Abstract # 1835 Corneal injury induces trigeminal pain, peripheral and central neuroinflammatory process

Ocular surface diseases are among the most frequent ocular pathologies, with prevalence ranging from 20% of the general population. Ocular pain following corneal injury is frequently observed in clinic. Here we characterized the peripheral and central neuroinflammatory process in the trigeminal pathways in response to ocular pain. We used topical instillations of 0.2% benzalkonium chloride (BAC) in mice for 7 days. BAC-treated animals developed severe dry eye (reduced tear production and inflammation in the cornea). Hypertonic saline-evoked eye wipe behavior was enhanced in BAC-treated animals. We reported an increased ATF3, FOS and Iba1 immunoreactivity and higher IL-6 and TNF- α mRNA levels in the trigeminal ganglion. Interestingly, the sensory trigeminal complex at the ipsilateral interpolaris/caudalis (Vi/Vc) transition and Vc/upper cervical cord (Vc/C1) regions exhibited higher FOS and Iba1 positive cells in BAC animals. Activated microglial cells were tightly wrapped around activated FOS neurons in both regions. Furthermore, phosphorylated p38 MAPK was markedly enhanced in microglial cells during ocular inflammation. These neuroanatomical data correlated with the increase in mRNA expression of pro-inflammatory (TNF- α , IL-6, CCL2) and neuronal (FOS and ATF3) markers. This work provides the demonstration that corneal inflammation provokes central neuroinflammatory process. Thus, altered activity in intracellular signaling caused by ocular inflammation might play a priming role in the central sensitization of ocular related brainstem circuits, which represents a significant factor in ocular pain development.