Pain, PostoperativeNCT02998177
Characterization of Rebound Pain Following Peripheral Nerve Block and Its Association With Gut Microbiome Diversity
An observational study of Pain, Postoperative and Gastrointestinal Microbiome, run by Cork University Hospital at 2 sites in Ireland.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Pain, Postoperative, Gastrointestinal Microbiome
- How many people
- 20 participants
- Where
- 2 sitesIreland
- Study dates
- Nov 2016to 16 Jun 2017
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: ASA I-II patients scheduled to undergo upper limb surgery under brachial plexus block will be recruited.
Who may be able to join
- 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
Who cannot join
- 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)
Show all 13Show fewer
- Clinically significant cognitive impairment (Minimental state score < 24)
- Language barrier
- Depression
- Diabetes
- Obesity (BMI>35)
- Antibiotic therapy in the preceding 30 days
- Probiotics
Trial locations and contacts
2 sites in 1 country.
Ireland2 sites
Department of Anaesthesiology, South Infirmary-Victoria University Hospital
Cork, Co. Cork
Division of Anaesthesia and Intensive Care, Cork University Hospital
Cork, Co. Cork
About this study
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.
Read the 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.
- Conditions
- Pain, Postoperative, Gastrointestinal Microbiome
- Keywords
- Postoperative pain, Rebound pain, Gut microbiome, Gut microbiota, Peripheral nerve block, Axillary brachial plexus block
- Medical subject headings
- Pain, Postoperative
What is being measured
The primary outcome is the main question the study is designed to answer.
Association between gut microbiome α diversity and the magnitude of rebound pain (Numerical Rating Scale)
Measured: Perioperative period
Secondary outcomes (6)
Association between gut microbiome α diversity and magnitude of postoperative pain (Numerical Rating Scale).
Measured: Perioperative period
Association between gut microbiome α diversity and analgesic consumption (mg/24 hours).
Measured: Perioperative period
Association between gut microbiome α diversity and salivary cortisol concentration (ng/ml).
Measured: Perioperative period
Association between gut microbiome α diversity and Pain Perception Threshold (PPT, mAmp).
Measured: Perioperative period
Association between gut microbiome constitution (α diversity) and incidence of persistent post-surgical pain.
Measured: 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.
Measured: Up to 48 hours postoperatively
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2016 (estimated)
- Study startNov 2016
- Primary completion16 Jun 2017
- Study completion16 Jun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Pain, PostoperativeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cork University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. David Brenner, Cork University Hospital
- Investigators
- George Shorten, Professor, Study chair, Professor of Anaesthesia and Intensive Care Medicine, Consultant Anaesthetist, University College Cork / Cork University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02998177
- Sponsor's protocol ID
- GMB-RP
- Status last verified
- Aug 2017
- First submitted
- 28 Nov 2016
- Last updated
- 22 Aug 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Enck P, Zimmermann K, Menke G, Klosterhalfen S. Randomized controlled treatment trial of irritable bowel syndrome with a probiotic E.-coli preparation (DSM17252) compared to placebo. Z Gastroenterol. 2009 Feb;47(2):209-14. doi: 10.1055/s-2008-1027702. Epub 2009 Feb 5.
PubMed 19197823Hsiao EY, McBride SW, Hsien S, Sharon G, Hyde ER, McCue T, Codelli JA, Chow J, Reisman SE, Petrosino JF, Patterson PH, Mazmanian SK. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell. 2013 Dec 19;155(7):1451-63. doi: 10.1016/j.cell.2013.11.024. Epub 2013 Dec 5.
PubMed 24315484Williams BA, Bottegal MT, Kentor ML, Irrgang JJ, Williams JP. Rebound pain scores as a function of femoral nerve block duration after anterior cruciate ligament reconstruction: retrospective analysis of a prospective, randomized clinical trial. Reg Anesth Pain Med. 2007 May-Jun;32(3):186-92. doi: 10.1016/j.rapm.2006.10.011.
PubMed 17543812Williams BA. Forecast for perineural analgesia procedures for ambulatory surgery of the knee, foot, and ankle: applying patient-centered paradigm shifts. Int Anesthesiol Clin. 2012 Winter;50(1):126-42. doi: 10.1097/AIA.0b013e31821a00d0.
PubMed 22227428Clarke SF, Murphy EF, O'Sullivan O, Lucey AJ, Humphreys M, Hogan A, Hayes P, O'Reilly M, Jeffery IB, Wood-Martin R, Kerins DM, Quigley E, Ross RP, O'Toole PW, Molloy MG, Falvey E, Shanahan F, Cotter PD. Exercise and associated dietary extremes impact on gut microbial diversity. Gut. 2014 Dec;63(12):1913-20. doi: 10.1136/gutjnl-2013-306541. Epub 2014 Jun 9.
PubMed 25021423Lapthorne S, Pereira-Fantini PM, Fouhy F, Wilson G, Thomas SL, Dellios NL, Scurr M, O'Sullivan O, Ross RP, Stanton C, Fitzgerald GF, Cotter PD, Bines JE. Gut microbial diversity is reduced and is associated with colonic inflammation in a piglet model of short bowel syndrome. Gut Microbes. 2013 May-Jun;4(3):212-21. doi: 10.4161/gmic.24372. Epub 2013 Apr 2.
PubMed 23549027O'Mahony SM, Marchesi JR, Scully P, Codling C, Ceolho AM, Quigley EM, Cryan JF, Dinan TG. Early life stress alters behavior, immunity, and microbiota in rats: implications for irritable bowel syndrome and psychiatric illnesses. Biol Psychiatry. 2009 Feb 1;65(3):263-7. doi: 10.1016/j.biopsych.2008.06.026. Epub 2008 Aug 23.
PubMed 18723164DuPont AW, DuPont HL. The intestinal microbiota and chronic disorders of the gut. Nat Rev Gastroenterol Hepatol. 2011 Aug 16;8(9):523-31. doi: 10.1038/nrgastro.2011.133.
PubMed 21844910Melzack R. The McGill Pain Questionnaire: major properties and scoring methods. Pain. 1975 Sep;1(3):277-299. doi: 10.1016/0304-3959(75)90044-5.
PubMed 1235985Melzack R. The McGill pain questionnaire: from description to measurement. Anesthesiology. 2005 Jul;103(1):199-202. doi: 10.1097/00000542-200507000-00028.
PubMed 15983473Stalder T, Kirschbaum C, Kudielka BM, Adam EK, Pruessner JC, Wust S, Dockray S, Smyth N, Evans P, Hellhammer DH, Miller R, Wetherell MA, Lupien SJ, Clow A. Assessment of the cortisol awakening response: Expert consensus guidelines. Psychoneuroendocrinology. 2016 Jan;63:414-32. doi: 10.1016/j.psyneuen.2015.10.010. Epub 2015 Oct 20.
PubMed 26563991
Study at a glance
From the registry record, last updated by the sponsor on 22 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Characterization of Rebound Pain Following Peripheral Nerve Block and Its Association With Gut Microbiome Diversity
- ClinicalTrials.gov ID
- NCT02998177
- Acronym / sponsor ID
- GMB-RP
- Conditions
- Pain, Postoperative, Gastrointestinal Microbiome
- Keywords
- Postoperative pain, Rebound pain, Gut microbiome, Gut microbiota, Peripheral nerve block, Axillary brachial plexus block
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Cork University HospitalUniversity, hospital or other
- Study start
- Nov 2016
- Primary completion
- 16 Jun 2017 (actual)
- Study completion
- 16 Jun 2017 (actual)
- First posted
- 20 Dec 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Observational model
- Case only
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- ASA I-II patients scheduled to undergo upper limb surgery under brachial plexus block will be recruited.
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Association between gut microbiome α diversity and the magnitude of rebound pain (Numerical Rating Scale)
Time frame: Perioperative period
6 secondary outcomes
Association between gut microbiome α diversity and magnitude of postoperative pain (Numerical Rating Scale).
Time frame: Perioperative period
Association between gut microbiome α diversity and analgesic consumption (mg/24 hours).
Time frame: Perioperative period
Association between gut microbiome α diversity and salivary cortisol concentration (ng/ml).
Time frame: Perioperative period
Association between gut microbiome α diversity and Pain Perception Threshold (PPT, mAmp).
Time frame: Perioperative period
Association between gut microbiome constitution (α diversity) and incidence of persistent post-surgical pain.
Time frame: 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2017.
- Background: PubMed 19197823Enck P, Zimmermann K, Menke G, Klosterhalfen S. Randomized controlled treatment trial of irritable bowel syndrome with a probiotic E.-coli preparation (DSM17252) compared to placebo. Z Gastroenterol. 2009 Feb;47(2):209-14. doi: 10.1055/s-2008-1027702. Epub 2009 Feb 5.
- Background: PubMed 24315484Hsiao EY, McBride SW, Hsien S, Sharon G, Hyde ER, McCue T, Codelli JA, Chow J, Reisman SE, Petrosino JF, Patterson PH, Mazmanian SK. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell. 2013 Dec 19;155(7):1451-63. doi: 10.1016/j.cell.2013.11.024. Epub 2013 Dec 5.
- Background: PubMed 17543812Williams BA, Bottegal MT, Kentor ML, Irrgang JJ, Williams JP. Rebound pain scores as a function of femoral nerve block duration after anterior cruciate ligament reconstruction: retrospective analysis of a prospective, randomized clinical trial. Reg Anesth Pain Med. 2007 May-Jun;32(3):186-92. doi: 10.1016/j.rapm.2006.10.011.
- Background: PubMed 22227428Williams BA. Forecast for perineural analgesia procedures for ambulatory surgery of the knee, foot, and ankle: applying patient-centered paradigm shifts. Int Anesthesiol Clin. 2012 Winter;50(1):126-42. doi: 10.1097/AIA.0b013e31821a00d0.
- Background: PubMed 25021423Clarke SF, Murphy EF, O'Sullivan O, Lucey AJ, Humphreys M, Hogan A, Hayes P, O'Reilly M, Jeffery IB, Wood-Martin R, Kerins DM, Quigley E, Ross RP, O'Toole PW, Molloy MG, Falvey E, Shanahan F, Cotter PD. Exercise and associated dietary extremes impact on gut microbial diversity. Gut. 2014 Dec;63(12):1913-20. doi: 10.1136/gutjnl-2013-306541. Epub 2014 Jun 9.
- Background: PubMed 23549027Lapthorne S, Pereira-Fantini PM, Fouhy F, Wilson G, Thomas SL, Dellios NL, Scurr M, O'Sullivan O, Ross RP, Stanton C, Fitzgerald GF, Cotter PD, Bines JE. Gut microbial diversity is reduced and is associated with colonic inflammation in a piglet model of short bowel syndrome. Gut Microbes. 2013 May-Jun;4(3):212-21. doi: 10.4161/gmic.24372. Epub 2013 Apr 2.
- Background: PubMed 18723164O'Mahony SM, Marchesi JR, Scully P, Codling C, Ceolho AM, Quigley EM, Cryan JF, Dinan TG. Early life stress alters behavior, immunity, and microbiota in rats: implications for irritable bowel syndrome and psychiatric illnesses. Biol Psychiatry. 2009 Feb 1;65(3):263-7. doi: 10.1016/j.biopsych.2008.06.026. Epub 2008 Aug 23.
- Background: PubMed 21844910DuPont AW, DuPont HL. The intestinal microbiota and chronic disorders of the gut. Nat Rev Gastroenterol Hepatol. 2011 Aug 16;8(9):523-31. doi: 10.1038/nrgastro.2011.133.
- Background: PubMed 1235985Melzack R. The McGill Pain Questionnaire: major properties and scoring methods. Pain. 1975 Sep;1(3):277-299. doi: 10.1016/0304-3959(75)90044-5.
- Background: PubMed 15983473Melzack R. The McGill pain questionnaire: from description to measurement. Anesthesiology. 2005 Jul;103(1):199-202. doi: 10.1097/00000542-200507000-00028.
- Background: PubMed 26563991Stalder T, Kirschbaum C, Kudielka BM, Adam EK, Pruessner JC, Wust S, Dockray S, Smyth N, Evans P, Hellhammer DH, Miller R, Wetherell MA, Lupien SJ, Clow A. Assessment of the cortisol awakening response: Expert consensus guidelines. Psychoneuroendocrinology. 2016 Jan;63:414-32. doi: 10.1016/j.psyneuen.2015.10.010. Epub 2015 Oct 20.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
George Shorten, Professor study chair
Professor of Anaesthesia and Intensive Care Medicine, Consultant Anaesthetist, University College Cork / Cork University Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Pain, Postoperative and Gastrointestinal Microbiome, run by Cork University Hospital at 2 sites in Ireland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Ireland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Association between gut microbiome α diversity and the magnitude of rebound pain (Numerical Rating Scale) (time frame: Perioperative period). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02998177, which also lists 11 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Aug 2017.