title: Antinociceptive effects of neurotropin in a rat model of central neuropathic pain: DSP-4 induced noradrenergic lesion.
abstract: Neurotropin is a nonprotein extract isolated from inflamed skin of rabbits inoculated with vaccinia virus, and used for treatment of neuropathic pain. In the present study, we have determined whether neurotropin could exert antinociceptive action using the central neuropathic pain model that we recently established. Rats were randomly allocated to 3 groups: Sham group (n=20), DSP-4 [N-(-2-chloroethyl)-N-ethyl-2-bromobenzylamine] group (50mg/kg ip, n=18), and DSP-4+5,7-DHT [5,7-dihydroxytryptamine] group (ip DSP-4 50mg/kg+icv 5,7-DHT 200μg, n=18). In Sham, DSP-4 and DSP-4+5,7-DHT groups, the effects of ip neurotropin (100NU/Kg) on hot-plate latency in rats with no lesion, noradrenergic neuron depletion and both noradrenergic and serotonergic neuronal depletion were studied, respectively. Rats in each group were subdivided equally to 2 subgroups: saline and neurotropin. After completion of the hot-plate tests, each rat was decapitated, the cerebral cortex was dissected from its internal structure for measurement of norepinephrine contents. Hot-plate latency significantly decreased by ∼40% 10 days after ip DSP-4 or after ip DSP-4 and 5,7-DHT. Norepinephrine contents in DSP-4 treated rats (55.6±6.3ng/ng tissue) and DSP-4+5,7-DHT treated rats (35.3±6.3ng/ng tissue) were significantly lower than those in intact rats (131.6±5.7ng/ng tissue, p<0.01). Neurotropin significantly increased the area under the curve (AUC) of the hot-plate latency in the DSP-4 and DSP-4+5,7-DHT groups but not in the Sham group. There was a significant correlation between AUC and norepinephrine contents in saline subgroup (p<0.01, r=0.597) but not in neurotropin subgroup in DSP-4 group. Neurotropin exerted an antinociceptive effect in DSP-4 induced central neuropathic pain. The present data suggest neuronal pathways other than descending inhibitory noradrenergic and serotonergic systems may be involved in neurotropin mediated antinociception.
authors.affiliation: Department of Anesthesiology, Hirosaki University Graduate School of Medicine, 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: D015116:5,7-Dihydroxytryptamine / Q000633:toxicity; D018663:Adrenergic Agents / Q000633:toxicity*; D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D019540:Area Under Curve; D001596:Benzylamines / Q000633:toxicity*; D004195:Disease Models, Animal; D004563:Electrochemistry; D008125:Locus Coeruleus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009437:Neuralgia / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D009638:Norepinephrine / Q000031:analogs & derivatives* / Q000378:metabolism; D010147:Pain Measurement; D011134:Polysaccharides / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D018490:Serotonin Agents / Q000633:toxicity
chemical_list: D018663:Adrenergic Agents; D000700:Analgesics; D001596:Benzylamines; D011134:Polysaccharides; D018490:Serotonin Agents; D015116:5,7-Dihydroxytryptamine; C002748:noradrenalone; C010491:neurotropin; C012102:DSP 4; D009638:Norepinephrine