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.