Exploring the neurophysiological basis of chest wall allodynia induced by experimental oesophageal acidification – evidence of central sensitization¹

Abstract

In somatic models of central sensitisation (CS) allodynia develops following changes to somatic A-beta fibres, allowing these afferents which normally only process innocuous sensations to encode pain. The aim of this study was to determine whether somatic allodynia induced by visceral sensitisation occurs via N-Methyl-D-Aspartate (NMDA) receptor mediated changes to the neurophysiological characteristics of somatic A-beta fibres. Twelve healthy subjects had oesophageal, chest wall and foot pain thresholds (PT) to electrical stimulation measured, and chest wall evoked potentials (CEP) recorded before and 30 minutes after distal oesophageal acidification on 2 separate visits. Intravenous ketamine (an NMDA receptor antagonist) or saline was given 30 minutes post acid with repeated oesophageal and chest wall PT measurements and CEP recordings. Distal oesophageal acidification reduced PT to electrical stimulation on the anterior chest wall (37 +/- 10 mA v 29 +/- 7 mA p = 0.01) and proximal oesophagus (46 +/- 10 mA v 33 +/- 11 mA p = 0.001) but not the foot (37 +/- 25 mA v 39 +/- 23 mA p = 0.12). The induction of chest wall somatic allodynia was accompanied by a reduction in the latency of the P1 (36 +/- 3 ms to 30 +/- 4 ms p = 0.016) and P2 (87 +/- 7 ms to v 76 +/- 7 ms p = 0.049) components of the CEP. NMDA receptor antagonism reversed both visceral and somatic pain hypersensitivity but did not affect CEP latencies. These data provide objective neurophysiological evidence that CS contributes to the development of somatic allodynia following visceral sensitisation.

The Esophageal Multimodal Pain Model: Normal Values and Degree of Sensitization in Healthy Young Male Volunteers

“…Acid stimulation has been used in several studies measuring electrical thresholds and 12-23% sensitization on group means has been measured using different methods and stimulation areas [28,42]. These results from previous studies stimulating high in the esophagus correspond well with those in the present study.…”

Neurophysiological evaluation of convergent afferents innervating the human esophagus and area of referred pain on the anterior chest wall

“…This results in A␤ fibers signaling to the sensitized region of the dorsal horn and innocuous stimuli being perceived as pain (37). We provided objective neurophysiological evidence to support this by recording somatosensory evoked potentials from the area of referred esophageal pain pre and postacid and showed that the amplitude of the somatosensory evoked potential increased and the latency decreased, demonstrating amplification of the large-diameter myelinated (A␤) fiber signaling pathway that is selectively activated at very low levels of electrical stimulation (34).…”

“…We have previously shown that esophageal acidification can induce somatic hypersensitivity and allodynia to electrical stimulation of the area or referred esophageal pain on the anterior chest wall (30,34). This somatic allodynia is thought to develop following esophageal tissue injury-induced central sensitization of spinal cord neurons.…”

“…We have previously shown that after sensitization of the esophagus with experimental acidification, central sensitization of spinal dorsal horn neurons occurs and large myelinated A␤ fibers that innervate the area of referred pain on the anterior chest wall become hypersensitive. These fibers normally only process innocuous tactile stimuli but once sensitized become capable of signaling pain, resulting in allodynia (34).…”

Human Experimental Pain Models for Assessing the Therapeutic Efficacy of Analgesic Drugs

“…Most of the studies on visceral hyperalgesia have demonstrated increased pain in response to one or more modalities after experimentally induced sensitization by chemicals (Sarkar et al, 2001(Sarkar et al, , 2003Drewes et al, 2003a;Hobson et al, 2004;Pedersen et al, 2004;Frøkjaer et al, 2005;Sami et al, 2006;Willert et al, 2007;Brock et al, 2009a).…”