title: A central neuropathic pain model by DSP-4 induced lesion of noradrenergic neurons: preliminary report.
abstract: Neuropathic pain models are classified as central and peripheral pain models. Although various peripheral neuropathic pain models are established, central pain models are based only on spinal cord injury. DSP-4 is a competitive inhibitor of norepinephrine uptake that selectively degenerates the locus coeruleus (LC)-noradrenergic neurons projection to the cerebral cortex and hippocampus. In the present study, we have tested whether lesion of LC-noradrenergic neurons by ip DSP-4 (0, 10, 30, 50 mg/kg, n=7 each) could provide a new central neuropathic pain model in rats using a hot-plate and tail-flick tests. DSP-4 significantly reduced the hot-plate latency and norepinephrine contents especially in the coerulean regions. However, DSP-4 did not change tail-flick latency. There are significant correlations of the latency in the hot-plate test with norepinephrine contents in the cerebral cortex (r=0.432, p=0.022), the hippocampus (r=0.465, p=0.013) and the pons (r=0.400, p=0.035) but not with those in the hypothalamus and the spinal cord. As response to hot-plate and tail-flick implies supra-spinal process and spinal reflex, respectively, central neuropathic pain may be facilitated by DSP-4 depleting LC-noradrenergic neurons although the present data are preliminary.
authors.affiliation: Department of Anesthesiology, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki 036-8562, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kudo
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kushikata
authors.forename: Mihoko
authors.initials: M
authors.lastname: Kudo
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Kudo
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Hirota
mesh_terms: D000818:Animals; D001596:Benzylamines / Q000633:toxicity*; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D008125:Locus Coeruleus / Q000187:drug effects / Q000473:pathology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009498:Neurotoxins / Q000633:toxicity*; D009638:Norepinephrine / Q000378:metabolism*; D010146:Pain / Q000139:chemically induced* / Q000473:pathology*; D010147:Pain Measurement / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D013116:Spinal Cord / Q000473:pathology; D013223:Statistics as Topic
chemical_list: D001596:Benzylamines; D009498:Neurotoxins; C012102:DSP 4; D009638:Norepinephrine