The viscera, or internal organs, of the GI tract are innervated by the autonomic nervous system, which includes the enteric, sympathetic, and parasympathetic nervous systems.³ The enteric system is built into the walls of the GI tract, consisting of the myenteric (Auerbach) plexus between smooth muscle layers and the submucosal (Meissner) plexus. They function to regulate motility, secretion, and perfusion and are under modulation by the sympathetic and parasympathetic nervous systems. Sympathetic stimulation predominately inhibits GI function, such as decreased peristalsis, decreased luminal secretions, and vasoconstriction of intestinal vascular beds. The preganglionic sympathetic nerve fibers come from the intermediolateral nuclei of the thoracolumbar spinal cord (T5-L2). Most of these fibers synapse within the sympathetic chain, but a subset bypasses the sympathetic chain forming splanchnic nerves and synapses in groups of ganglia at the anatomical midline, such as the celiac plexus. The respective postganglionic sympathetic nerve fibers ultimately synapse at the target GI viscera, including the enteric plexuses. Conversely, the parasympathetic nervous system predominantly stimulates GI function, such as increased peristalsis and secretions, sphincter relaxation, and vasodilation of intestinal vascular beds. Preganglionic parasympathetic fibers, sometimes referred to as the craniosacral outflow, either travel within the vagus nerve for the proximal GI tract or arise from the lateral gray horn of the sacral cord forming the pelvic splanchnic nerve for the distal GI tract.¹ These fibers then synapse onto ganglia adjacent to the target organ within the myenteric and submucosal plexuses (Fig. 18.1).

Visceral pain is derived from noxious stimuli within the organs themselves and transmitted by the autonomic nervous system. Pain signals of the GI tract are first sensed by the free nerve endings of afferent A-δ and unmyelinated C fibers within the connective tissue of visceral organs.⁴ These afferent fibers travel predominately within sympathetic fibers, splanchnic nerves, and their respective sympathetic plexuses and synapse onto the dorsal horn of the spinal cord. The cell body of such afferent fibers is found within the dorsal root ganglion. The dorsal horn is a critical junction whereby afferent pain signals are constantly modulated by the local and descending interneuron activities. From here, the second-order projections form ascending afferent bundles to the brainstem and diencephalon structures such as the thalamus, hypothalamus, periaqueductal gray, and reticular formation. The spinothalamic tract is one such pain pathway (see Fig. 18.1). Finally, the third-order neurons in the thalamus send projections onto the somatosensory cortex.

As mentioned, visceral pain is primarily mediated by sympathetic nerve pathways. There is some contribution to pain signaling in the distal GI tract, namely the distal colon and rectum, via the parasympathetic pelvic splanchnic nerve.¹ However, the parasympathetic system serves a more physiological role, with afferents signaling fullness, nausea, and distention, and efferents promoting secretions, motility, and sphincter relaxation. This is primarily mediated by the vagus nerve.

Somatic pain is caused by noxious stimuli to superficial structures including the parietal peritoneum, abdominal wall muscles, and skin. Somatic pain is sensitive to crushing and cutting types of injury, whereas visceral pain is primarily induced by inflammation, ischemia, and distention.⁵ Somatic pain is also transmitted by free nerve endings of afferent A-δ and C fibers but in a denser distribution and hence better localized than visceral pain. Somatic afferent fibers are carried by the ventral rami of thoracoabdominal nerves rather than with the
sympathetic pathway, demonstrating why visceral pain stimuli are associated with emotional disturbances and autonomic dysregulation such as nausea. From the spinal cord, somatic pain signals share the same ascending tracts as visceral signals.⁵

The convergence of somatic and visceral pain afferents at the level of the spinal cord gives rise to a phenomenon known as referred pain.⁵ Defined as pain experienced at a site distant from the noxious stimulus, this process is mediated by somatic and visceral afferents forming synapses onto the same interneuron of the dorsal horn (see Fig. 18.1). A classic example can be illustrated by myocardial ischemia (visceral stimulus) presenting as pain in the left arm (somatic sensation).

Inflammation is a complex immunological process in response to tissue injury or infection and accounts for a majority of acute abdominal pain syndromes (Table 18.1). The inflammatory process involves an intricate interplay of cells and chemical mediators to protect and repair the damaged site. This process causes several unwanted effects including redness, swelling, heat, and pain. These signs of inflammation are largely a consequence of vasodilation and increased blood flow to the damaged tissue in order to deliver repair factors. Pain, on the other hand, is thought to be an adaptive mechanism to encourage immobility and ultimately facilitate repair.⁶ Several inflammatory mediators are responsible for transmission of pain. Initially, local macrophages release acute phase reactants bradykinin and TNF-α upon tissue injury. It is well established that bradykinin, a nine-amino acid peptide, is a primary mediator of inflammatory hyperalgesia via activation of B1 and B2 receptors of sensory afferent nerve endings. Interestingly, B2 receptors are constitutively expressed, whereas B1 receptors are inducible in the presence of cytokines, endotoxins, and injured tissues.⁷ TNF-α, on the other hand, initiates a cascade of interleukin synthesis and release including IL-6, IL-1, and IL-8, appropriately creating a milieu of inflammatory mediators. IL-6 and IL-1β upregulate prostaglandins by inducing arachidonic acid availability and cyclooxygenase-2 (COX-2) activity. IL-8 stimulates release of adrenergic amines such as norepinephrine. Both prostaglandins and adrenergic amines are implicated in lowering the threshold for pain transmission at sensory afferents.⁶

Ischemic pain is primarily caused by inadequate oxygen delivery. This is most often encountered in peripheral vascular diseases; however, mesenteric ischemia is a diagnosis associated
with severe GI pain. At the cellular level, a lack of oxygen halts the electron transport chain and oxidative phosphorylation of ATP. Without ATP, the sodium-potassium pump fails to maintain a proper electrochemical gradient leading to membrane damage and reactive oxygen species formation.⁸ In addition, hypoxia leads to anaerobic metabolism and lactic acidosis. Sensory A-δ and C fibers are stimulated by acidosis via a H⁺-gated cation channel termed ASIC (acidsensing ion channel).⁹ Various metabolites involved in ischemia including lactate, ATP, ADP, and free radicals can further sensitize afferent fibers to noxious stimuli.¹⁰ Finally, ischemic tissue injury elicits a local cytokine response, and inflammatory mechanisms described above likely contribute to ischemic pain.

The last source of GI pain comes from the distention and stretch of tissue. This is perhaps best demonstrated by an obstructed lumen and subsequent distention of the organ walls proximal to the obstruction, such as a gallstone obstructing the biliary tree or adhesions externally compressing the small bowel. There appears to be subsets of mechanosensitive receptors differentiated in their location and sensitivity. Mechanoreceptors in the mucosa and serosa primarily respond to blunt probing, whereas mechanoreceptors in smooth muscle primarily respond to circumferential stretching.¹¹ In addition, nerve endings associated with intramural blood vessels are also stimulated by stretch and distention of the hollow viscera.¹² From in vivo studies, both low-threshold and high-threshold mechanosensitive afferent fibers have been characterized. Low-threshold afferents account for the majority (75%-80%) of the studied samples and are activated by low distending pressures (<5 mm Hg) but are capable of sensing in the noxious range (25-30 mm Hg). High-threshold afferents account for the minority (20%-25%) and are only activated by pain-eliciting pressures above 25-30 mm Hg. Thus, low-threshold afferents likely encode normal physiological sensations (ie, satiety), whereas high-threshold afferents give rise to acute pathological conditions.

Mechanoreceptors and chemoreceptors likely overlap in the nerve endings of A-δ and C afferent fibers. It has been demonstrated in animal studies that mechanosensitive afferents not only respond to but are sensitized by chemical and thermal insults such as in the setting of inflammation. However, not all afferents are inherently capable of mechanoreception. Termed mechanically insensitive afferents (MIAs), these make up 25% of innervation of the mouse colon.¹³ They can, interestingly, acquire temporary mechanosensitivity after exposure to inflammatory mediators. This suggests an integral role of both inherently mechanosensitive afferents and MIAs in propagating and maintaining pain in the inflammatory process.

The differential diagnosis of acute abdominal pain is broad, and evaluation should begin with the patient’s history. The initial location of pain informs on the possible organ involved based simply on anatomy. The onset, duration, severity, quality of pain, as well as exacerbating and remitting factors further narrow the diagnosis. Associated symptoms can give important clues, such as constipation with small bowel obstruction or jaundice with cholestatic conditions. A thorough interrogation of past medical history, for example, heavy alcohol use or previous abdominal surgeries, is also helpful. Symptoms that may signal impending clinical deterioration include high fever, protracted vomiting, syncope, and sudden change in pain severity.

A physical examination should first focus on vital signs and general appearance to quickly determine the acuity of abdominal pain. Tachycardia and hypotension suggest a state of shock; both hypovolemic and distributive shock can be seen in GI emergencies. Determining the
presence or absence of classic peritoneal signs (guarding, rigidity, rebound tenderness) is also a priority. Once deemed clinically stable, examine the area of pain with inspection, percussion, palpation, and auscultation.

The need for lab tests should be guided by the history and physical examination. Practically, however, especially for toxic-appearing patients arriving in the emergency department, a broad panel of blood work is typically sent. A basic metabolic panel evaluates electrolyte derangements and renal function in the setting of GI losses and hypovolemia. A complete blood count identifies leukocytosis and bandemia in support for ongoing infection. Liver function tests are important for hepatobiliary etiologies, while amylase and lipase help diagnose pancreatitis. Urinalysis, urine culture, and pregnancy test are typically obtained to rule out genitourinary and gynecological causes.