Five patients complaining of severe pain due to severe post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) underwent nasopancreatic drainage (NPD) placement. Pain relief was achieved on the second, fourth, and fifth day in three, one, and one patients, respectively. Four patients underwent pancreatic juice culture; all were positive. Our results suggest that NPD can relieve severe PEP with severe pain. Bacteria-induced protease-activated receptor-2 activation may be associated with PEP.