Background & Aims
Persistent post-surgical pain (PPSP) is a complication that occurs in a proportion of patients following surgical interventions(1). Consumption of a high fat, high sugar (HFHS) diet, is a modifiable risk factor for the development of many neuroinflammatory and neurodegenerative diseases(2). Current research suggests that specific gut microbiome components are important for optimal brain development and play important roles in homeostatic function. Moreover, recent studies have demonstrated that chronic pain states result in changes to the gut microbiome (3). While there is a link between HFHS diets and neurological function, the mechanisms driving this relationship have not been fully appreciated. Therefore, this study aimed to investigate how daily consumption of a HFHS diet modified the development of PPSP, neurodevelopment, and the microbiome. In addition, we examined the significant correlations between changes to the microbiome and neurodevelopment in animals with persistent pain.
Methods
Male and female Sprague Dawley rats were maintained on a standard or HFHS diet. Animals were further allocated to a sham or surgery condition on postnatal day (p) p35. The von Frey task was run at a chronic timepoint (p65-67) as a measure of PPSP, (mechanical nociceptive sensitivity). Between p68-72 all rats underwent in-vivo MRI for regional grey matter density and diffusivity analysis. At the endpoint (p73), fecal samples were used for downstream 16s rRNA sequencing. Spearman correlation analyses were performed between individual microbial abundance values and MRI diffusivity values from regions of interest that exhibited significant injury by diet interactions, to determine if specific bacterial species were associated with PSPP-induced brain changes.
Results
This study demonstrated that consumption of a HFHS diet exacerbated PPSP in adolescents. This mechanical hypersensitivity was associated with changes in brain volume and connectivity, and importantly these functional changes in neuroplasticity were correlated with modifications to the microbiome. Consumption of the HFHS diet reduced overall brain volume, including reductions in grey and white matter volumes. The loss of brain volume was associated with increased white and grey matter density. The HFHS diet interacted with the surgical intervention to modify diffusivity in the lateral parabrachial nucleus, amygdala, hypothalamus, cingulate cortex, caudate/putamen, prefrontal cortex, and the primary motor cortex. Spearman’s correlational analyses identified positive correlations between bacterial taxa and changes in diffusivity for animals that consumed the HFHS diet, within the caudate putamen, right primary motor cortex, hypothalamus, and cingulate cortex.
Conclusions
These findings demonstrate that premorbid characteristics and habits can influence the development of PPSP and advances understanding of the contribution that the microbiome has on brain development and function. Given that the HFHS diet exacerbated PPSP and induced significant changes to the microbiome as well as brain structure and function, there is promise that dietary interventions and biotic supplements could prevent its onset or reduce the risk for the manifestation of persistent pain in adolescents.
References
1.Kehlet H, Jensen T, Woolf C. Persistent postsurgical pain: risk factors and prevention. Lancet 2006;367:1618-25.
2.Popa-Wagner A, Dumitrascu D, Capitanescu B, Petcu E, Surugiu R, Fang W, et al. Dietary habits, lifestyle factors and neurodegenerative diseases. Neural Regeneration Research. 2020;15(3):394-400.
3 .Salberg S, MacCowan M, Yamakawa G, Beveridge J, Noel M, Marsland B, et al. Gut instinct: Sex differences in the microbiome modulate adolescent nociception following maternal separation in rats. Developmental Neurobiology. 2023;83:219-23.
4. Percie du Sert N, Hurst V, Ahluwalia A, Alam S, Avey MT, Baker M, et al. The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research. Journal of Cerebral Blood Flow & Metabolism. 2020;40(9):1769-77.
Presenting Author
Richelle Mychasiuk
Poster Authors
Richelle Mychasiuk
PhD
Monash University
Lead Author
Sabrina Salberg
Monash University
Lead Author
Matthew Macowan
Lead Author
Angela Doshen
Lead Author
Glenn Yamakawa (PhD)
Lead Author
Marissa Sgro (PhD)
Lead Author
Benjamin Marsland
Lead Author
Luke Henderson
PhD
The University of Sydney
Lead Author
Topics
- Mechanisms: Biological-Molecular and Cell Biology