Authors: willert, r. p.¹; delaney, c.¹; kelly, k.¹; sharma, a.¹; aziz, q.¹; hobson, a. r.²

Source: Neurogastroenterology and Motility, Volume 19, Number 4, April 2007 , pp. 270-278(9)

Publisher: Wiley-Blackwell

Abstract:

 

In somatic models of central sensitisation (CS) allodynia develops following changes to somatic A-β 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-β 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 ± 10mA v 29 ± 7mA p = 0.01) and proximal oesophagus (46 ± 10mA v 33 ± 11mA p = 0.001) but not the foot (37 ± 25mA v 39 ± 23mA p = 0.12). The induction of chest wall somatic allodynia was accompanied by a reduction in the latency of the P1 (36 ± 3ms to 30 ± 4ms p = 0.016) and P2 (87 ± 7 ms to v 76 ± 7ms 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.

Keywords: central sensitization:  chest wall-evoked potentials; N-methyl-d-aspartate receptor; visceral hypersensitivity

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1365-2982.2006.00890.x

Affiliations: 1: GI Sciences Department, University of Manchester, Hope Hospital, Salford, Lancs, UK 2: Neurology & GI CEDD, Clinical Pharmacology and Discovery Medicine, GSK R&D Ltd, Harlow, Essex, UK

Publication date: 2007-04-01

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