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

摘要

Electrical stimulation of the secondary somatosensory cortex (S-II), which is clinically effective in some chronic pain patients, produces a weak antinociception by itself and also strongly facilitates the antinociceptive effect of the neuronal NO synthase inhibitor 7-nitro-indazole in laboratory animals (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, although 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 synergistic antinociception exerted by S-II stimulation in combination with 7-nitro-indazole was resistant to systemic administration of the opioid antagonist naloxone or the alpha-adrenoceptor antagonist phentolamine. In contrast, intrathecally administered methysergide, a serotonin receptor antagonist, at 20 microg/rat, abolished the first-phase, but not the second-phase, antinociception following S-II stimulation in combination with 7-nitro-indazole. These findings suggest that S-II stimulation, in combination with inhibition of neuronal NO synthase, can suppress spinal nociceptive neurons, at least in part through the descending spinal serotonergic pathway, resulting in antinociception.