Non-serotonergic midbrain neurons are involved in picrotoxin-induced analgesia. An immunohistochemical study in the rat.

Intravenous picrotoxin inhibits spinal nociceptive neurons through disinhibitory activation of neurons in the periaqueductal gray (PAG) and nucleus raphe dorsalis (NRD), where the descending antinociceptive system arises. We found Fos-like immunoreactivity in PAG/NRD neurons after intravenous injection of picrotoxin. This distribution of c-Fos expression is consistent with a role of PAG/NRD for antinociception; neurons with intense Fos-like immunoreactivity was also clustered in the Edinger-Westphal nucleus (EW). Double fluorescence immunohistochemistry for c-Fos and serotonin revealed that PAG/NRD/EW neurons expressing c-Fos were non-serotonergic. These data suggest that non-serotonergic PAG/NRD/EW neurons are involved in the picrotoxin-induced analgesia.