Anti-tumor necrosis factor (anti-TNF) agents rapidly reduce pain perception in brains of patients with Crohn’s disease, researchers show in the October issue of Gastroenterology. This observation could explain how clinical disease activity is often reduced long before signs of mucosal healing.
Patients with Crohn’s disease treated with anti-TNF agents often report reductions in abdominal pain within few days. This is surprising, because the pain is caused by mucosal inflammation and structural bowel damage, which don’t begin to heal until about 2 weeks after anti-TNF therapy begins.
TNF has been implicated as a pain mediator, due to its involvement in mechanical hyperalgesia after injury. Andreas Hess et al performed a functional imaging study to determine whether the ability of anti-TNF drugs to provide rapid relief of abdominal pain could involve altered pain perception.
Hess et al visualized activity patterns of cerebral pain caused by repeated compression of the lower right abdomen in patients before, 24 hours after, and 27 days after administration of anti-TNF (infliximab 5 mg/kg, given intravenously), using blood oxygen level-dependent functional magnetic resonance imaging (fMRI) analysis.
The authors visualized activity in somatosensory regions of the brain upon finger tapping (control, green) and abdominal compression (red). In 3 patients who responded to anti-TNF therapy, based on Harvey–Bradshaw Index scores, activity in somatosensory regions of brain decreased as early as 24 hours after the first anti-TNF administration (middle column, red), and further decreased after 28 days (right column, red). In contrast, signals elicited by finger tapping did not change over the time course.
In the single patient that did not respond to anti-TNF therapy, there was only slight reduction in signal 24 hours after drug administration, which then even exceeded the baseline level after 28 days.
The authors conclude that TNF mediates pain perception in the brain, which is quickly reduced upon TNF inhibition in patients who respond to this therapy.
Hess et al discuss their findings in a video abstract: