Maternal separation affects the electrophysiological properties of Aδ-fibres and nociceptive behaviours in male and female mice.

AIM: Early life adverse effects have been associated with an increased risk of suffering pain syndromes in adulthood. Although animal models are of great importance to study modifications of pain sensitivity, up to date the results obtained are contradicting due to the varied methodologies used. Therefore, the aim of the present study was to characterise, as a whole, possible modifications in visceral and somatic nociceptive responses in male and female ICR mice, submitted to two different protocols of maternal separation (MS), and possible modifications in the electrophysiological properties of peripheral nociceptive Aδ-primary afferents. MAIN METHODS: Male and female mice were submitted to 3 or 4-8 hr of daily MS from postnatal day (PND) 2-17 and early weaned. On PND 67 von Frey, hot plate and writhing tests were performed. Afterwards electrophysiological recordings were carried out, using the in vitro skin-saphenous nerve preparation in males. KEY FINDINGS: The short separation protocol of MS did not modify nociceptive sensitivity; but when mice were separated from their dams for the long separation, mechanical pain thresholds were modified in male and female mice and visceral nociception was increased in female mice. Electrophysiological recordings showed that cutaneous Aδ-fibres were sensitised and their mechanotransduction properties were altered in both MS protocols. SIGNIFICANCE: Although MS increases the activity and the mechanosensitivity of cutaneous Aδ-afferent fibres at both short and long periods of separation, only the longer interval of time induces nociceptive sensitivity alterations during adulthood. These results highlight the possible influence of a stress free environment during childhood to reduce nociceptive alterations in adulthood.

Changes in the diet composition of fatty acids and fiber affect the lower gastrointestinal motility but have no impact on cardiovascular parameters: In vivo and in vitro studies.

BACKGROUND: Food and diet are central issues for proper functioning of the cardiovascular (CV) system and gastrointestinal (GI) tract. We hypothesize that different types of dietary FAs affect CV parameters as well as GI motor function and visceral sensitivity. METHODS: Male Wistar rats were fed with control diet (CTRL), diet supplemented with 7% soybean oil (SOY), SOY + 3.5% virgin coconut oil (COCO), and SOY + 3.5% evening primrose oil (EP) for 4 weeks. The content of insoluble fiber in CTRL was higher than in SOY, COCO, or EP. Body weight gain and food/water intake were measured. At day 28, biometric, biochemical, CV parameters, GI motor function (X-ray and colon bead expulsion test), and visceral sensitivity were evaluated. Changes in propulsive colonic activity were determined in vitro. The colon and adipose tissue were histologically studied; the number of mast cells (MCs) in the colon was calculated. RESULTS: SOY, COCO, and EP had increased body weight gain but decreased food intake vs CTRL. Water consumption, biometric, biochemical, and CV parameters were comparable between groups. SOY increased the sensitivity to colonic distention. All groups maintained regular propulsive neurogenic contractions; EP delayed colonic motility (P < 0.01). SOY, COCO, and EP displayed decreased size of the cecum, lower number and size of fecal pellets, and higher infiltration of MCs to the colon (P < 0.001). CONCLUSIONS AND INFERENCES: Dietary FAs supplementation and lower intake of insoluble fiber can induce changes in the motility of the lower GI tract, in vivo and in vitro, but CV function and visceral sensitivity are not generally affected.

Alterations of colonic sensitivity and gastric dysmotility after acute cisplatin and granisetron.

BACKGROUND: Cisplatin is a highly emetogenic antineoplastic drug and induces peripheral neuropathy when given in cycles. Granisetron, a 5-HT3 antagonist, is clinically used to prevent chemotherapy-induced nausea/emesis and abdominal pain in irritable bowel syndrome. The effects of cisplatin on visceral sensitivity and those of granisetron in the context of cancer chemotherapy are not well known. METHODS: Adult male Wistar rats received two intraperitoneal injections 30 minutes apart: granisetron (1 mg kg-1 )/vehicle and cisplatin (6 mg kg-1 )/vehicle. Thereafter, nausea-like behavior was measured as bedding intake for 4 hours, and gastric dysmotility was measured radiographically for 8 hours. Gastric weight and size were determined ex vivo and samples of the forestomach, corpus, ileum, and colon were obtained for histological analysis at 4 and 30 hours after cisplatin/vehicle. Visceral sensitivity was measured as abdominal contractions in response to mechanical intracolonic stimulation 2 hours after cisplatin/vehicle. KEY RESULTS: Cisplatin-induced bedding intake and gastric dysmotility, and granisetron blocked these effects, which occurred in the absence of frank mucositis. Visceral sensitivity was reduced to a similar extent by both drugs alone or in combination. CONCLUSIONS AND INFERENCES: Cisplatin-induced bedding intake and gastric dysmotility were blocked by granisetron, confirming the involvement of serotonin acting on 5-HT3 receptors. Unexpectedly, visceral sensitivity to colonic distension was reduced, to the same extent, by cisplatin, granisetron, and their combination, suggesting important mechanistic differences with nausea and gastric dysmotility that warrant further investigation.