Abstract
Obstructive bowel disorders (OBD) are characterized by lumen distention due to mechanical or functional obstruction in the gut. Abdominal pain is one of the main symptoms in OBD. In this article, we aim to critically review the potential mechanisms for acute and chronic pain in bowel obstruction (BO). While clustered contractions and associated increase of intraluminal pressure may account for colicky pain in simple obstruction, ischemia may be involved in acute pain in severe conditions such as closed loop obstruction. Recent preclinical studies discovered that visceral sensitivity is increased in BO, and visceral hypersensitivity may underlie the mechanisms of chronic abdominal pain in BO. Mounting evidence suggests that lumen distension, as a circumferential mechanical stretch, alters gene expression (mechano-transcription) in the distended bowel, and mechano-transcription of nociceptive and inflammatory mediators plays a critical role in the development of visceral hypersensitivity in BO. Mechano-transcription of nerve growth factor (NGF) in gut smooth muscle cells is found to increase voltage-gated Na+ channel (Nav) activity of the primary sensory neurons by up-regulating expression of TTX-resistant Nav1.8, whereas mechanical stretch-induced brain-derived neurotrophic factor (BDNF) reduces Kv currents especially A-type (IA) currents by down-regulating expression of specific IA subtypes such as Kv1.4. The NGF and BDNF mediated changes in gene expression and channel functions in the primary sensory neurons may constitute the main mechanisms of visceral hypersensitivity in OBD. In addition, mechanical stretch-induced COX-2 and other inflammatory mediators in the gut may also contribute to abdominal pain by activating and sensitizing nociceptors.
Highlights
Obstructive bowel disorders (OBD) are characterized by lumen distention due to mechanical or functional obstruction
We found that gene expression of several well-recognized pain mediators, i.e., cyclo-oxygenase-2 (COX-2), nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), was significantly up-regulated in the distended colon
Multiple mechanisms may account for abdominal pain in bowel obstruction (BO)
Summary
Obstructive bowel disorders (OBD) are characterized by lumen distention due to mechanical or functional obstruction. Mechanical bowel obstruction (BO) is the prototype of OBD, and constitutes more than 300,000 admissions annually in the United States alone. It is responsible for nearly 30,000 deaths and direct costs of more than $3 billion in. Patients present with lumen distention and obstructive symptoms similar to mechanical obstruction. The main symptoms of OBD are abdominal pain, distention, nausea, vomiting, and constipation (Gore et al, 2015). Among patients with malignant obstruction, 92% have distention-associated chronic abdominal pain (Baines et al, 1985). We will offer novel insights into the mechanisms of visceral hypersensitivity in obstruction
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