Figure 7.

A model of the proposed mechanism of common pancreatic-bile duct ligation on pancreatic inflammation. Duct obstruction causes the release of LTB₄ locally within the pancreas. LTB₄stimulates TRPV1 expressed in the plasma membrane of primary sensory nerves innervating the parenchyma of the gland. When stimulated, TRPV1 depolarizes the neurons resulting in the propagation of orthograde action potentials causing the release of proinflammatory neurotransmiters such as substance P (SP) in the pancreas to cause damage and retrograde action potentials causing the release of nociceptive neurotransmitters in the spinal cord to cause pain. The TRPV1 antagonist, capsazepine, blocks LTB₄ stimulation of TRPV1. MK-886 reduces LTB₄ levels by inhibiting 5-lipoxygenase activating peptide (FLAP). Both capsazepine and MK-886 ameliorate duct obstruction-induced pancreatitis. For simplicity and clarity, other mechanisms that may be involved in these processes such as protease activated receptor-2 (PAR2) activation of TRPV1 and co-release of calcitonin gene-related peptide (CGRP) with substance P have been omitted.