Review article: the clinical relevance of transient lower oesophageal sphincter relaxations in gastro-oesophageal reflux disease

The Participation of the Nitrergic Pathway in Increased Rate of Transitory Relaxation of Lower Esophageal Sphincter Induced by Rectal Distension in Dogs

“…Thus the objective criteria used to identify TLESR during our experiments were based on the manometric profile of the LES (8) . This technique enables continuous measurement of LES pressure and leading to a better comprehension of GERD, by identifying TLESR as the main permissive mechanism for GERD (18) .…”

Gastroesophageal Reflux Disease and Dental Erosions - A Mini Review

“…The most important mechanism is the failure of the anti-reflux barrier, known as lower esophageal sphincter (LES), which is composed by the own esophageal muscle and the diaphragmatic crus. The transient LES relaxation (TLESRs) triggered during post-prandial gastric distension is the main event during which the gastric content is propelled into the esophagus [8,9]. Furthermore, several risk factors have been associated with GERD, in particular obesity, dietary habits and emotional disturbances [10].…”

E3710, Long-Acting PPI as New Approach for the Treatment of Unmet Medical Needs for GERD

“…Many receptors in central nervous system is involved in TLESR, hence several approaches for TLESR inhibitors mediated through GABAB, metabolic glutamine (mGlu) and cannabinoid (CB) receptors have been developed to enhance the lower esophageal sphincter constriction for blocking the gastric acid and non-acid reflux. Although GABAB receptor agonist (baclofen, R-baclofen, AZD9343, lesogaberan: AZD3355), mGlu receptor 5 antagonist (ADX10059, AZD2066, AZD2516) and CB1 agonist (D9-THC) reduced the TLESR, central nerve side effects such as headache and drowsiness, and low compliance (need to be taken twice or three times a day) were observed in clinical studies [Blondeau, 2010;Kessing et al, 2011]. Lesogaberan which was administered twice daily as add-on treatment to PPI ameliorated heartburn and regurgitation symptoms in persistent GERD symptoms even daily PPI therapy [Boeckxstaens et al, 2011]; however these effects were not adequate.…”

“…TLESR is an episode of lower esophageal relaxation that occurs unrelated to swallowing [Kessing et al, 2011], and it is considered to be the underlying refractory factors for GERD treatment with PPIs. Many receptors in central nervous system is involved in TLESR, hence several approaches for TLESR inhibitors mediated through GABAB, metabolic glutamine (mGlu) and cannabinoid (CB) receptors have been developed to enhance the lower esophageal sphincter constriction for blocking the gastric acid and non-acid reflux.…”