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Pain perceived at a location other than the site of the painful stimulus

Referred pain, also called reflective pain, is pain perceived at a location other than the site of the painful stimulus. An example is the case of angina pectoris brought on by a myocardial infarction (heart attack), where pain is often felt in the left side of neck, left shoulder, and back rather than in the thorax (chest), the site of the injury. The International Association for the Study of Pain has not officially defined the term; hence, several authors have defined it differently. Referred pain has been described since the late 1880s. Despite an increasing amount of literature on the subject, the biological mechanism of referred pain is unknown, although there are several hypotheses. Radiating pain is slightly different from referred pain; for example, the pain related to a myocardial infarction could either be referred or radiating pain from the chest. Referred pain is when the pain is located away from or adjacent to the organ involved; for instance, when a person has pain only in their jaw or left arm, but not in the chest. Radiating pain would have an origin, where the patient can perceive pain, but the pain also spreads ("radiates") out from this origin point to cause the pain to be perceived in a wider area in addition.

The size of referred pain is related to the intensity and duration of ongoing/evoked pain.

There are several proposed mechanisms for referred pain. Currently there is no definitive consensus regarding which is correct. The cardiac general visceral sensory pain fibers follow the sympathetics back to the spinal cord and have their cell bodies located in thoracic dorsal root ganglia 1 4(5). As a general rule, in the thorax and abdomen, general visceral afferent (GVA) pain fibers follow sympathetic fibers back to the same spinal cord segments that gave rise to the preganglionic sympathetic fibers. The central nervous system (CNS) perceives pain from the heart as coming from the somatic portion of the body supplied by the thoracic spinal cord segments 1 4(5). Classically the pain associated with a myocardial infarction is located in the mid or left side of the chest where the heart is actually located. The pain can radiate to the left side of the jaw and into the left arm. Myocardial infarction can rarely present as referred pain and this usually occurs in people with diabetes or older age. Also, the dermatomes of this region of the body wall and upper limb have their neuronal cell bodies in the same dorsal root ganglia (T1 5) and synapse in the same second order neurons in the spinal cord segments (T1 5) as the general visceral sensory fibers from the heart. The CNS does not clearly discern whether the pain is coming from the body wall or from the viscera, but it perceives the pain as coming from somewhere on the body wall, i. e. substernal pain, left arm/hand pain, jaw pain.

Pain is studied in a laboratory setting due to the greater amount of control that can be exerted. For example, the modality, intensity, and timing of painful stimuli can be controlled with much more precision. Within this setting there are two main ways that referred pain is studied.

In recent years several different chemicals have been used to induce referred pain including bradykinin, substance P, capsaicin, and serotonin. However, before any of these substances became widespread in their use a solution of hypertonic saline was used instead. Through various experiments it was determined that there were multiple factors that correlated with saline administration such as infusion rate, saline concentration, pressure, and amount of saline used. The mechanism by which the saline induces a local and referred pain pair is unknown. Some researchers have commented that it could be due to osmotic differences, however that is not verified. Using this method it has been observed that significantly higher stimulus strength is needed to obtain referred pain relative to the local pain. There is also a strong correlation between the stimulus intensity and the intensity of referred and local pain. It is also believed that this method causes a larger recruitment of nociceptor units resulting in a spatial summation. This spatial summation results in a much larger barrage of signals to the dorsal horn and brainstem neurons.

As with myocardial ischaemia, referred pain in a certain portion of the body can lead to a diagnosis of the correct local center. Somatic mapping of referred pain and the corresponding local centers has led to various topographic maps being produced to aid in pinpointing the location of pain based on the referred areas. For example, local pain stimulated in the esophagus is capable of producing referred pain in the upper abdomen, the oblique muscles, and the throat. Local pain in the prostate can radiate referred pain to the abdomen, lower back, and calf muscles. Kidney stones can cause visceral pain in the ureter as the stone is slowly passed into the excretory system. This can cause immense referred pain in the lower abdominal wall. Further, recent research has found that ketamine, a sedative, is capable of blocking referred pain. The study was conducted on patients with fibromyalgia, a disease characterized by joint and muscle pain and fatigue. These patients were looked at specifically due to their increased sensitivity to nociceptive stimuli. Furthermore, referred pain appears in a different pattern in fibromyalgic patients than non fibromyalgic patients. Often this difference manifests as a difference in terms of the area that the referred pain is found (distal vs. proximal) as compared to the local pain. The area is also much more exaggerated owing to the increased sensitivity.