Referred pain
Encyclopedia
Referred pain is pain
perceived at a location other than the site of the painful stimulus. An example is the case of ischemia
brought on by a myocardial infarction
(heart attack), where pain is often felt in the neck, shoulders, and back rather than in the chest, the site of the injury. The International Association for the Study of Pain
, as of 2001, has not officially defined the term; hence several authors have defined the term differently.
Radiation(pain) is different from referred pain.The pain related to a myocardial infarction could either be referred pain or pain radiating from the chest. Classically the pain associated with a myocardial infarction is located in the mid or L sided 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. Referred pain is when the pain is located away from or adjacent to the organ involved. Referred pain would be when a person has pain only in their jaw or left arm, but not in the chest. Myocardial infarction can rarely present as referred pain and this usually occurs in people with diabetes or older age.
Physician
s and scientists have known about referred pain since the late 1880s. Despite an increasing amount of literature on the subject, the mechanism
of referred pain is unknown, although there are several theories.
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). 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.
Criticism of this model arises from its inability to explain why there is a delay between the onset of referred pain after local pain stimulation. Experimental evidence also shows that referred pain is often unidirectional. For example stimulated local pain in the anterior tibial muscle causes referred pain in the ventral portion of the ankle; however referred pain moving in the opposite direction has not been shown experimentally. Lastly, the threshold for the local pain stimulation and the referred pain stimulation are different, but according to this model they should both be the same.
created what he termed "an irritable focus". This focus caused some stimuli to be perceived as referred pain. However, the theory did not gain widespread acceptance from critics due to its dismissal of visceral pain.
Recently this simple idea has regained some credibility under a new term, central sensitization. This theory, therefore, explains why changes in somatosensory sensibility could be undergoing processes similar to the dorsal horn and the brainstem. Additionally, the delay in appearance of referred pain shown in laboratory experiments can be explained due to the time required to create the central sensitization.
Several characteristics are in line with this theory of referred pain such as dependency on stimulus and the time delay in the appearance of referred pain as compared to local pain. However, the appearance of new receptive fields, which is interpreted to be referred pain, conflicts with the majority of experimental evidence from studies including studies of healthy individuals. Furthermore, referred pain generally appears within seconds in humans as opposed to minutes in animal models. Some scientists attribute this to a mechanism or influence downstream in the supraspinal pathways. Neuroimaging techniques such as PET
scans or fMRI may visualize the underlying neural processing pathways responsible in future testing.
, 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.
Studies have reported that the majority of patients that centralized were able to avoid spinal surgery via isolating the area of local pain. However, the patients that did not centralize had to undergo surgery to diagnose and correct problems. As a result of this study there has been a lot of research into the elimination of referred pain through certain body movements.
One example of this is referred pain in the calf. McKenzie showed that the referred pain would move closer to the spine when the patient bent backwards in full extension a few times. More importantly, the referred pain would dissipate even after the movements were stopped.
Further, recent research has found that ketamine
, a sedative, is capable of blocking referred pain. The study was conducted on patients suffering from 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 it does in normal people. 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.
Pain
Pain is an unpleasant sensation often caused by intense or damaging stimuli such as stubbing a toe, burning a finger, putting iodine on a cut, and bumping the "funny bone."...
perceived at a location other than the site of the painful stimulus. An example is the case of ischemia
Ischemia
In medicine, ischemia is a restriction in blood supply, generally due to factors in the blood vessels, with resultant damage or dysfunction of tissue. It may also be spelled ischaemia or ischæmia...
brought on by a myocardial infarction
Myocardial infarction
Myocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...
(heart attack), where pain is often felt in the neck, shoulders, and back rather than in the chest, the site of the injury. The International Association for the Study of Pain
International Association for the Study of Pain
The International Association for the Study of Pain is an international professional organization promoting research, education and policies for the knowledge and management of pain. The IASP was founded in 1973, following the Seattle-Issaquah conference, under the leadership of John Bonica. Its...
, as of 2001, has not officially defined the term; hence several authors have defined the term differently.
Radiation(pain) is different from referred pain.The pain related to a myocardial infarction could either be referred pain or pain radiating from the chest. Classically the pain associated with a myocardial infarction is located in the mid or L sided 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. Referred pain is when the pain is located away from or adjacent to the organ involved. Referred pain would be when a person has pain only in their jaw or left arm, but not in the chest. Myocardial infarction can rarely present as referred pain and this usually occurs in people with diabetes or older age.
Physician
Physician
A physician is a health care provider who practices the profession of medicine, which is concerned with promoting, maintaining or restoring human health through the study, diagnosis, and treatment of disease, injury and other physical and mental impairments...
s and scientists have known about referred pain since the late 1880s. Despite an increasing amount of literature on the subject, the mechanism
Mechanism (biology)
In biology --and in science in general-- a mechanism is a complex object or, more generally, a process that produces a regular phenomenon. For example, natural selection is one of the mechanisms of biological evolution, other being genetic drift, biased mutation, and gene flow; competition,...
of referred pain is unknown, although there are several theories.
Characteristics
- The size of referred pain is related to the intensity and duration of ongoing/evoked pain.
- Temporal summation is a potent mechanism for generation of referred muscle pain.
- Central hyperexcitability is important for the extent of referred pain.
- Patients with chronic musculoskeletal pains have enlarged referred pain areas to experimental stimuli. The proximal spread of referred muscle pain is seen in patients with chronic musculoskeletal pain and very seldom is it seen in healthy individuals.
- Modality-specific somatosensory changes occur in referred areas, which emphasize the importance of using a multimodal sensory test regime for assessment.
Mechanism
There are several proposed mechanisms for referred pain. Currently there is no definitive consensus regarding which theory may be 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). 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.
Convergent-projection
This represents one of the earliest theories on the subject of referred pain. It is based on the work of W.A. Sturge and J. Ross from 1888 and later TC Ruch in 1961. This theory proposes that afferent nerve fibers from tissues converge onto the same spinal neuron. This theory explains why referred pain is believed to be segmented in much the same way as the spinal cord. Additionally, experimental evidence shows that when local pain (pain at the site of stimulation) is intensified the referred pain is intensified as well.Criticism of this model arises from its inability to explain why there is a delay between the onset of referred pain after local pain stimulation. Experimental evidence also shows that referred pain is often unidirectional. For example stimulated local pain in the anterior tibial muscle causes referred pain in the ventral portion of the ankle; however referred pain moving in the opposite direction has not been shown experimentally. Lastly, the threshold for the local pain stimulation and the referred pain stimulation are different, but according to this model they should both be the same.
Convergence-facilitation
In 1893 J MacKenzie created an alternate theory based on the ideas of Sturge and Ross. He believed that the internal organs were insensitive to stimuli. Furthermore, he believed that nonnociceptive afferent inputs to the spinal cordSpinal cord
The spinal cord is a long, thin, tubular bundle of nervous tissue and support cells that extends from the brain . The brain and spinal cord together make up the central nervous system...
created what he termed "an irritable focus". This focus caused some stimuli to be perceived as referred pain. However, the theory did not gain widespread acceptance from critics due to its dismissal of visceral pain.
Recently this simple idea has regained some credibility under a new term, central sensitization. This theory, therefore, explains why changes in somatosensory sensibility could be undergoing processes similar to the dorsal horn and the brainstem. Additionally, the delay in appearance of referred pain shown in laboratory experiments can be explained due to the time required to create the central sensitization.
Axon-reflex
This theory suggests that the afferent fiber is bifurcated before connecting to the dorsal horn. Bifurcated fibers do exist in muscle, skin, and intervertebral discs. Yet these particular neurons are rare and are not representative of the whole body. Axon-Reflex also does not explain the time delay before the appearance of referred pain, threshold differences for stimulating local and referred pain, and somatosensory sensibility changes in the area of referred pain.Hyperexcitability
This theory hypothesizes that referred pain has no central mechanism. However, it does say that there is one central characteristic that predominates. This theory is derived from experiments involving noxious stimuli and recordings from the dorsal horn of animals. Experiments revealed that referred pain sensations began minutes after muscle stimulation. Pain was felt in a receptive field that was some distance away from the original receptive field. According to the theory new receptive fields are created as a result of the opening of latent convergent afferent fibers in the dorsal horn. This signal could then be perceived as referred pain.Several characteristics are in line with this theory of referred pain such as dependency on stimulus and the time delay in the appearance of referred pain as compared to local pain. However, the appearance of new receptive fields, which is interpreted to be referred pain, conflicts with the majority of experimental evidence from studies including studies of healthy individuals. Furthermore, referred pain generally appears within seconds in humans as opposed to minutes in animal models. Some scientists attribute this to a mechanism or influence downstream in the supraspinal pathways. Neuroimaging techniques such as PET
Positron emission tomography
Positron emission tomography is nuclear medicine imaging technique that produces a three-dimensional image or picture of functional processes in the body. The system detects pairs of gamma rays emitted indirectly by a positron-emitting radionuclide , which is introduced into the body on a...
scans or fMRI may visualize the underlying neural processing pathways responsible in future testing.
Thalamic-convergence
This theory suggests that referred pain is perceived as such due to the summation of neural inputs in the brain, as opposed to the spinal cord, from the injured area and the referred area. Experimental evidence on this theory is lacking. However, pain studies performed on monkeys revealed several pathways converging on both subcortical and cortical neurons.Examples
| Location | Description |
|---|---|
| Upper chest/left limb | Myocardial ischaemia (the loss of blood flow to a part of the heart muscle tissue) is possibly the best known example of referred pain; the sensation can occur in the upper chest as a restricted feeling, or as an ache in the left shoulder, arm or even hand. |
| Head | “Ice-cream headache” or “brain freeze” is another example of referred pain, in which the vagus nerve Vagus nerve The vagus nerve , also called pneumogastric nerve or cranial nerve X, is the tenth of twelve paired cranial nerves... or the trigeminal nerve Trigeminal nerve The trigeminal nerve contains both sensory and motor fibres. It is responsible for sensation in the face and certain motor functions such as biting, chewing, and swallowing. Sensory information from the face and body is processed by parallel pathways in the central nervous system... in the throat and the palate, respectively, transmit pain signals, because of the rapid cooling and rewarming of the capillaries in the sinuses. |
| General | Phantom limb pain, a type of referred pain, is the sensation of pain from a limb that has been lost or from which a person no longer receives physical signals. It is an experience almost universally reported by amputees and quadriplegics. |
| Right Tip of scapula. | Liver Liver The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion... , gallbladder Gallbladder In vertebrates the gallbladder is a small organ that aids mainly in fat digestion and concentrates bile produced by the liver. In humans the loss of the gallbladder is usually easily tolerated.... |
| Left shoulder | Thoracic diaphragm Thoracic diaphragm In the anatomy of mammals, the thoracic diaphragm, or simply the diaphragm , is a sheet of internal skeletal muscle that extends across the bottom of the rib cage. The diaphragm separates the thoracic cavity from the abdominal cavity and performs an important function in respiration... (Kehr's sign Kehr's sign Kehr's sign is the occurrence of acute pain in the tip of the shoulder due to the presence of blood or other irritants in the peritoneal cavity when a person is lying down and the legs are elevated. Kehr's sign in the left shoulder is considered a classical symptom of a ruptured spleen... ), lung Lung The lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart... |
Laboratory testing methods
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.Algogenic substances
In recent years several different chemicals have been used to induce referred pain including bradykinin, substance PSubstance P
In the field of neuroscience, substance P is a neuropeptide: an undecapeptide that functions as a neurotransmitter and as a neuromodulator. It belongs to the tachykinin neuropeptide family. Substance P and its closely related neuropeptide neurokinin A are produced from a polyprotein precursor...
, capsaicin
Capsaicin
Capsaicin 2CHCH=CH4CONHCH2C6H3-4--3- ) is the active component of chili peppers, which are plants belonging to the genus Capsicum. It is an irritant for mammals, including humans, and produces a sensation of burning in any tissue with which it comes into contact...
, and serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
. However before any of these substances became widespread in their use a solution of hypertonic saline
Saline (medicine)
In medicine, saline is a general term referring to a sterile solution of sodium chloride in water but is only sterile when it is to be placed intravenously, otherwise, a saline solution is a salt water solution...
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 electrical stimulation
Intramuscular electrical stimulation (IMES) of muscle tissue has been used in various experimental and clinical settings. The advantage to using an IMES system over a standard such as hypertonic saline is that IMES can be turned on and off. This allows the researcher to exert a much higher degree of control and precision in terms of the stimulus and the measurement of the response. The method is easier to carry out than the injection method as it does not require special training in how it should be used. The frequency of the electrical pulse can also be controlled. For most studies a frequency of about 10 Hz is needed to stimulate both local and referred pain.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.
Use in clinical diagnosis and treatments
Referred pain can be indicative of nerve damage. A case study done on a 63 year old man with a sustained injury during his childhood developed referred pain symptoms after his face or back was touched. After even a light touch, there was shooting pain in his arm. The study concluded that the reason for this man's pain was possibly due to a neural reorganization which sensitized regions of his face and back after the nerve damage occurred. It is mentioned that this case is very similar to what phantom limb syndrome patients suffer. This conclusion was based on experimental evidence gathered by V. Ramachandran in 1993, with the difference being that the arm that is in pain is still attached to the body.Orthopedic diagnosis
From the above examples one can see why understanding of referred pain can lead to better diagnoses of various conditions and diseases. In 1981 physiotherapist Robin McKenzie described what he termed centralization. He concluded that centralization occurs when referred pain moves from a distal to a more proximal location. Observations in support of this idea were seen when patients would bend backward and forward during an examination.Studies have reported that the majority of patients that centralized were able to avoid spinal surgery via isolating the area of local pain. However, the patients that did not centralize had to undergo surgery to diagnose and correct problems. As a result of this study there has been a lot of research into the elimination of referred pain through certain body movements.
One example of this is referred pain in the calf. McKenzie showed that the referred pain would move closer to the spine when the patient bent backwards in full extension a few times. More importantly, the referred pain would dissipate even after the movements were stopped.
General diagnosis
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
Ketamine
Ketamine is a drug used in human and veterinary medicine. Its hydrochloride salt is sold as Ketanest, Ketaset, and Ketalar. Pharmacologically, ketamine is classified as an NMDA receptor antagonist...
, a sedative, is capable of blocking referred pain. The study was conducted on patients suffering from fibromyalgia
Fibromyalgia
Fibromyalgia is a medical disorder characterized by chronic widespread pain and allodynia, a heightened and painful response to pressure. It is an example of a diagnosis of exclusion...
, 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 it does in normal people. 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.