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

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.

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.

Eligibility Criteria:
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