Sustained microglial immunoreactivity in the caudal spinal trigeminal nucleus after formalin injection

Recent studies indicate that glia may be involved in altered nociceptive processing after a peripheral inflammatory lesion produced by injection of inflammatory reagents such as formalin and zymosan. Most of these studies, however, confined their observations to a period shortly after the injections. This study investigated the immunohistochemical responses of microglia in the caudal part of the spinal trigeminal nucleus for up to 60 days after subcutaneous injection of formalin into the lateral faces of Wistar rats. The results showed obvious up-regulation of microglial markers such as OX-18, OX-42 and OX-6 up to 21 days after formalin injection. These were somewhat reduced at 30 days after injection. Electron microscope investigation revealed no evidence of significant phagocytosis of degenerative neuronal elements by microglia in the nucleus at the time--that is, 7 days after formalin injection, when microglial activation was at its peak. Significantly, however, the period of microglial activation corresponded closely to that showing enhanced nociceptive behavior after perioral formalin injection (Cadet et al., 1995). This study indicates a microglial role in the genesis of enhanced nociceptive behavior.