Increased Expression of Brain-derived Neurotrophic Factor in Irritable Bowel Syndrome and Its Correlation With Abdominal Pain (Gut 2012;61:685-694)

Abstract

Patients with irritable bowel syndrome (IBS) commonly present with abdominal pain associated with altered bowel habit. Abdominal pain is the symptom most likely to result in medical consultation in IBS patients.1,2 Brain-derived neurotrophic factor (BDNF), a member of neurotrophin family, is produced in the central nervous system microglia in response to noxious stimuli and associated with pain modulation and central sensitization. There are large evidences that BDNF may play an important role in visceral pain and hypersensitivity states.3-6 Recently, Yu et al7 investigated the impact of BDNF expression on altered gut sensation in patients with IBS. First, this study was performed in colonic biopsies from 40 patients with IBS and 21 healthy controls. A significant increase in the expression of BDNF and nerve fibers was found in colonic biopsies from patients with IBS, compared with healthy controls. No significant difference was observed in the expression of BDNF and nerve fibers between the IBS subgroups. Transmission electron microscopy showed the ultrastructural damage of nerve axons in the colonic mucosa of patients with IBS. Also, increased expression of BDNF correlated significantly with the severity and frequency of abdominal pain/discomfort in patients with IBS. Next, animal studies using BDNF+/- and BDNF+/+ mice were performed to evaluate the role of BDNF in visceral hypersensitivity. The visceral response to colorectal distention (CRD) was evaluated by abdominal withdrawal reflex (AWR) scores. The AWR scores were significantly lowered in BDNF+/- mice at 45 and 60 mmHg CRD pressures applied. The mucosal protein gene product 9.5 was significantly lowered in BDNF+/- mice. Intraperitoneal injection of BDNF induced a significant dose-dependent decrease in threshold pressure and an increased expression of the post-synaptic tyrosine protein kinase B (TrkB) receptor in the dorsal root ganglia of BDNF+/+ mice. Transmission electron microscopy showed the degenerative changes of nerve axons and Schwann cells in BDNF+/- mice. The authors concluded that the increased expression of BDNF with ultrastructural alterations of nerve innervation in the colonic mucosa may contribute to the visceral hyperalgesia in patients with IBS.