Secondary somatosensory cortex stimulation facilitates the antinociceptiveeffect of the NO synthase inhibitor through suppression of spinal nociceptive neurons in the rat

Electrical stimulation of the secondary somatosensory cortex (S-II), which is clinically effective in some chronic pain patients, produces a weak anti nociception by itself and also strongly facilitates the antinociceptive eff ect of the neuronal NO synthase inhibitor 7-nitro-indazole in laboratory an imals (rats). The present study thus investigated the mechanisms by which S -II stimulation facilitates the 7-nitro-indazole-induced antinociception. S -II stimulation in combination with 7-nitro-indazole at a subeffective dose , 5 mg/kg, synergistically reduced the number of cells expressing c-Fos in response to intraplantar injection of formalin in the superficial regions ( laminae I and II) of the L4 and L5 spinal dorsal horn in conscious rats, al though each had no significant effect. A similar synergism produced by S-II stimulation and 7-nitro-indazole was also confirmed in both the first and second phases in the formalin-induced behavioral nociception test. The syne rgistic antinociception exerted by S-II stimulation in combination with 7-n itro-indazole was resistant to systemic administration of the opioid antago nist naloxone or the alpha -adrenoceptor antagonist phentolanline. In contr ast, intrathecally administered methysergide, a serotonin receptor antagoni st, at 20 mug/rat. abolished the first-phase, but not the second-phase, ant inociception following S-II stimulation in combination with 7-nitro-indazol e. These findings suggest that S-II stimulation, in combination with inhibi tion of neuronal NO synthase, can suppress spinal nociceptive neurons, at l east in part through the descending spinal serotonergic pathway, resulting in antinociception. (C) 2001 Elsevier Science B.V. All rights reserved.