Nociceptors, Neurotrophic Factors and Cytokine Expression in Gastroesophageal Reflux Disease

Study Overview
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Brief Summary
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Transient receptor potential vanilloid-1 (TRPV1) receptor and proteinase-activated receptor 2 (PAR2) have been implicated in the mechanism of acid induced inflammation in gastroesophageal reflux disease (GERD). We aimed to evaluate TRPV1 and PAR2 mRNA expression levels in the GERD patients and their relationship with endoscopic findings and reflux symptoms.

Detailed Description
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All the subjects receive upper GI endoscopy and completed questionnaires about GERD symptoms under the supervision of a well-trained interviewer. Subjects are excluded if there was a history of gastrointestinal surgery, Barrett's esophagus, esophageal motility disorder, duodenal ulcer, benign gastric ulcer or gastroduodenal cancer and if he or she had any history of systemic disease requiring chronic medication (except for hypertension and diabetes mellitus). The subjects are classified into 3 groups after upper GI endoscopy and completing questionnaires about GERDsymptoms ; ERD(erosive reflux disease), NERD(nonerosive reflux disease) and control group.

Official Title
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Symptomatic Gastroesophageal Reflux Disease is Associated With Increased TRPV1 and PAR2 mRNA Expression Levels in the Esophageal Mucosa

Conditions
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Gastro-esophageal Reflux Disease

Intervention / Treatment
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* Procedure: endoscopic mucosal biopsy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: subjects who completed upper GI endoscopy and questionnaires about GERD symptoms Exclusion Criteria: a history of gastrointestinal surgery Barrett's esophagus esophageal motility disorder duodenal ulcer benign gastric ulcer gastroduodenal cancer if he or she had any history of systemic disease requiring chronic medication (except for hypertension and diabetes mellitus).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: control group<br>Subjects who do not show mucosal breaks in the upper GI endoscopy consistent with reflux esophagitis and do not complain of GERD symptoms. Endoscopic mucosal biopsy was done for every subject. | Procedure: endoscopic mucosal biopsy<br>* endoscopic mucosal biopsy was undertaken for every participant.<br>|
| Active Comparator: ERD group<br>Subjects who have mucosal breaks in the upper GI endoscopy consistent with reflux esophagitis and/or complain of GERD symptoms. Endoscopic mucosal biopsy was done for every subject. | Procedure: endoscopic mucosal biopsy<br>* endoscopic mucosal biopsy was undertaken for every participant.<br>|
| Active Comparator: NERD group<br>Subjects who do not have mucosal breaks in the upper GI endoscopy consistent with reflux esophagitis and complain of GERD symptoms. Endoscopic mucosal biopsy was done for every subject. | Procedure: endoscopic mucosal biopsy<br>* endoscopic mucosal biopsy was undertaken for every participant.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TRPV1, GDNF, and NGF mRNA Expression of Esophageal Mucosa | The primers used in real-time qPCR were designed using PrimerExpress Software V2.0 (Applied Biosystems, Foster City, CA, USA) based on sequence information from the National Center for Biotechnology Information database. Real-time qPCR was performed in triplicate by using a StepOnePlus Real-time PCR (Applied Biosystems) with SYBR Premix Ex TaqTM (Takara Bio, Shiga, Japan) according to manufacturers' instructions and protocols. Thermal cycling was performed as follows: initial denaturation at 95 °C for 10s followed by 40 cycles of 95 °C for 5 s and 60 °C for 33s. Homo b-actin was used as a reference; i.e. each sample was normalized on the basis of its b-actin content. The relative change in all target genes expression was determined by the fold-change analysis. | up to 24weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PAR2 and IL-8 Expression of Esophageal Mucosa | The primers used in real-time qPCR were designed using PrimerExpress Software V2.0 (Applied Biosystems, Foster City, CA, USA) based on sequence information from the National Center for Biotechnology Information database. Real-time qPCR was performed in triplicate by using a StepOnePlus Real-time PCR (Applied Biosystems) with SYBR Premix Ex TaqTM (Takara Bio, Shiga, Japan) according to manufacturers' instructions and protocols. Thermal cycling was performed as follows: initial denaturation at 95 °C for 10s followed by 40 cycles of 95 °C for 5 s and 60 °C for 33s. Homo b-actin was used as a reference; i.e. each sample was normalized on the basis of its b-actin content. The relative change in all target genes expression was determined by the fold-change analysis. | up to 24weeks |