EGF and gastrointestinal disease: Although EREG is the most investigated EGFR ligand in the context of pain,115,116,119 EGF and HB-EGF administrations were shown to evoke pain responses as well.116,120 Accordingly, evidence suggests that the targeting of EGFR may alleviate pain in humans121–124 and animals.115–117,125,126 However, no reports exist about EGFR targeting in visceral pain conditions, making EGF signaling an attractive therapeutic target for painful gastrointestinal diseases.