Patients with nonerosive gastroesophageal reflux disease often have relatively low esophageal acid exposure and respond suboptimally to gastric acid suppressi on. In these patients, other constituents of gastric contents may induce esophag eal symptoms.We have demonstrated that gastric contents can cause heartburn when the gastric pH > 4. (Aliment Pharm Ther 14:129-134, 2000). The aim of this stu dy was to determine relative sensitivities to chenodeoxycholic and ursodeoxychol ic acids, and 0.1 N HCl, administered as provocative perfusion tests. Patients w ith functional heartburn and healthy control subjects were evaluated. Patients u nderwent a modified Bernstein acid infusion test and esophageal Barostat balloon distention. Time and volume to pain were recorded. Barostat balloon distention was performed using our standard protocol.Step- wise distentions were performed and pain was recorded.Sensitivity to chenodeox ycholic acid (Cheno) and Ursodeoxycholic acid (Urso) were assessed similarly to the Bernstein test using 2 mM concentrations of each, followed immediately by 5 mM if no pain was reported with 2 mM. Volume of bile acid infusion and length of time until pain was induced were assessed and compared to the same endpoints fo r acid sensitivity. “Total“time and “total” volume to induce pain were calcula ted for Cheno and Urso. Least-squares means were generated and twotailed t-tes ts and regression analyses were performed (P< 0.05 l- evel of significance). Ten functional heartburn patients and six healthy contr ols were evaluated (3M, 13 F; age range, 19 to 56 years). Since five of six cont rols had pain with ac- id infusion(hypersensitive), all subjects were analyzed as one group. Only thr ee subjects (all controls) had no pain with infusion of 2 mM Cheno and received the follow-up infusion of 5 mM. These same three subjects tolerated the maximum infusion (150 ml and 15 min) of 5 mM Cheno. Nine subjects did not have pain wit h 2 mM Urso and received the follow-up infusion of 5 mM Urso(five functional he artburn, four controls). Significantly moresubjects tolerated the maximum bile a cid infusion of 2 mM Urso vs 2 mM Cheno (nine vs three; P< 0.05, Chi-square tes t).T- he pain threshold (volume and time) for Urso was significantly higher than tha t for Cheno and acid (P< 0.05), and the pain threshold for Cheno was significant ly higher than that for acid(P< 0.05). Conclusions are as follows: (1) Bile acids differ in their ability to induce pain. (2) Changing bile acid composition by treatment with Urso may change symptom presentation and symptom s everity in patients with bile acid-induced esophageal pain. Patients with nonerosive gastroesophageal reflux disease often have relatively low esophageal acid exposure and respond suboptimally to gastric acid suppressi on. In these patients, other constituents of gastric contents may induce esophag eal symptoms. > 4. (Aliment Pharm Ther 14: 129-134, 2000). The aim of this stu dy was to determine relative sensitivities to chenodeoxycholic and ursodeoxycholic acids, and 0.1 N HCl, administered as provocative perfusion tests. Patients w ith functional heartburn and healthy control subjects were were evaluated. Patients were normwent a modified Bernstein acid infusion test and esophageal Barostat balloon distention. Time and volume to pain were recorded. Barostat balloon distention was performed using our standard protocol. . Sensitivity to chenodeox ycholic acid (Cheno) and Ursodeoxycholic acid (Urso) were assessed sim ilarly to the Bernstein test using 2 mM concentrations of each, followed immediately by 5 mM if no pain was reported with 2 mM. Volume of bile acid infusion and length of time until pain was induced were assessed and compared to the same endpoints fo r acid “Total” time and “total” volume to induce pain were calcula ted for Cheno and Urso. Least-squares means were generated and twotailed t-tes ts and regression analyzes were performed (P <0.05 l-evel of significance Since five of six cont rols had pain with ac-id infusion (hypersensitive), all subjects were analyzed as Only thr ee subjects (all controls) had no pain with infusion of 2 mM Cheno and received the follow-up infusion of 5 mM. These same three subjects tolerated the maximum infusion (150 ml and 15 min) of 5 mM Cheno Nine subjects did not have pain wit h 2 mM Urso and received the follow-up infusion of 5 mM Urso (five functional he artburn, four controls). Significantly more objects tolerated the maximum bile a cid infusion of 2 mM Urso vs 2 mM Cheno (nine vs three; P <0.05, Chi-square tes t) (P <0.05), and the pain threshold for Cheno was significant ly higher than that for acid (P <0.05). Conclusions of T-he pain threshold (volume and time) for Urso was significantly higher than tha for Cheno and acid are as follows: (1) Bile acids differ in their ability to induce pain. (2) Changing bile acid composition by treatment with Urso may change symptom presentation and symptom s ever in in patients with bile acid-induced esophageal pain.