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

Pain, Postoperative Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02998177
• Other study ID #: GMB-RP
• Status: Completed
• Phase: N/A
• First received: November 28, 2016
• Last updated: August 19, 2017
• Start date: November 2016
• Est. completion date: June 16, 2017

Study information

• Verified date: August 2017
• Source: Cork University Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical 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. 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: June 16, 2017
• Est. primary completion date: June 16, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Gastrointestinal Microbiome
• Pain, Postoperative

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Cork University Hospital

Country where clinical trial is conducted

Ireland, 

References & Publications (11)

Clarke 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. — View Citation

DuPont 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. Review. — View Citation

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. — View Citation

Hsiao 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. — View Citation

Lapthorne 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. — View Citation

Melzack R. The McGill pain questionnaire: from description to measurement. Anesthesiology. 2005 Jul;103(1):199-202. — View Citation

Melzack R. The McGill Pain Questionnaire: major properties and scoring methods. Pain. 1975 Sep;1(3):277-99. — View Citation

O'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. — View Citation

Stalder T, Kirschbaum C, Kudielka BM, Adam EK, Pruessner JC, Wüst 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. Review. — View Citation

Williams 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. — View Citation

Williams 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. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Association between gut microbiome a diversity and the magnitude of rebound pain (Numerical Rating Scale)		Perioperative period
Secondary	Association between gut microbiome a diversity and magnitude of postoperative pain (Numerical Rating Scale).		Perioperative period
Secondary	Association between gut microbiome a diversity and analgesic consumption (mg/24 hours).		Perioperative period
Secondary	Association between gut microbiome a diversity and salivary cortisol concentration (ng/ml).		Perioperative period
Secondary	Association between gut microbiome a diversity and Pain Perception Threshold (PPT, mAmp).		Perioperative period
Secondary	Association between gut microbiome constitution (a diversity) and incidence of persistent post-surgical pain.		Up to 4 weeks postoperatively
Secondary	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.		Up to 48 hours postoperatively