Introduction and rationale:
11-20% of patients undergoing abdominal surgery develop chronic abdominal pain. Adhesions
are the most common cause of chronic abdominal complaints after surgery. Chronic pain
from adhesions has devastating consequences for quality of life, and one in three
patients with pain from adhesions is opioid dependent.
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 a recent study we demonstrated that in selected patients adhesion-related pain can
effectively be treated by operation with adhesiolysis and application of an adhesion
barrier. However, almost 50% part of patients with adhesion-related pain are not
considered a candidate for surgical treatment, for various reasons.
Exploring the mechanisms that contribute to development of pain in patients with
adhesions could provide novel targets for medical therapies. These could greatly benefit
many patients suffering from adhesion- related pain. Two factors that might explain why
some patients with adhesions develop chronic pain are activation of molecular mechanisms
involved in chronic pain and stimulation of nerve fibers present in adhesions.
Specifically type C nerve fibres are associated with development of neuropathic pain.
Further we will also explore differences in microbioma, which has recently been
demonstrated to have an important role in a variety of abdominal conditions.
Adhesion formation at the molecular level involves a complex interaction of mediators.
One such mediator that might link adhesion formation to nociception is the
pro-inflammatory peptide substance P.(1) Substance P in turn is mediated by Transient
Receptor Potential Vanilloid (TRPV1), which is known to be upregulated in many conditions
associated with chronic pain. There is currently much research in developing new
analgesics targeting this receptor. Previous studies have shown that nerve fibres can be
present in adhesive tissue. Presence of such fibres, and especially type C fibres might
be responsible for a neuropathic type of pain. Stimulation of TRPV1 might also activate
type C nerve fibre endings.
Objective:
Quantify and compare expression of molecular mediators (such as TRPV-1, SP, and the
neurokinin receptor) and histological characteristics of adhesions from patients with
postoperative adhesions with and without chronic abdominal pain. Comparison of microbioma
in fecal samples between patients with adhesions with and without chronic abdominal pain
Study design:
This is a prospective observational cohort study.
Study population:
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. 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.
Study procedures:
Prior to surgery patients are requested to take a stool sample. During surgery
histological samples of adhesions will be taken during adhesiolysis in both groups. In
the control group histological samples of adhesions will only be taken if it does not
require extension of the incision and if it is not accompanied with additional risk of
intraoperative complications other than necessary for their planned surgery.
Main study parameters/endpoints:
Primary outcome mRNA expression levels of TRPV1 by quantitative polymerase chain reaction
(qPCR) compared between patients with and without chronic pain. Secondary outcomes are
TRPV1 protein levels (measured by Westernblot), SP, and neurokinin expression, and the
amount and types of nerve fibres found at histological assessment. Further we will
explore microbioma in feca samples.
Nature and extent of the burden and risks associated with participation, benefit and
group relatedness:
Taking fecal and histological samples for this study does not result in additional
operative risk. Adhesiolysis is often performed during any type of abdominal reoperation.
Histological samples in controls are only taken from adhesions that are easily accessible
and not from dense adhesions in close proximity to bowel or other vulnerable organs. No
additional adhesiolysis apart from biopsy will be performed.
