Repeated Water Avoidance Stress Alters Mucosal Mast Cell Counts, Interleukin-1β Levels with Sex Differences in the Distal Colon of Wistar Rats

Abstract

Background/AimsThis study was aimed at evaluating differences in the effects of repeated water avoidance stress (rWAS) on colonic movement, mucosal mast cell counts, cytokine levels, and visceromotor response (VMR) to colorectal distension (CRD) in rats of both sexes. MethodsWistar rats were divided into stress and no-stress groups. Rats in the stress group were exposed to rWAS (1 hr/day) for 10 days. Mucosal mast cells were immunohistochemically stained with anti-mast cell tryptase antibody and counted. The colonic mucosal cytokine levels were measured with enzyme-linked immunosorbent assay. The VMR to CRD (visceral analgesia) was assessed by using a barostat and noninvasive manometry. ResultsThe mean number of fecal pellets in the rWAS group increased significantly as compared with that in the no-stress group in both sexes. After adjustment for body weight, the female rats had a significantly higher pellet output than the male rats. The mucosal mast cell count of the female rWAS group was higher than that of the male rWAS group (13.0 ± 0.9 vs 8.8 ± 0.6; P < 0.001). The colonic mucosal interleukin-1β level was also higher only in the female rats of the rWAS group than in those of the no-stress group. On days 10 and 11, a decrease in VMR to CRD was observed at 40 and 60 mmHg in both sexes of the rWAS group, without a sex-based difference. ConclusionsThe colonic response to stress appeared to be more sensitive in the female rats than in the male rats. However, stress-induced visceral analgesia had no sex-related difference and the underlying mechanism needs to be further evaluated.

Brain corticotropin‐releasing factor signaling: Involvement in acute stress‐induced visceral analgesia in male rats

“…Conversely, our recent studies, using a non‐invasive method of VMR recording based on manometry, highlighted the development of visceral analgesia in response to acute and/or repeated WAS in both mice and rats . Since then, other groups using WAS paired with CRD as a visceral painful stimulus have reproduced this visceral analgesic response in rats, using similar non‐invasive VMR recording or acute fixation of EMG electrodes on the external oblique muscles (30 minutes before CRD) . We and others also established that the visceral analgesia induced by acute and repeated WAS is opioid‐independent in male rats .…”

Ephrin‐B2 signaling in the spinal cord as a player in post‐inflammatory and stress‐induced visceral hypersensitivity

“…Interestingly, the expression level of some inflammatory markers ( IL‐1β, IL‐10, IL‐17, IFN‐γ, TNF‐α, and Ccl2 ) was upregulated and muscle thickness was increased in ephrin‐B2 cKO compared with WT mice (Figure A,C), suggesting that ephrin‐B2 from Na v 1.8 neurons may be involved in immune homeostasis. Additionally, although MS‐induced stress alters the fecal pellet output after each WAS session as well as the escape behavior compared to no handling, the stress response was similar between WT and cKO mice (Figure S2G,H).…”

“…Colonic compliance was studied at the end of each study protocol. Each mouse underwent graded distentions with air volumes at 20‐40‐60‐80 µL (each of 20‐second duration) delivered by a gastight syringe using a custom‐made balloon inserted in the colorectum, while monitoring and recording the corresponding colorectal pressure using Spike2 V.607 (Cambridge Electronic Design) and Philips CMS Patient Monitor System (M1109A/ M1041A) (Philips Medizin Systeme). Data presented in Figure S1A,B are expressed as delta from the minimum pressure achieved during the minimum distension (20 µL).…”

Repeated water avoidance stress induces visceral hypersensitivity: Role of interleukin‐1, interleukin‐6, and peripheral corticotropin‐releasing factor

“…There are several studies investigating the effects of repeated WAS on visceral sensation in rodents, and the majority of them demonstrated that repeated WAS induced visceral hypersensitivity . However, a few studies reported that it induced hyposensitivity or no change . The discrepancy of the results may be explained by the difference of animals, sex, or method measuring abdominal contractions induced by colonic distention, such as EMG and non‐invasive manometry …”

“…[7][8][9][10] However, a few studies reported that it induced hyposensitivity or no change. 24,25 The discrepancy of the results may be explained by the difference of animals, sex, or method measuring abdominal contractions induced by colonic distention, such as EMG and non-invasive manometry. 24,26 Our method detected the threshold of VMR by EMG with acute preparation, and we showed previously that acute single WAS induced visceral hyposensitivity using this method.…”