| Background Globus is a common functional esophageal disorder in clinics and ranked as A4 according to the Rome IV consensus criteria.With a high incidence of this disease,the etiology of globus is still unknown but appears to be multi-factorial,it has been attributed to the esophageal motility disorders,esophageal hypersensitivity,brain gut axis dysfunction and psychological factors.Furthermore,due to the uncertain etiology of globus,it remains difficult to establish standard investigation and treatment strategies for affected patients.What's worse,empirical antacid treatment as well as pharyngitis medicine remained to be the mainstay of treatment in many globus patients,but appear to produce no or only partial relief of symptoms.However,more and more studies confirmed that antidepressant agents are frequently used in patients with functional gastrointestinal disorders(FGIDs)as well as globus and showed a promising efficacy in alleviating globus symptoms,improving patients' psychological state and enhancing patients' quality of life.The antidepressant treatments for globus are becoming a hotspot in the current research,but the influence of these therapies on the esophageal motility as well as the brain gut axis of globus patients is still rarely reported.Objective To further explore the etiological relationship between globus and esophageal motility and brain gut peptide.And then evaluating the efficacy of antidepressant treatments for globus patients as well as the influence of these therapies on theesophageal motility as well as the brain gut axis of globus patients.Methods Globus patients were randomized into paroxetine group;amitriptyline group and lansoprazole group for 4-week treatment.All the subjects were asked to complete high resolution manometry and the following questionnaires pre-and post-therapy: Glasgow Edinburgh Throat Scale(GETS),Hamilton Rating Scale Anxiety/ Depression and Pittsburgh Sleep Quality Index.And the plasma levels of CGRP,NPY,SP were measured by the enzyme-linked immunosorbent assay before and after 4-week treatment.Treatment response was defined as a > 50% reduction in the GETS score.Results Part One: 1.One hundred and twenty patients completed high resolution manometry.24.2%(29/120)globus patients have high UES resting pressure,while 33.3%(40/120)globus patients have high UES residual pressure.Hypertensive UES patients have longer symptom duration(42.17±50.11 vs 20.67±17.07),more severe symptom(11.79±3.49 vs 7.81±2.12),higher UES resting pressure(131.38±22.38 vs 66.83±16.98),higher HAMA scores(13.59±2.84 vs 8.08±1.46),compared with non-hypertensive UES group(all P <0.05).2.The plasma levels of CGRP was higher in globus patients than that in health controls group(P<0.05),but there is no significant difference between hypertensive UES patients and non-hypertensive UES group(P>0.05).The plasma levels of NPY was significantly lower in hypertensive UES group than that in health controls group as well as non-hypertensive UES group(all P<0.05),furthermore,the plasma levels of NPY was also significantly lower in non-hypertensive UES group than that in health controls group(P<0.05).The plasma levels of SP was significantly higher in hypertensive UES group than that in health controls group as well as non-hypertensive UES group(all P<0.05),furthermore,the plasma levels of SP was also significantly higher in non-hypertensive UES group than that in health controls group(P<0.05).Part Two: 1.One hundred and fifteen patients completed the treatment study,of which 38 patients in RT group,40 patients in AMT group and 37 patients in PAR group.After 4-week treatment,86.5% of PAR group(32/37)were calculated as treatment response,significantly higher than that in AMT group(62.5%,25/40)and RT group(23.7%,9/38).2.After 4-week treatment,the scores of GETS,HAMA-14,HAMD-17 and PSQI in PAR group were significantly decreased when compared with the baseline(all P<0.05).The GETS score,HAMA-14 score as well as the PSQI score in AMT group were also decreased significantly(all P<0.05),while the HAMD score was no significant change(P>0.05).There was only the GETS score decreased significantly in RT group(all P<0.05).The scores of HAMA-14,HAMD-17 and PSQI in RT group were no significant difference between pretreatment and after 4-week therapy(all P>0.05).3.After 4-week treatmeat,the UES resting pressure was significantly decreased in PAR group and AMT group(all P<0.05),while there is no significant change in RT group(P>0.05).No significant changes of UES residual pressure were observed among these three groups after 4-week therapy(all P>0.05).4.After 4-week treatment,the plasma CGRP levels and the plasma SP levels were significantly decreased in PAR group(all P<0.05),while there was only the plasma SP levels decreased(P<0.05),and the plasma CGRP levels was no obvious change(P>0.05).The plasma NPY levels was significantly increased in PAR group and AMT group(all P<0.05),while the plasma NPY levels was higher in PAR group than that in AMT group after 4-week treatment(P<0.05).The plasma levels of CGRP,NPY,SP in RT group were no significant difference between pretreatment and after 4-week therapy(all P>0.05).Conclusion 1.Hypertensive UES was not rare among globus pharygeus patients.Compared with the non-hypertensive UES patients,Hypertensive UES globus patients have more severe symptom,obvious psychological and sleep disorders,and an evidentunbalanced brain-gut peptide levels.2.The antidepressant therapies could not only alleviate the globus symptom,improve patients' psychological state and sleep quality,but also improve patients' esophageal motility,decrease UES resting pressure,and rebalance the brain-gut interaction.However,the effectiveness of PAR therapy is obviously superior to the low-dose AMT therapy. |
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