Key result
Experimental TNBS-induced colitis significantly decreased the pain threshold for mechanical allodynia and thermal hyperalgesia, reduced colonic expulsion time, and increased sympathetic autonomic activity.
Why the study?
Does subdiaphragmatic vagotomy exacerbate pain hypersensitivity and autonomic sympathovagal imbalance in a rat model of TNBS-induced colitis?
Does subdiaphragmatic vagotomy exacerbate pain hypersensitivity and autonomic sympathovagal imbalance in a rat model of TNBS-induced colitis?
In a rat model of TNBS-induced colitis, disruption of vagal innervation exacerbates pain hypersensitivity and autonomic sympathovagal imbalance, highlighting the vagus nerve's protective role in neuro-immune-cardiac interactions during intestinal inflammation.
May support vagal protection against colitis-induced hypersensitivity in rats; leaves open translation to human IBD neuromodulation.
Introduction: Pain hypersensitivity, abnormal motility and autonomic dysfunction contribute to functional symptoms of inflammatory bowel disease (IBD). Material and methods: The aim of this study was to assess: nociceptive thresholds for mechanical allodynia (MA) and thermal hyperalgesia (TH), intestinal motility (distal colonic transit and emptying), and cardiac autonomic neuropathy (indices of heart rate variability -HRV) in male Wistar rats with experimental trinitrobenzene sulfonic acid (TNBS) induced colitis. To identify a potential vagal contribution the bilateral subdiaphragmatic vagotomy (SDV) was performed. Results: Experimental colitis resulted in a significant decrease in pain threshold (MA 23.60 2.12, p < 0.001, TH 8.51 1.49, p < 0.001), reduced expulsion time (6.2 3.5, p < 0,01) and increase in the sympathetic autonomic activity (LFnu 32.54 21.16, p < 0.03). The animals with diminished vagal integrity presented with reduced gastrointestinal motility (39.8 25.1, p < 0.01) and a decrease in the parasympathetic high-frequency domain of HRV (HFnu 55.37 22.80, p < 0.002). The vagotomized rats with colitis showed the strongest nociceptive response (MA 22.46 3.02, p < 0.004; TH 7.99 1.12, p < 0.003) as well as significant changes in sympatho-vagal balance on HRV testing (LFnu 28.25 14.66, p < 0.04; HFnu 71.34 14.55, p < 0.04). Conclusions: The relationship between the cardiovascular and gastrointestinal system is modulated by neural, hormonal and inflammatory factors. This leads to dysregulation of the brain-gut interactions in the course of IBD. Sensitization and visceral-somatic convergence trigger pain hypersensitivity and autonomic sympathovagal imbalance. While integral vagal innervation impacts analgesic mechanisms via modulation of the immune response, SDV raises sympathetic activity and induces excessive hyperalgesia.
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Ciesielczyk et al. (2017) studied Inflammatory bowel disease (TNBS-induced colitis model) (n=40). TNBS-induced colitis vs. Saline enema (Control) was evaluated on Mechanical allodynia threshold (paw withdrawal threshold in grams) (p=<0.001). Experimental TNBS-induced colitis significantly decreased the pain threshold for mechanical allodynia and thermal hyperalgesia, reduced colonic expulsion time, and increased sympathetic autonomic activity.
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