Animal models of visceral pain and the role of the microbiome

Abstract

Visceral pain refers to pain arising from the internal organs and is distinctly different from the expression and mechanisms of somatic pain. Diseases and disorders with increased visceral pain are associated with significantly reduced quality of life and incur large financial costs due to medical visits and lost work productivity. In spite of the notable burden of illness associated with those disorders involving increased visceral pain, and some knowledge regarding etiology, few successful therapeutics have emerged, and thus increased attention to animal models of visceral hypersensitivity is warranted in order to elucidate new treatment opportunities. Altered microbiota-gut-brain (MGB) axis communication is central to the comorbid gastrointestinal/psychiatric diseases of which increased visceral (intestinal) sensitivity is a hallmark. This has led to a particular focus on intestinal microbiome disruption and its potential role in the etiology of heightened visceral pain. Here we provide a review of studies examining models of heightened visceral pain due to altered bidirectional communication of the MGB axis, many of which are conducted on a background of stress exposure. We discuss work in which the intestinal microbiota has either been directly manipulated (as with germ-free, antibiotic, and fecal microbial transplantation studies) or indirectly affected through early life or adult stress, inflammation, and infection. Animal models of visceral pain alterations with accompanying changes to the intestinal microbiome have the highest face and construct validity to the human condition and are the focus of the current review.

The Gut Microbial Bile Acid Modulation and Its Relevance to Digestive Health and Diseases

“… 119 , 120 A recent review of the role of microbiome in animal models of visceral pain provides an excellent summary. 121 …”

Electroacupuncture Relieves Visceral Hypersensitivity via Balancing PAR2 and PAR4 in the Descending Pain Modulatory System of Goats

“…Multiple animal models of VH were used to explore these mechanisms. Some studies reported that repeated CRD in rat neonates induces VH in adulthood [ 29 , 30 ]. Lee et al examined rats with water avoidance stress-induced colonic hypersensitivity [ 31 ].…”

Long‐lasting visceral hypersensitivity in a model of DSS‐induced colitis in rats

“…[5][6][7] Taking this into account, numerous animal models have been developed for the assessment of visceral sensitivity in normal conditions or in states of sensitization. A systematic review of these models is out of the scope of the present work and can be found [8][9][10][11] Several animal models of intestinal hypersensitivity have been developed based on the evidence that inflammation seems to be a pathophysiological component of inflammatory and functional GI disorders, as mentioned above. Overall, postinflammatory models have been based on the local administration (intracolonic enemas) of different active compounds (such as acetic acid, capsaicin, mustard oil, zymosan, trinitrobenzene sulfonic acid (TNBS)-or dinitrobenzene sulfonic acid (DNBS)) [12][13][14][15][16] or the experimental infection with biological agents (such as Trichinella spiralis, Nippostrongylus brasiliensis or Campylobacter species).…”

“…Taking this into account, numerous animal models have been developed for the assessment of visceral sensitivity in normal conditions or in states of sensitization. A systematic review of these models is out of the scope of the present work and can be found elsewhere [see as examples: Regmi and Shah (2020); Johnson et al (2020); West and McVey Neufeld (2021); Accarie and Vanuytsel (2020)] 8–11 . Several animal models of intestinal hypersensitivity have been developed based on the evidence that inflammation seems to be a pathophysiological component of inflammatory and functional GI disorders, as mentioned above.…”