Early ReportContribution of central sensitisation to the development of noncardiac chest pain
Introduction
Angina pectoris generally indicates myocardial ischaemia and is characterised by pain within the centre of the chest, which radiates to the neck and upper limbs and can be associated with tenderness of the anterior chest wall.1 However, in up to a third of patients, no cardiac cause is found, and these patients are labelled as having noncardiac chest pain.2 In most of these patients the pain is attributed to the oesophagus on clinical grounds,3, 4 but conventional investigations do not identify the cause of the pain.
Research studies of non-cardiac chest pain have suggested that visceral pain hypersensitivity may be important in its pathogenesis, largely because stimulation of the oesophagus induces pain at intensities that are innocuous in healthy people.5 The neurophysiological basis for this hypersensitivity is unclear; proposed mechanisms include abnormally heightened afferent nerve responses to normal sensory inputs and abnormal cognitive processing of such inputs.2
Somatic pain hypersensitivity after tissue injury typically has two important properties. First, it manifests both as allodynia (a previously innocuous stimulus induces pain) and hyperalgesia (the pain response to a noxious stimulus is exaggerated). Second, it is diffuse, present not only at the site of injury (primary), but also in surrounding healthy tissue (secondary).6, 7 Primary allodynia or hyperalgesia is the result of an inflammatorymediator-induced increase in the transduction sensitivity of the peripheral terminals of high-threshold nociceptive fibres.6, 7 Secondary allodynia or hyperalgesia results solely from an increase in excitability of spinal-cord neurons (central sensitisation) induced by activation of nociceptive C-fibres in the area of injury.6, 7, 8 Central sensitisation is mediated by phosphorylation of N-methyl-D-aspartate (NMDA) receptors expressed by dorsal-horn neurons,6, 7, 8, 9 which leads to an increase in their excitability and receptive field size. This process results in the recruitment and amplification of both non-nociceptive and nociceptive inputs from adjacent healthy tissue, thereby generating secondary allodynia and hyperalgesia, respectively.
Despite supporting data from studies in animals,10, 11, 12 a role for central sensitisation in visceral pain hypersensitivity has not been established in human beings. We have explored whether secondary allodynia can be induced within the human oesophagus and whether central sensitisation has a role in the pathogenesis of visceral hypersensitivity in non-cardiac chest pain.
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Participants
We recruited 19 healthy volunteers (18 male, one female; aged 21–39 years [mean 28]) affiliated with the gastrointestinal unit at Hope Hospital, Salford, UK. None had a history of chest pain or oesophageal symptoms and none were taking any prescribed medication. All had normal oesophageal motor function on standard intraluminal manometric testing. Six (all male, aged 21–38 years) were used as controls for the patients with non-cardiac chest pain.
Seven patients with non-cardiac chest pain (five
Results
The words most commonly chosen by healthy volunteers to describe pain elicited by electrical stimulation of the upper oesophagus were pulsing, sharp, and throbbing, and the pain was referred to the lower throat. In the lower oesophagus, the words chosen were burning and dull, and the pain was referred to the lower chest.
In the patients with non-cardiac chest pain, the effects of stimulation of the upper oesophagus were described as pulsing, sharp, throbbing, tight, and stabbing, also with
Discussion
We found that acid infusion to the lower oesophagus induced a decrease in pain threshold within both the upper oesophagus and the anterior chest wall. This concurrent visceral and somatic pain hypersensitivity, well outside the area of acid exposure, must be due to a change in sensory processing within the central nervous system; central sensitisation is the most plausible explanation. Central sensitisation could be a result of the C-fibre sensory input from the lower oesophagus, activated
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