Intrathecal injection of N-methyl-d-aspartate (NMDA) induces a short duration hyperalgesia in mice. An inhibitor of nitric oxide synthase (NOS), Nω-nitro-l-arginine methyl ester (l-NAME), administered either systemically or intrathecally, blocked the NMDA-induced hyperalgesia. This effect was partially reversed by the NOS substrate, l-arginine. Intrathecal hemoglobin mimicked the effects of l-NAME. Intrathecal injection of the NO-donating compounds, sodium nitroprusside (SNP) and hydroxylamine, resulted in a hyperalgesia that lasted 3 h and was reduced by coadministration of hemoglobin. Thus, nitric oxide production appears to mediate NMDA-induced hypersensitivity and may contribute to other forms of centrally induced hyperalgesia.
Bibliographical noteFunding Information:
The authors wish to thank Dr. Leonard Lichtblau for expert assistance with the data analysis. This work was supported by USPHS Grants R01-DA-04274, R01-DA-01933 and K-02-DA-00145 to G.L.W.
- Nitric oxide
- Sodium nitroprusside
- Synaptic plasticity