Pain, Postoperative Clinical Trial
Official title:
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.
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