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-HT 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 )/vehicle and cisplatin (6 mg kg )/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-HT 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.