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

The intrathecal (i.t.) administration of glutamate (10-100 nmol) caused dos e-related hyperalgesia (mean ED50 of 35 nmol) when assessed in the thermal behaviour model of nociception, the hot-plate test maintained at 50 degrees . The i.p., i.t. or intracerebroventricular (i.c.v.) injection of the nitri c oxide synthase inhibitors, L-NOARG and L-NAME, did not induce any detecta ble effect per se, but instead, produced dose-related inhibition of glutama te-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 attenuatio n of glutamate-induced hyperalgesia. L-arginine (3.4 mmol kg(-1), i.p.), bu t not D-arginine (3.4 mmol kg(-1), i.p.) significantly potentiated glutamat e (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 mu mol) or 8-bromo-cGMP (22.5 nmol) with glutamate (10 nmol), via either i.t. or i.c.v. routes, also significantly enhanced glutamate-ind uced hyperalgesia. The guanylate cyclase inhibitors LY 83583 (0.1-1.0 nmol) or ODQ (30-300 pmol) co-administered with glutamate, dose-dependently anta gonised the glutamate-induced hyperalgesia. Collectively, these results dem onstrate that the i.t. injection of glutamate into the spinal cord of mice produces dose-related hyperalgesia an effect that was largely mediated by t he L-arginine-nitric oxide-cGMP pathway from both spinal and supraspinal si tes. (C) 1999 Elsevier Science Ltd. All rights reserved.