When Aristotle described the five senses, he omitted the sensation of pain. The ancient Greeks considered pain to be an emotion or something unpleasant, the opposite of pleasure. For centuries, arguments have raged over whether pain is a separate, distinct sensation or a psychological reaction to a complex feeling. Even though perception of pain now is assigned to a specific sensory faculty, the chronic recurrent abdominal pain of childhood, more than any other form of pain, exemplifies this historical uncertainty.

Receptors for transmitting pain are described morphologically as undifferentiated nerve endings. They can be stimulated by mechanical, chemical, or thermal stimuli. In the case of the viscera, these receptors are most sensitive to mechanical stimuli. Receptor substance is contained within vesicles at the nerve ending and is released on stimulation, thus causing depolarization of the nerve when it combines with receptors on the external surface. This action is terminated by a specific hydrolytic enzyme surrounding the nerve terminal. If severe trauma to tissue occurs, this hydrolytic enzyme may be destroyed, resulting in prolonged depolarization of the nerve cells by the receptor substance and persistent pain. One of the receptor substances thought to be active in pain fibers is substance P, an 11-amino acid peptide, but other substances also have been identified.

The afferent nerve fibers involved in the transmission of pain follow a course through the sympathetic ganglion chain and enter the dorsal horn of the spinal cord, where they synapse. Afferents from the viscera enter the dorsal horn along with afferents from cutaneous structures of the corresponding dermatome. These two sources of nerve impulses overlap at the synaptic junctions and give rise to the phenomenon of referred pain. As the input from visceral structures increases, more impulses are received by the fibers, which share their input between visceral and cutaneous structures. This input eventually is perceived by the brain as arising from cutaneous structures.

Another mechanism that may play a role in the cutaneous localization of visceral pain is the peritoneocutaneous reflex of Morley. Certain somatic nerve endings in the parietal peritoneum may extend into the roots of the mesentery and posterior portion of the diaphragm. When these nerves are stimulated, pain is referred to the corresponding skin area. This reflex usually is the result of inflammation from peritonitis.

Neurons that synapse with afferents from the viscera in the dorsal horn of the spinal cord cross to the opposite side and ascend through the lateral spinothalamic tract to the thalamus. A third neuron then carries the sensation by means of the internal capsule to the cerebral cortex.

A satisfactory theory of pain must account for the evidence that local factors in the spinal cord, and events occurring in the cerebral cortex (e.g., anxiety) may influence the perception or threshold of pain. The gate theory is an attempt to explain this phenomenon. It proposes that pain fibers are subject to the influence of larger-diameter afferents that originate in the substantia gelatinosa of the spinal cord. These neurons interact through an axoaxonic synapse that, under normal conditions, is dominant, and the gate is closed. As excitation from the viscera increases, this modulating effect is overcome, and pain is felt. Feedback from the brain may alter the transmission from this interneuron. In functional abdominal pain, anxiety may decrease the modulating effect to the point that normal intestinal sensations are perceived as pain. The interneuronal receptors in the system are opiate receptors that normally are activated by the endogenously produced opiates, enkephalins, and endorphins.