Altered sympathovagal balance and pain hypersensitivity in TNBS-induced colitis

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.