Characterization of Rebound Pain Following Peripheral Nerve Block and Its Association With Gut Microbiome Diversity
Condition: Pain, Postoperative; Gastrointestinal Microbiome
MeSH terms: Pain, Postoperative
Study type: Observational

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.
    

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.
    

Observational model: Case-Only
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        ASA I-II patients scheduled to undergo upper limb surgery under brachial plexus block will
        be recruited.
      
Biospecimen description: 
      Pre- and postoperative faecal samples and preoperative salivary samples are going to be
      taken.
    
Keywords: Postoperative pain; Rebound pain; Gut microbiome; Gut microbiota; Peripheral nerve block; Axillary brachial plexus block