Characterization of Rebound Pain Following Peripheral Nerve Block and Its Association With Gut Microbiome Diversity

August 19, 2017 updated by: Dr. David Brenner, Cork University Hospital

The objective of this study is to determine the association between gut microbiome diversity and the characteristics of rebound pain at offset of peripheral nerve block in patients who have undergone upper limb surgery. Other purposes of this study are to determine associations between gut microbiome constitution and persistent post-surgical pain; and describing rebound pain by quantifying its clinical, psychological and neurophysiological characteristics in this patient cohort.

Study Overview

Status

Completed

Conditions

Detailed Description

Based on an emerging understanding of the importance of the gut microbiome in the human and animal responses to stress, it is clear that gut microbiota influence bidirectional signaling between the central nervous system (CNS) and gut (microbiota-gut-brain axis). One element of this influence is the role of gut microbiota in visceral hypersensitivity and pain. Important clinical implications of this understanding have begun to emerge: for instance irritable bowel syndrome (IBS) patient cohorts demonstrate distinct gut microbiome characteristics and, in pre-clinical models, manipulation of the gut microbiome lessens visceral hypersensitivity. To date, attempts to improve pain symptoms in IBS using probiotics have been modestly and variably successful.

One research area which offers potential to the discovery of novel analgesic therapies is the activation of endogenous opiate pain processing including augmentation of descending inhibition. (Broadly, identification of new targets/alkaloid modification/ proteomics efforts have been unsuccessful). Manipulation of microbiota-gut-brain axis by administering probiotics offers one potential route for such activation. There are many of examples of such manipulation altering animal behavior and physiology. In theory, opportunities for such manipulation might exist during or close to early life stress or before noxious stimuli such as elective surgery.

The relationship between the gut microbiome and somatic or neuropathic pain has not been studied. Certain of the pathways and regulators of visceral pain and hypersensitivity are also critical in somatic pain handling. These include peripheral sensitization of primary sensory afferents, central sensitization in particular of spinal ascending neurons and alteration of descending inhibitory pathways. These neuroplastic changes have been well documented in the surgical setting in the examination of persistent post-surgical pain.

"Rebound pain" is a quantifiable difference in pain scores when the block is working, versus the increase in acute pain that is encountered during the first few hours after the effects of perineural single-injection or continuous infusion local anesthetics resolve. Rebound pain may represent a manifestation of hypersensitivity and offer an accessible clinical model suitable for examining the association between gut microbiome diversity and perioperative neuroplastic changes.

Study Type

Observational

Enrollment (Actual)

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Ireland
- Co. Cork
  - Cork, Co. Cork, Ireland
    - Division of Anaesthesia and Intensive Care, Cork University Hospital
  - Cork, Co. Cork, Ireland
    - Department of Anaesthesiology, South Infirmary-Victoria University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

ASA I-II patients scheduled to undergo upper limb surgery under brachial plexus block will be recruited.

Description

Inclusion Criteria:

Age 18-80 years
Patients undergoing hand surgery for Dupuytren's contracture correction or open reduction and internal fixation of distal radius fracture under axillary brachial plexus block

Exclusion Criteria:

Contraindication of regional anaesthesia, patient is allergic to local anesthetics
Chronic pain syndrome
History of peripheral neuropathy
Preexisting nerve damage in the operated arm (sensory or motor deficit)
Axillary surgery in the past
Uncontrolled pain (Verbal Rating Score ≥5 out of 10 at rest despite adequate analgesic measures)
Clinically significant cognitive impairment (Minimental state score < 24)
Language barrier
Depression
Diabetes
Obesity (BMI>35)
Antibiotic therapy in the preceding 30 days
Probiotics

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Association between gut microbiome α diversity and the magnitude of rebound pain (Numerical Rating Scale) Time Frame: Perioperative period	Perioperative period

Secondary Outcome Measures

Outcome Measure	Time Frame
Association between gut microbiome α diversity and magnitude of postoperative pain (Numerical Rating Scale). Time Frame: Perioperative period	Perioperative period
Association between gut microbiome α diversity and analgesic consumption (mg/24 hours). Time Frame: Perioperative period	Perioperative period
Association between gut microbiome α diversity and salivary cortisol concentration (ng/ml). Time Frame: Perioperative period	Perioperative period
Association between gut microbiome α diversity and Pain Perception Threshold (PPT, mAmp). Time Frame: Perioperative period	Perioperative period
Association between gut microbiome constitution (α diversity) and incidence of persistent post-surgical pain. Time Frame: Up to 4 weeks postoperatively	Up to 4 weeks postoperatively
Pearson's correlation coefficient for i. Maximum Numerical Rating Scale (NRS) score for rebound pain vs. ii. Pain Perception Threshold (PPT, mAmp) and Pain Tolerance Threshold (PTT, mAmp) based on Quantitative Sensory Testing. Time Frame: Up to 48 hours postoperatively	Up to 48 hours postoperatively

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Cork University Hospital

Investigators

Study Chair: George Shorten, Professor, Professor of Anaesthesia and Intensive Care Medicine, Consultant Anaesthetist, University College Cork / Cork University Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2016

Primary Completion (Actual)

June 16, 2017

Study Completion (Actual)

June 16, 2017

Study Registration Dates

First Submitted

November 28, 2016

First Submitted That Met QC Criteria

December 15, 2016

First Posted (Estimate)

December 20, 2016

Study Record Updates

Last Update Posted (Actual)

August 22, 2017

Last Update Submitted That Met QC Criteria

August 19, 2017

Last Verified

August 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

GMB-RP

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

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