Effect of hydrochloric acid and alcohol on duodenal chemosensitivity: Duodenal acid exposure paradoxically reduces chemosensitivity

Introduction: Chemosensitivity for capsaicin that is independent from mechanosensitivity has recently been demonstrated in the duodenum. Capsaicin stimulates the polymodal vanilloid receptor of type 1 (VR1) on nociceptive afferent neurons and induces pain and non-painful sensation. Other stimulators of VR1 include heat, acid, or alcohol.

Aims: The aims of the study were to evaluate the effects of duodenal acid and alcohol exposure on chemo- and mechanosensitivity. Methods: N=17 healthy subjects swallowed a tube assembly with an infusion site and a barostat in the mid-duodenum for pressure controlled random distension and capsaicin perfusion (40! g/ml, 2.5ml/min).

Studies were performed on two occasions, 1 week apart: in the HCl-group (N=8), studies were performed during infusion of either hydrochloric acid (HCl; 0,1mmol/l) or normal saline; the ETOH-group (N=9) received ethanol (5% vol/vol) and normal saline infusions, respectively. A graded questionnaire that evaluated quality and intensity of eight upper abdominal symptoms was filled out during distension and capsaicin infusion. Student's t'tests for paired observations were performed, p-values <0.05 were considered significant, data are given as mean±SEM; NS=not significant.

Results: The table shows latency to discomfort (in minutes) and perception scores reported 20 minutes after start of capsaicin infusion for both study groups. In the HCl-group, duodenal distension induced discomfort at intraballoon pressures of 37±11mmHg (HCl) and 35±7mmHg (NaCl) (NS) and volumes of 146±28ml and 149±20ml, respectively (NS). Similarly in the ETOH-group, balloon pressures (29±7 vs. 33±8mmHg) and volumes (141±32 vs. 143±39ml) to induce discomfort were not significantly different during ethanol and NaCl infusion, respectively.

Compliance was also not altered by the infusions.

Conclusion: Duodenal chemonociception is reduced during acid exposure, while ethanol has no effect on chemonociception. Mechanosensitivity remains unaltered by duodenal acid and ethanol exposure. Duodenal acid activates mechanisms that lead to a decreased sensitivity for intraluminal capsaicin, possibly by thickening the mucosal protective layer and impairing capsaicin permeation. This mechanism might protect duodenal chemonociceptors from being sensitised by acid. Whether this mechanism is impaired in patients with upper gastrointestinal functional disease remains to be determined.

	HCL-group		ETOH-group
	Discomfort (min)	Perception af ter 20min	Discomfort (min)	Perception after
Verum	44±16	9±9	30±22	13
Placebo	26±9	19±4	31±16	12
p-value	0.006	0.008	0.83	0.82