic rats (Specific Aim 3) will be tested by an enzyme linked immunosolvent assay (ELISA) method. The effects of nti-NGF on SMP (Specific Aim 4) will be tested by infusing anti-NGF into the DRG of neuropathic rats and then examining pain behaviors and sympathetic sprouting. The changes of NGF levels and sympathetic sprouting in the DRG of Brown Norwary (BN) and Sasco Sprague-Dawley (SD) neuropathic rats, which are less susceptible to SMP, will be determined (Specific Aim 5) and correlated to pain behaviors. The effects of NGF on SMP in BN and Sasco SD neuropathic rats (Specific Aim 6) will be tested by infusing NGF into DRG of neuropathic rats and examining pain behaviors and sympathetic sprouting. Successful completing of th project should advance our understanding of the mechanisms of SMP and suggest treatments of neuropathic pain patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS035057-04
Application #
2883692
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Program Officer
Kitt, Cheryl A
Project Start
1996-05-03
Project End
2001-02-28
Budget Start
1999-03-01
Budget End
2000-02-29
Support Year
4
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Texas Medical Br Galveston
Department
Neurosciences
Type
Schools of Medicine
DUNS #
041367053
City
Galveston
State
TX
Country
United States
Zip Code
77555
Baik, Eunjoo; Chung, Jin Mo; Chung, Kyungsoon (2003) Peripheral norepinephrine exacerbates neuritis-induced hyperalgesia. J Pain 4:212-21
Kim, Chang Hoon; Oh, Youngsuk; Chung, Jin Mo et al. (2002) Changes in three subtypes of tetrodotoxin sensitive sodium channel expression in the axotomized dorsal root ganglion in the rat. Neurosci Lett 323:125-8
Chung, Jin Mo; Chung, Kyungsoon (2002) Importance of hyperexcitability of DRG neurons in neuropathic pain. Pain Pract 2:87-97
Chung, K; Chung, J M (2001) Sympathetic sprouting in the dorsal root ganglion after spinal nerve ligation: evidence of regenerative collateral sprouting. Brain Res 895:204-12
Zhou, J; Chung, K; Chung, J M (2001) Development of purinergic sensitivity in sensory neurons after peripheral nerve injury in the rat. Brain Res 915:161-9
Kim, C H; Oh, Y; Chung, J M et al. (2001) The changes in expression of three subtypes of TTX sensitive sodium channels in sensory neurons after spinal nerve ligation. Brain Res Mol Brain Res 95:153-61
Xie, J; Ho Lee, Y; Wang, C et al. (2001) Differential expression of alpha1-adrenoceptor subtype mRNAs in the dorsal root ganglion after spinal nerve ligation. Brain Res Mol Brain Res 93:164-72
Park, S K; Chung, K; Chung, J M (2000) Effects of purinergic and adrenergic antagonists in a rat model of painful peripheral neuropathy. Pain 87:171-9
Lyu, Y S; Park, S K; Chung, K et al. (2000) Low dose of tetrodotoxin reduces neuropathic pain behaviors in an animal model. Brain Res 871:98-103
Shen, H; Chung, J M; Chung, K (1999) Expression of neurotrophin mRNAs in the dorsal root ganglion after spinal nerve injury. Brain Res Mol Brain Res 64:186-92

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