Histological and Molecular Mechanisms of Pain in Patient With Chronic Pain From Adhesions

NCT03938168 | Completed

• 1 other identifier: 2018-4801
• Study Type: observational
• Target: 61
• Locations: 1 country
• Sites: 3

Brief Summary

11-20% of patients undergoing abdominal surgery develop chronic abdominal pain. Adhesions are a common cause of chronic pain following surgery. Adhesions develop after up to 90% of laparotomies and 70% of laparoscopic surgeries. Obviously, not all adhesions cause pain. It is still poorly understood why adhesions cause pain in some patients, while other patients with adhesions experience no pain. In this study we explore possible mechanism through which adhesions might cause pain. For this purpose we will assess expression of molecular mediators (such as TRPV-1, SP, and the neurokinin receptor), histological characteristics, and fecal microbioma that might be associated with pain.Expression of these factor will be compared to sample from 30 patients with chronic pain attributed to adhesions, and 30 patients undergoing a reoperation with adhsiolysis for reasons unrelated to pain.

Conditions

Tissue Adhesion; Chronic Pain; Surgery

Outcome Measures

Primary Outcomes (1)

• TRPV-1

  mRNA expression levels of TRPV1 by quantitative polymerase chain reaction (qPCR)

  during surgery

Secondary Outcomes (5)

• TRPV-1 protein

  during surgery

• SP

  during surgery

• NK-1

  during surgery

• Nerve fibers

  during surgery

• Microbioma

  12 months

Study Arms (2)

Pain patients

30 patients eligible for adhesiolysis because of chronic adhesion-related pain. Patients are recruited at the RadboudUMC, MUMC+ and Pantein hospital departments of surgery. These are patients with chronic pain after previous abdominal surgery who have been selected for operative treatment after evaluated with CineMRI. CineMRI is used to map adhesions. This technique has been established to provide insight in localization of adhesions in relation to the pain, and risk of bowel injury based on extensiveness of adhesions.

Diagnostic Test: Biopsy, fecal sample

Control group

The control group will comprise of 30 patients undergoing an abdominal reoperation during which adhesiolysis has to be performed for reasons other than chronic adhesion-related pain.

Diagnostic Test: Biopsy, fecal sample

Interventions

Biopsy, fecal sample DIAGNOSTIC_TEST

Preoperatively and at 12 months after surgery, patients will obtain a fecal stool sample for microbioma analysis. Adhesions that are cut and released to acquire access to the operative field are stored for molecular and histological analyses.

Control group; Pain patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Chronic abdominal pain after surgery is a frequent condition.(13) At present the RadboudUMC, MUMC+, and Pantein hospital departments of surgery annually evaluate 60-80 patients each for chronic pain by cineMRI. Between 30-40 of these patients are expected to undergo surgical treatment. Yearly between 600-700 patients will undergo an elective abdominal reoperation at the participating departments of surgery. Thus there is ample surgical volume for this study.

You may qualify if:

• Patients between 18 and 75 years old scheduled for elective abdominal reoperation
• No present chronic abdominal pain
• No other diseases or syndromes that cause chronic pain (e.g. rheumatic arthritis)

You may not qualify if:

• A potential subject with chronic pain will be excluded from participation in this study in the following cases:
• Contra-indications for general anaesthesia and re-operation
• Inability to acquire informed consent

Sponsors & Collaborators

• Radboud University Medical Center: lead
• Maastricht University Medical Center: collaborator
• Maas Hospital Pantein: collaborator

Study Sites (3)

Maasziekenhuis Pantein

Boxmeer, Gelderland, 5830 AB, Netherlands

Location

Radboud University Medical Center

Nijmegen, Gelderland, 6500HB, Netherlands

Location

Maastricht Universitair Medisch Centrum+

Maastricht, Limburg, 6202 AZ, Netherlands

Location

Related Publications (5)

• van den Beukel BAW, Stommel MWJ, van Leuven S, Strik C, IJsseldijk MA, Joosten F, van Goor H, Ten Broek RPG. A Shared Decision Approach to Chronic Abdominal Pain Based on Cine-MRI: A Prospective Cohort Study. Am J Gastroenterol. 2018 Aug;113(8):1229-1237. doi: 10.1038/s41395-018-0158-9. Epub 2018 Jun 27.

  PMID: 29946174 BACKGROUND

• Reed KL, Fruin AB, Bishop-Bartolomei KK, Gower AC, Nicolaou M, Stucchi AF, Leeman SE, Becker JM. Neurokinin-1 receptor and substance P messenger RNA levels increase during intraabdominal adhesion formation. J Surg Res. 2002 Nov;108(1):165-72. doi: 10.1006/jsre.2002.6533.

  PMID: 12443729 BACKGROUND

• ten Broek RP, Issa Y, van Santbrink EJ, Bouvy ND, Kruitwagen RF, Jeekel J, Bakkum EA, Rovers MM, van Goor H. Burden of adhesions in abdominal and pelvic surgery: systematic review and met-analysis. BMJ. 2013 Oct 3;347:f5588. doi: 10.1136/bmj.f5588.

  PMID: 24092941 BACKGROUND

• Keszthelyi D, Troost FJ, Jonkers DM, Helyes Z, Hamer HM, Ludidi S, Vanhoutvin S, Venema K, Dekker J, Szolcsanyi J, Masclee AA. Alterations in mucosal neuropeptides in patients with irritable bowel syndrome and ulcerative colitis in remission: a role in pain symptom generation? Eur J Pain. 2013 Oct;17(9):1299-306. doi: 10.1002/j.1532-2149.2013.00309.x. Epub 2013 Mar 25.

  PMID: 23529955 BACKGROUND

• Scotland RS, Chauhan S, Davis C, De Felipe C, Hunt S, Kabir J, Kotsonis P, Oh U, Ahluwalia A. Vanilloid receptor TRPV1, sensory C-fibers, and vascular autoregulation: a novel mechanism involved in myogenic constriction. Circ Res. 2004 Nov 12;95(10):1027-34. doi: 10.1161/01.RES.0000148633.93110.24. Epub 2004 Oct 21.

  PMID: 15499026 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Samples from adhesions are taken. Fecal samples are taken for microbioma analysis.

MeSH Terms

Conditions

Tissue Adhesions; Chronic Pain

Interventions

Biopsy

Condition Hierarchy (Ancestors)

Cicatrix; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Richard P ten Broek, MD, PhD

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

• Harry van Goor, MD, PhD

  Radboud University Medical Center

  STUDY DIRECTOR

• Richard P ten Broek, MD, PhD

  Radboud University Medical Center

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 1, 2019
• First Posted: May 6, 2019
• Study Start: April 9, 2019
• Primary Completion: December 31, 2023
• Study Completion: December 20, 2024
• Last Updated: December 31, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE
• Time Frame: 12 months after publication of primary results

Locations

NL (3)