Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9429104 | Neuroscience Letters | 2005 | 5 Pages |
Abstract
We have investigated the effect of treatment with NÏ-nitro-l-arginine methylester (l-NAME), a non-selective nitric oxide synthase inhibitor (NOS), both before and after the induction of mechanical allodynia by tight ligation of the left L5 and L6 spinal nerves in rats (SNL rats). The degree of mechanical allodynia was measured by tactile threshold for paw flinching with von Frey filaments. Intraperitoneal (i.p.) administration of l-NAME (3-30Â mg/kg) 1 week after the spinal nerve ligation produced a dose-dependent reduction of the behavioral signs of mechanical allodynia, but the effect was not reversed by pretreatment with l-arginine (300Â mg/kg). NÏ-Nitro-l-arginine (l-NNA, i.p., 30Â mg/kg), aminoguanidine (AG, i.p., 30Â mg/kg) and a potent neuronal NOS inhibitor (LY457963, i.p., 30Â mg/kg) did not reduce mechanical sensitivity in the SNL rats. Furthermore, using an ex vivo NOS activity assay, l-NAME partially inhibited the spinal NOS activity, whereas LY457963 almost completely inhibited the spinal NOS activity. Prior administration of l-NAME (i.p., 30Â mg/kg) or of MK-801 (0.5Â mg/kg), an NMDA antagonist, 30Â min before the spinal nerve ligation significantly prevented the development of mechanical allodynia after spinal nerve ligation for an extended period of time. High doses of l-arginine (100Â mg/kg or 300Â mg/kg, i.p.), however, did not reverse the preemptive effect of l-NAME. These results suggest that neither the anti-allodynic nor the preemptive effects of l-NAME are mediated by NOS inhibition.
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Authors
Doo H. Lee, Jai Pal Singh, David Lodge,