kaolinite and Peripheral-Nervous-System-Diseases

Chemotherapy induces nausea/emesis and gastrointestinal dysmotility. Pica, the ingestion of non-nutritive substances, is considered as an indirect marker of nausea/emesis in non-vomiting species, like the rat. Cisplatin is the most emetogenic antitumoral drug. In the rat, acute cisplatin induces pica and gastric dysmotility in a temporally related manner, but the effects of chronic cisplatin are not well known. This study analyzed the effects of chronic cisplatin on pica and on gastrointestinal motor function in the rat, using radiographic, non-invasive methods.. Rats received saline or cisplatin (1-3 mg kg(-1), i.p.) once a week for four consecutive weeks. Serial X-rays were taken 0-8 h after administration of barium sulfate, which was given intragastrically immediately after the first and last cisplatin administrations and 1 week after treatment finalization. Pica (i.e., kaolin intake) was measured in isolated rats.. Cisplatin delayed gastric emptying and induced acute (during the 24 h following each administration) pica. Upon chronic administration, these effects were exacerbated. In addition, basal kaolin intake was enhanced (facilitated) and gastric distension induced. Delayed gastric emptying and gastric distension were not apparent 1 week after treatment, but basal kaolin intake was still elevated.. Whereas gastric dysmotility induced by cisplatin is parallel to the development of acute pica and might underlie facilitation of pica throughout chronic treatment, it does not explain its long-term maintenance. These findings should be taken into account in the search for new antiemetic strategies.

Topics: Animals; Antineoplastic Agents; Body Temperature; Cisplatin; Enteric Nervous System; Feeding Behavior; Gastric Emptying; Gastrointestinal Motility; Gastrointestinal Transit; Kaolin; Male; Motor Activity; Pain Measurement; Peripheral Nervous System Diseases; Pica; Rats; Rats, Wistar

Anorexia, nausea/emesis and peripheral sensorial neuropathy are frequent adverse effects associated with chemotherapy. Cannabinoids have been proposed to alleviate these effects, but their preventive properties in long-term experimental models have not been tested. This study was conducted to determine whether or not a cannabinoid agonist (WIN-55,212-2) can prevent anorexia, pica (an indirect marker of nausea in non-vomiting species, consisting of the ingestion of non-nutritive substances such as kaolin) and mechanical allodynia (a marker of peripheral neuropathy) induced by the antineoplastic drug cisplatin chronically administered. Isolated rats with free access to food and kaolin received either saline, cannabinoid vehicle, WIN-55,212-2 (1-2 mg kg(-1)), cisplatin (1-2 mg kg(-1)), or both drugs once per week for five consecutive weeks. Modifications in temperature, body weight gain, food and kaolin intake, and the threshold for mechanical allodynia were recorded. Additionally, the acute psychoactive effects of the cannabinoid (hypomotility, hypothermia, analgesia and catalepsia) were assayed by means of the cannabinoid tetrad. WIN 55,212-2 prevented the development of mechanical allodynia but not anorexia, pica and reduction in weight gain induced by chronic cisplatin. The effect of WIN 55,212-2 was evident even at a dose lacking activity in the cannabinoid tetrad. The preventive effect on cisplatin-induced mechanical allodynia exerted by the cannabinoid could be due to a neuroprotective role, as has been suggested for other conditions. The present results support the interest in the evaluation of cannabinoids for treatment of patients suffering or likely to suffer neuropathic pain.

Topics: Analgesics; Animals; Antidiarrheals; Antineoplastic Agents; Benzoxazines; Body Temperature; Body Weight; Cisplatin; Feeding Behavior; Kaolin; Male; Morpholines; Naphthalenes; Pain; Peripheral Nervous System Diseases; Pica; Rats; Rats, Wistar