The work presented in this thesis concerns neurophysiology and pharmacology of the oesophageal afferent pathways involved in oesophago-pharyngeal reflexes and oesophageal nociception. Disturbances of reflexes governing contractile and relaxation responses of the upper oesophageal sphincter (DOS) are likely to be implicated in the pathophysiology of conditions involving excessive oesophago-pharyngeal regurgitation, impaired oesophageal clearance, and an abnormal belch reflex. Visceral hypersensitivity, a heightened perception of gastrointestinal sensation is frequently observed in functional gastrointestinal disorders and provides compelling evidence that it plays an important role in the pathogenesis of functional heartburn and non-erosive reflux disease. The work in this thesis explores the neurophysiology, pharmacology and pathophysiology of oesophago-DOS reflexes in humans by experimentally inducing DOS relaxations in healthy controls and patients with reflux laryngitis, and by recording DOS motor responses during spontaneous oesophago-pharyngeal regurgitation. Nociception was assessed by measuring oesophageal sensitivity to electrical stimulation and oesophageal acid perfusion in healthy controls, which was then compared with several heartburn populations (functional heartburn, erosive and non-erosive reflux disease). Additional studies were performed to evaluate the potential role of intraluminal impedance in defining antegrade bolus flow through the pharyngo-oesophageal segment during swallowing as a prelude to the adaptation of the technique to find a more accurate method for the detection of oesophago-pharyngeal regurgitation. The main findings from this work are as follows. 1) Mucosal lignocaine-sensitive afferents mediate the distension-induced oesophago-DOS relaxation reflex and lignocaine insensitive, presumably muscular mechanoceptors, mediate the distension-induced oesophago-DOS contractile reflex. The latter reflex is also upregulated by oesophageal acidification indicative of a possible protective mechanism. 2) Prolonged studies in patients with proven oesophago-pharyngeal regurgitation demonstrated that the most common mechanism of oesophago-pharyngeal regurgitation is a transient, non-swallow related, relaxation of the DOS. 3) Experimental evaluation of the oesophago-DOS relaxation reflex revealed that it is upregulated in patients with reflux laryngitis, suggesting that the aberrant afferent signalling in the oesophagus may be a contributory factor mediating oesophago-pharyngeal regurgitation. 4) Measurement of oesophageal sensory thresholds in response to electrical stimulation and acid perfusion revealed that all patients, irrespective of the presence or absence of mucosal injury, exhibit acid-induced hypersensitisation. 5) The viscro-somatic referral pattern of acid- and electrically-induced chest pain is increased in patients with functional heartburn and non-erosive reflux disease. These findings support the hypothesis that central sensitisation of nociceptive pathways may contribute to symptom reporting in these heartburn populations.
| Identifer | oai:union.ndltd.org:ADTP/258419 |
| Date | January 2008 |
| Creators | Szcz??sniak, Michal Marcin, Clinical School - St George Hospital, Faculty of Medicine, UNSW |
| Publisher | Awarded by:University of New South Wales. Clinical School - St George Hospital |
| Source Sets | Australiasian Digital Theses Program |
| Language | English |
| Detected Language | English |
| Rights | Copyright Szcz??sniak Michal Marcin., http://unsworks.unsw.edu.au/copyright |
Page generated in 0.002 seconds