Ocular inflammation induces trigeminal pain, peripheral and central neuroinflammatory mechanisms

Pierre-Serge Launay (1) , Elodie Reboussin (1) , Hong Liang (1, 2) , Karima Kessal (1) , David Godefroy (1) , William Rostene (1) , José-Alain Sahel (1, 2) , Christophe Baudouin (1, 2) , Stéphane Melik Parsadaniantz (1) , Annabelle Reaux Le Goazigo (1)

1 Institut de la Vision
2 CHNO - Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts

Ocular surface diseases are among the most frequent ocular pathologies, with prevalence ranging from 20% of the general population. In addition, ocular pain following corneal injury is frequently observed in clinic. The aim of the study was to characterize the peripheral and central neuroinflammatory process in the trigeminal pathways in response to cornea alteration induced by chronic topical instillations of 0.2% benzalkonium chloride (BAC) in male C57BL/6 J mice. In vitro BAC induced neurotoxicity and increases neuronal (FOS, ATF3) and pro-inflammatory (IL-6) markers in primary mouse trigeminal ganglion culture. BAC-treated mice exhibited 7 days after the treatment reduced aqueous tear production and increased inflammatory cell infiltration in the cornea. Hypertonic saline-evoked eye wipe behavior was enhanced in BAC-treated animals that exhibited increased FOS, ATF3 and Iba1 immunoreactivity in the trigeminal ganglion. Ocular inflammation is associated with a significant increase in IL-6 and TNF-α mRNA expression in the trigeminal ganglion. We reported a strong increase in FOS and Iba1 positive cells in particular in the sensory trigeminal complex at the ipsilateral interpolaris/caudalis (Vi/Vc) transition and Vc/upper cervical cord (Vc/C1) regions. In addition, activated microglial cells were tightly wrapped around activated FOS neurons in both regions and phosphorylated p38 mitogen-activated protein kinase was markedly enhanced specifically in microglial cells during ocular inflammation. Similar data were obtained in the facial motor nucleus. These neuroanatomical data correlated with the increase in mRNA expression of pro-inflammatory (TNF-α, IL-6, CCL2) and neuronal (FOS and ATF3) markers. Interestingly, the suppression of corneal inflammation 10 days following the end of BAC treatment resulted in a marked attenuation of peripheral and central changes observed in pathological conditions.

Mots clés: benzalkonium chloride; corneal neurons; ocular pain; neuroinflammation; trigeminal complex; facial motor nucleus

Domaines: Neurobiologie

Pierre-Serge Launay, Elodie Reboussin, Hong Liang, Karima Kessal, David Godefroy, et al.. Ocular inflammation induces trigeminal pain, peripheral and central neuroinflammatory mechanisms. Neurobiology of Disease, 2016, 88, pp.16-28. ⟨10.1016/j.nbd.2015.12.017⟩. ⟨hal-01258703⟩