The role of systemic, spinal and supraspinal L-arginine-nitric oxide-cGMP pathway in thermal hyperalgesia caused by intrathecal injection of glutamate in mice.

Abstract

The intrathecal (i.t.) administration of glutamate (10-100 nmol) caused dose-related hyperalgesia (mean ED50 of 35 nmol) when assessed in the thermal behaviour model of nociception, the hot-plate test maintained at 50 degrees C. The i.p., i.t. or intracerebroventricular (i.c.v.) injection of the nitric oxide synthase inhibitors, L-NOARG and L-NAME, did not induce any detectable effect per se, but instead, produced dose-related inhibition of glutamate-induced hyperalgesia. D-NAME, the inactive enantiomer of L-NAME, had no effect. The i.c.v. or i.t. administration of L-NIO caused graded attenuation of glutamate-induced hyperalgesia. L-arginine (3.4 mmol kg(-1), i.p.), but not D-arginine (3.4 mmol kg(-1), i.p.) significantly potentiated glutamate (10 nmol)-induced hyperalgesia, an action that was prevented by L-NOARG (137 nmol kg(-1)). The co-injection of S-nitroso-N-acetyl-D,L-penicillamine (SNAP) (0.22 micromol) or 8-bromo-cGMP (22.5 nmol) with glutamate (10 nmol), via either i.t. or i.c.v. routes, also significantly enhanced glutamate-induced hyperalgesia. The guanylate cyclase inhibitors LY 83583 (0.1-1.0 nmol) or ODQ (30-300 pmol) co-administered with glutamate, dose-dependently antagonised the glutamate-induced hyperalgesia. Collectively, these results demonstrate that the i.t. injection of glutamate into the spinal cord of mice produces dose-related hyperalgesia an effect that was largely mediated by the L-arginine-nitric oxide-cGMP pathway from both spinal and supraspinal sites.

• Authors: J Ferreira, A R Santos, J B Calixto
• Journal: Neuropharmacology (Neuropharmacology) Vol. 38 Issue 6 Pg. 835-42 (Jun 1999) ISSN: 0028-3908 [Print] England
• PMID: 10465687 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• Nitroarginine
• Nitric Oxide
• Glutamic Acid
• Arginine
• Nitric Oxide Synthase
• Cyclic GMP
• NG-Nitroarginine Methyl Ester

Topics

• Analysis of Variance
• Animals
• Arginine (physiology)
• Cyclic GMP (physiology)
• Enzyme Inhibitors (pharmacology)
• Glutamic Acid (pharmacology)
• Hot Temperature
• Hyperalgesia (etiology, physiopathology)
• Injections, Intraperitoneal
• Injections, Intraventricular
• Injections, Spinal
• Male
• Mice
• NG-Nitroarginine Methyl Ester (pharmacology)
• Nitric Oxide (physiology)
• Nitric Oxide Synthase (antagonists & inhibitors)
• Nitroarginine (pharmacology)