Journal
PAIN
Volume 117, Issue 1-2, Pages 112-120Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.pain.2005.05.026
Keywords
vincristine; neuropathy; NO/cGMP pathway; NO synthase; hyperalgesia
Categories
Ask authors/readers for more resources
The mechanisms that underlie the development of vincristine-induced painful neuropathy are poorly understood. The nitric oxide (NO)cGMP pathway has been reported to be involved in the spinal transmission of nociceptive information. In the present study, we examined whether alterations in spinal nociceptive processing via the NO-cGMP pathway contribute to vincristine-induced painful neuropathy in mice. Mice were intraperitoneally treated with vincristine at a dose of 0.05 mg/kg 1 day after the measurement of pre-drug latency in the tail-flick test, and then treated with a dose of 0.125 mg/kg twice a week for 6 weeks. In vincristine-treated mice, a significant decrease in tail-flick latencies developed at 4 weeks after treatment. Pretreatment with L-arginine (30-300 mg/kg, s.c.), a substrate of NO synthase (NOS), dose-dependently increased the tail-flick latencies in vincristine-treated mice. The L-arginine-induced increase in tail-flick latencies in vincristinetreated mice was completely reversed by i.t. pretreatment with N-G-nitro-(L)-arginine methyl ester ((L)-NAME, 3-30 nmol), a NOS inhibitor. Furthermore, i.t. pretreatment with 8-bromoguanosine 3 ', 5 '-cyclic monophosphate (8-Br-cGMP, 0.3-3.0 nmol), a membrane-permeable cGMP analog, dose-dependently increased the tail-flick latencies in vincristine-treated mice. The contents of NO metabolites, cGMP and protein levels of neuronal NOS in the spinal cord in vincristine-treated mice were significantly reduced compared to those in vehicle-treated naive mice. These results indicate that dysfunction of the (L)-arginine/NO/cGMP cascade in the spinal cord may trigger vincristine-induced thermal hyperalgesia in mice. (c) 2005 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available