The gastrointestinal barrier is - with approximately 400 m2 - the human body’s largest surface separating the external environment from the internal milieu. This barrier serves a dual function: permitting the absorption of nutrients, water and electrolytes on the one hand, while limiting host contact with noxious luminal antigens on the other hand. To maintain this selective barrier, junction protein complexes seal the intercellular space between adjacent epithelial cells and regulate the paracellular transport. Increased intestinal permeability is associated with and suggested as a player in the pathophysiology of various gastrointestinal and extra-intestinal diseases such as inflammatory bowel disease, celiac disease and type 1 diabetes. The gastrointestinal tract is exposed to high levels of endogenous and exogenous proteases, both in the lumen and in the mucosa. There is increasing evidence to suggest that a dysregulation of the protease/antiprotease balance in the gut contributes to epithelial damage and increased permeability. Excessive proteolysis leads to direct cleavage of intercellular junction proteins, or to opening of the junction proteins via activation of protease activated receptors. In addition, proteases regulate the activity and availability of cytokines and growth factors, which are also known modulators of intestinal permeability. This review aims at outlining the mechanisms by which proteases alter the intestinal permeability. More knowledge on the role of proteases in mucosal homeostasis and gastrointestinal barrier function will definitely contribute to the identification of new therapeutic targets for permeability-related diseases.

BACKGROUND Intermediate nerve neuralgia is a rare type of cranial neuralgia that causes clinical, therapeutic, and diagnostic challenges. Studies have described pharmacological and surgical treatment options. Surgical treatment ranges from sectioning of neural structures to microvascular decompression. Given the rareness of the disease, there are no clear recommendations concerning treatment. OBSERVATIONS Reported is the case of a patient with typical intermediate nerve neuralgia. In this particular case, decision-making toward surgical decompression in an earlier stage of the disease could have been beneficial. The authors found excellent results using only microvascular decompression without sectioning of neural structures. LESSONS Knowledge of intermediate nerve anatomy is essential to understand this complex pain syndrome. This case illustrates that surgery should not only be regarded as a last resort in case of failure of conservative treatment but also should be considered early in the disease course, especially in the case of a clear neurovascular conflict. When no evident cause is found, surgery could be considered as an exploratory option to depict a neurovascular conflict intraoperatively. Microvascular decompression of the intermediate nerve without sectioning of neural structures can obtain excellent results. Since neural structures are saved, postoperative sequelae can be limited.