Microglial activation in the trigeminal spinal subnucleus interpolaris/caudalis modulates orofacial incisional mechanical pain hypersensitivity associated with orofacial injury in infancy

Purpose: Infantile tissue injury induces sensory deficits in adulthood. Infantile facial incision (IFI) was reported to cause an enhancement of incision-induced mechanical hypersensitivity in adulthood due to acceleration of the trigeminal ganglion neuronal excitability. However, the effects of IFI on activation of microglia in the spinal trigeminal nucleus and its involvement in facial pain sensitivity is not well known. Methods: A facial skin incision was made in the left whisker pad in infant (IFI) and/or adult rats (AFI). Mechanical head withdrawal threshold and microglial activation in the trigeminal spinal nucleus were analyzed. Results: Mechanical pain hypersensitivity induced by AFI was significantly exacerbated and prolonged by IFI. The number of Iba1-immunore-active cells in the trigeminal spinal nucleus following AFI was increased by IFI, suggesting that IFI facilitates microglial hyperactivation following AFI. Intraperitoneal administration of minocycline, a microglial activation inhibitor, suppressed the facial incision-induced microglial hyperactivation in the trigeminal spinal nucleus and the exacerbation of the facial mechanical pain hypersensitivity induced by IFI. Conclusion: These results suggest that facial trauma in infants causes hyperactivation of microglia in the trigeminal spinal nucleus following AFI, leading to the prolongation of the facial mechanical pain hypersensitivity.