Elsevier

The Lancet

Volume 356, Issue 9236, 30 September 2000, Pages 1154-1159
The Lancet

Early Report
Contribution of central sensitisation to the development of noncardiac chest pain

https://doi.org/10.1016/S0140-6736(00)02758-6Get rights and content

Summary

Background

Non-cardiac chest pain mimics angina pectoris but generally originates from the oesophagus. Visceral hypersensitivity may contribute, but its neurophysiological basis is unclear. We investigated whether central sensitisation, an activity-dependent amplification of sensory transfer in the central nervous system, underlies visceral pain hypersensitivity and non-cardiac chest pain.

Methods

We studied 19 healthy volunteers and seven patients with non-cardiac chest pain. Acid was infused into the lower oesophagus. Sensory responses to electrical stimulation were monitored within the acid-exposed lower oesophagus, the non-exposed upper oesophagus, and the cutaneous area of pain referral, before and after the infusion.

Findings

In healthy volunteers, acid infusion into the lower oesophagus lowered the pain threshold in the upper oesophagus (mean decrease 18·2% [95% Cl 10·4 to 26·0]; p=0·01) and on the chest wall (24·5% [10·2 to 38·7]; p=0·01). Patients with non-cardiac chest pain had a lower resting oesophageal pain threshold than healthy controls (45 [30 to 58] vs 64 [49 to 81] mA; p=0·04). In response to acid infusion, their pain threshold in the upper oesophagus fell further and for longer (mean fall in area under threshold/time curve 26·7 [11·0 to 42·3] vs 5·8 [2·8 to 8·8] units; p=0·04).

Interpretation

The finding of secondary viscerovisceral and viscerosomatic pain hypersensitivity suggests that central sensitisation may contribute to visceral pain disorders. The prolonged visceral pain hypersensitivity in patients with noncardiac chest pain suggests a central enhancement of sensory transfer. New therapeutic opportunities are therefore possible.

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.

Section snippets

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

References (24)

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