Involvement of TNFα in the enhancement of hypersensitivity in the adulthood-injured face associated with facial injury in infancy.

To evaluate the mechanisms underlying acceleration of hypersensitivity in the adulthood-injured face following facial injury in infants, we developed the rats model with facial skin injury in infants and adulthoods (incision + incision), and facial skin suture in infants and facial skin injury in adulthoods (sham + incision), and analyzed the mechanical head-withdrawal threshold (MHWT) of the facial skin, immunohistochemical analysis of trigeminal ganglion (TG) and the effects of intra-ganglionic administration of neutralizing ant-TNFα antibody and recombinant TNFα on nocifensive behavior. The MHWT became considerably lower in incision + incision rats than in sham + incision rats at 10-14 days after the surgery. We observed many TG neurons encircled by glial fibrillary acidic protein-immunoreactive (GFAP-IR) cells and those exhibited TNFα immunoreactivity. TNFα was also expressed in GFAP-IR cells in incision + inicision TG. TNFα protein levels and the relative number of TNFα-IR cells were significantly higher in incision + incision rats than in sham + incision rats. The MHWT was significantly recovered during the intra-ganglionic administration of neutralizing anti-TNFα antibody 4-14 days after the incision. Furthermore, the MHWT was significantly decreased in sham + incision rats following the intra-ganglionic administration of recombinant TNFα. The present findings suggest that the neuron-satellite glial cell communication via TNFα is a critical mechanism in the enhancement of mechanical hypersensitivity in the adulthood-injured face following facial injury in infants.