Somatic Pain

Somatic structures, such as the skin, are invested with a wide variety of nociceptors, each with selective sensitivities to mechanical, thermal, or chemical stimuli, in addition to the polymodal nociceptor that responds to multiple modalities of noxious stimuli. Cutaneous nociceptors are characterized by very infrequent or no spontaneous discharges, an ability to encode stimulus intensities in the noxious (but not innocuous) range, and most importantly, sensitization. Sensitization refers to an increase in the magnitude of response after tissue insult, sometimes associated with an increase in spontaneous activity as well as a de­­crease in response threshold. This attribute of nociceptors contributes to development of hyperalgesia, or an increased response to a stimulus that is normally painful.

When a tissue is injured, a host of sensitizing chemicals are synthesized at the site of injury or released from circulating cells that are attracted to the site of injury. These include amines (e.g., histamine and serotonin), peptides (e.g., substance P and calcitonin gene—related peptide), kinins (e.g., bradykinin), neurotrophins, cytokines, prostaglandins, leukotrienes, excitatory amino acids (e.g., glutamate), and free radicals. However, it is unlikely that any one putative chemical mediator is responsible for nociceptor sensitization. Although substance P, for example, is contained in most nociceptor cell bodies, it is also present in a significant number of non-nociceptor cell bodies. Similarly, other neuropeptides, such as calcitonin gene—related peptide, somatostatin, and galanin, are found more commonly in small- to intermediate-sized dorsal root ganglion cell bodies.

Visceral Pain

Input to the central nervous system from aortic baroreceptors, gastric chemoreceptors, and pulmonary stretch receptors is rarely perceived. Nevertheless, it is evident that visceral afferents possess many of the characteristics of nociceptors.

All viscera possess a dual innervation. Organs of the thoracic cavity are innervated by vagal afferent fibers with cell bodies in the nodose and jugular ganglia as well as by spinal afferent fibers with cell bodies in thoracic dorsal root ganglia. Unlike their somatic counterpart, spinal visceral afferent fibers typically traverse either or both prevertebral and paravertebral ganglia en route to the spinal cord. Thus, in contrast to somatic input to the central nervous system, which has a single, usually spinal, destination, input to the central nervous system from organs in the thoracic cavity arrives at two locations, namely the brain-stem nucleus tractus solitarii (vagal afferent input) and the thoracic spinal cord. Accordingly, the potential exists for interaction in the central nervous system of inputs from the same thoracic organ. The esophagus and heart also possess an intrinsic nervous system with cell bodies in the organ wall or in ganglia in the epicardial fat.

Further differences between somatic and visceral innervation relate to the density of innervation and spinal pattern of termination. In general, the number of visceral afferent fibers is disproportionately less than the number of somatic afferent fibers, although the rostrocaudal spread of visceral afferent fiber terminals in the spinal cord is considerably greater than the spread of central terminals from somatic afferent fibers. Although this means that there are fewer central visceral terminals in the spinal cord, visceral afferent fiber terminals have many more terminal swellings (suggestive of synapses) than somatic nociceptor terminals and they spread over several spinal cord segments. The obvious consequence of the low number of visceral afferents and greater intraspinal spread is loss of spatial discrimination, consistent with the diffuse, difficult-to-localize, nature of visceral pain.

The axons of visceral sensory neurons are, with rare exception, either thin, myelinated Αδ fibers or unmyelinated C fibers. In general, Αδ fibers, having some myelin, carry moderately fast impulses, usually of acute or sharp pain but also temperature. C fibers, without myelin, carry slow impulses, usually of burning pain. Generally the proportion of Αδ fibers in visceral sensory nerves is less than the proportion of C fibers. In addition, Αδ fibers are fibers with a low threshold for response to mechanical stimulation, whereas C fibers have high thresholds; however, this is not universal.

Unlike tissue-damaging stimuli that produce pain in somatic structures, tissue injury is not required for production of pain in the viscera. For the lower airways, irritants contained in smoke, ammonia, and other inhaled substances are capable of producing discomfort and pain. For the heart and mesentery, ischemia can be an adequate stimulus. For hollow organs of the gastrointestinal tract, distention of the lumen of the organ, which activates stretch and tension receptors in the smooth muscles, is typically adequate.

Hollow viscera, including the esophagus, are innervated by two populations of mechanosensitive afferent fibers, namely a larger group (70% to 80%) of fibers that have low thresholds for response (i.e., within the physiologic range), and a smaller group (20% to 30%) of fibers that have thresholds for response that fall in the noxious range. All mechanosensitive visceral afferent fibers may function in some circumstances as nociceptors, and low- and high-threshold mechanosensitive fibers contribute to discomfort and pain that arise from the viscera.

Silent nociceptors, a relatively new category of receptor/afferent fibers, may also contribute to altered sensations from visceral structures. Silent nociceptors, more appropriately termed “mechanically insensitive afferents” have no spontaneous activity and do not respond to acute, high-intensity mechanical stimulation in normal circumstances. After tissue insult, mechanically insensitive afferents typically begin to discharge spontaneously and acquire sensitivity to mechanical stimulation. However, the contribution of such “silent” or “sleeping” afferent fibers to altered sensations that arise from the viscera is uncertain at present.

Pleuropulmonary Disorders

Although the lung parenchyma and visceral pleura are considered to be insensitive to ordinary noxious stimuli, immunohistochemical studies from vagal denervation and talc-pleurodesis animal models indicate the presence of nerve fibers in the visceral pleura that may be capable of conducting pain stimuli. Pain does arise from stimulation of the mucosa of the trachea and main bronchi. The lungs and bronchi are innervated with mechanoreceptors that respond to stretch (inflation or deflation of the lungs) as well as chemoreceptors called J receptors that respond to a variety of pain-inducing chemicals, including bradykinin, prostaglandins, serotonin, and capsaicin. Inhalation of irritant substances, such as ammonia, can trigger a cough reflex and can produce a sense of rawness, tightness in the chest, and pain. In addition, rapidly adapting mechanoreceptors that respond to lung deflation are also “irritant receptors” and signal respiratory pain. J receptors have been proposed to contribute to discomfort and pain that accompanies breathlessness.

These receptors are, in turn, innervated by vagal and spinal splanchnic afferent fibers. Nerve fibers that travel in the vagus nerves, including myelinated axons that carry impulses from slowly adapting stretch receptors in the conducting airways, myelinated axons that lead from rapidly adapting irritant cough receptors in the trachea and bronchi, and unmyelinated axons that subserve the extensive network of C fiber receptors (e.g., “pulmonary” J receptors and “bronchial” C fibers), are most important.

The pulmonary causes of chest pain may be related to the pleural tissue, pulmonary vessels, or lung parenchyma. Causes of chest pain related to the lung parenchyma include infection, cancer, or chronic diseases such as sarcoidosis. These are discussed in more detail elsewhere in the textbook.

Tracheobronchitis

Pain of tracheal origin is generally felt in the midline, anteriorly, from the larynx to the xyphoid. Conversely, pain from either main bronchus is felt in the ipsilateral anterior chest near the sternum or in the anterior neck near the midline. Whatever its origin, pain related to tracheobronchitis is typically described as “raw” or “burning” but may be “dull” or “achy,” and exaggerated by deep breathing. This type of discomfort usually denotes the presence of viral or bacterial tracheobronchitis or, less often, a malignancy but can also be experienced during exposure to noxious gases. Tracheobronchial pain is thought to be mediated by bronchial C fibers. Experimentally induced tracheal pain can be abolished by vagal blockade or by vagotomy.

Inflammation or Trauma of the Chest Wall (see Chapter 98 )

Inflammation of, or trauma to, the joints, muscles, cartilages, bones, and fasciae that constitute the thoracic cage can cause chest pain. Fibromyalgia, fibrositis, and other rheumatologic disorders of the thoracic cage, such as ankylosing spondylitis, are known to cause pain and discomfort in the chest. Acute or chronic inflammation of the xiphoid process (xiphodynia) and superficial thrombophlebitis of the chest wall (Mondor syndrome) may also be uncommon sources of chest pain. Occasionally pain related to respiration may be experienced along the costal margins after vigorous exercise. In addition, metastatic malignancy may present as painful lesions of the chest wall, sometimes with spontaneous rib fractures. Another confusing source of chest pain is infectious arthritis of the sternoclavicular joint or costochondral junctions, which is an increasing problem among injection drug users.

With costochondritis, chest wall pain arises from the costochondral cartilaginous junctions. It is usually described as “dull with a gnawing, aching quality.” There is little, if any, relationship to respiratory or other body movements. Tenderness to palpation is clearly localized to one or more of the costal cartilages. There may be redness, swelling, and enlargement of the costal cartilages (Tietze syndrome). The most common sites of costosternal perichondritis are the second, third, and fourth cartilages, but any part of the large cartilaginous shield along the central and lower portions of the anterior thoracic cage may be involved.

The pain of intercostal neuritis or radiculitis, which often originates from disorders of the cervicodorsal spine or nerve roots, is usually perceived in the rib cage. The superficial, spontaneous lancinating or electric shock–like pain of intercostal neuritis is typically felt over the cutaneous distribution of the involved nerves and may be worsened by taking deep breaths, coughing, and sneezing. Unlike pleurisy, neuritic pain is usually not aggravated by ordinary breathing; the diagnosis is supported by the presence of hyperalgesia or anesthesia on examination of the skin. In some patients with neuritis/radiculitis, the diagnosis becomes evident 2 or 3 days later with the development of the characteristic vesicular rash of herpes zoster over the involved dermatome. Painful radiculitis is also recognized as an important early manifestation of Lyme disease.

Injuries to the ribs (fracture) and thoracic cage muscles (strain, tears, or hematoma) are common causes of localized chest pain. The relationship of the pain to trauma is obvious in most instances, but diagnosis may be elusive, particularly if the inciting event is relatively minor (e.g., unnoticed episode of coughing) or when the onset of pain is delayed.

Cardiovascular Disorders

Mechanosensitive and chemosensitive afferent fibers are present in the myocardium. Chemical stimuli are believed to be the most important causes of cardiac pain, but mechanical distention or distortion may also play a role. Sensory fibers travel from the heart to the spinal cord through the several cardiac nerves, the upper five thoracic sympathetic ganglia, and finally, the upper five thoracic dorsal roots; afferent fibers also reach the brain through the vagus nerves. Cardiac pain is likely associated with activity in afferent fibers contained in the spinal afferent innervation of the heart.