Effect of the Cannabinoid Agonist WIN 55,212-2 on Neuropathic and Visceral Pain Induced by a Non-Diarrheagenic Dose of the Antitumoral Drug 5-Fluorouracil in the Rat
5-fluorouracil (5-FU) is an antineoplastic drug used to treat colorectal cancer, but it causes, among other adverse effects, diarrhea and mucositis, as well as enteric neuropathy, as shown in experimental animals. It might also cause neuropathic pain and alterations in visceral sensitivity, but this...
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MDPI AG
2023-09-01
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| author | Gema Vera Laura López-Gómez Rocío Girón María Isabel Martín-Fontelles Kulmira Nurgali Raquel Abalo José Antonio Uranga |
| author_facet | Gema Vera Laura López-Gómez Rocío Girón María Isabel Martín-Fontelles Kulmira Nurgali Raquel Abalo José Antonio Uranga |
| author_sort | Gema Vera |
| collection | DOAJ |
| description | 5-fluorouracil (5-FU) is an antineoplastic drug used to treat colorectal cancer, but it causes, among other adverse effects, diarrhea and mucositis, as well as enteric neuropathy, as shown in experimental animals. It might also cause neuropathic pain and alterations in visceral sensitivity, but this has not been studied in either patients or experimental animals. Cannabinoids have antimotility and analgesic effects and may alleviate 5-FU-induced adverse effects. Our aim was to evaluate the effects of the cannabinoid agonist WIN 55,212-2 on neuropathic and visceral pain induced by a non-diarrheagenic dose of 5-FU. Male Wistar rats received a dose of 5-FU (150 mg/kg, ip) and gastrointestinal motility, colonic sensitivity, gut wall structure and tactile sensitivity were evaluated. WIN 55,212-2 (WIN) was administered to evaluate its effect on somatic (50–100 µg ipl; 1 mg/kg, ip) and visceral (1 mg/kg, ip) sensitivity. The cannabinoid tetrad was used to assess the central effects of WIN (1 mg/kg, ip). 5-FU decreased food intake and body weight gain, produced mucositis and thermal hyperalgesia, but these effects were reduced afterwards, and were not accompanied by diarrhea. Tactile mechanical allodynia was also evident and persisted for 15 days. Interestingly, it was alleviated by WIN. 5-FU tended to increase colonic sensitivity whereas WIN reduced the abdominal contractions induced by increasing intracolonic pressure in both control and 5-FU-treated animals. Importantly, the alleviating effects of WIN against those induced by 5-FU were not accompanied by any effect in the cannabinoid tetrad. The activation of the peripheral cannabinoid system may be useful to alleviate neuropathic and visceral pain associated with antitumoral treatment. |
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| language | English |
| last_indexed | 2024-03-10T21:44:13Z |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-f0e3eca6bbad4636ba6daf8ce696946e2023-11-19T14:26:27ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-09-0124191443010.3390/ijms241914430Effect of the Cannabinoid Agonist WIN 55,212-2 on Neuropathic and Visceral Pain Induced by a Non-Diarrheagenic Dose of the Antitumoral Drug 5-Fluorouracil in the RatGema Vera0Laura López-Gómez1Rocío Girón2María Isabel Martín-Fontelles3Kulmira Nurgali4Raquel Abalo5José Antonio Uranga6Department of Basic Health Sciences, Faculty of Health Sciences, University Rey Juan Carlos (URJC), 28922 Alcorcón, SpainDepartment of Basic Health Sciences, Faculty of Health Sciences, University Rey Juan Carlos (URJC), 28922 Alcorcón, SpainDepartment of Basic Health Sciences, Faculty of Health Sciences, University Rey Juan Carlos (URJC), 28922 Alcorcón, SpainDepartment of Basic Health Sciences, Faculty of Health Sciences, University Rey Juan Carlos (URJC), 28922 Alcorcón, SpainInstitute for Health and Sport, College of Health and Biomedicine, Victoria University, Melbourne, VIC 3011, AustraliaDepartment of Basic Health Sciences, Faculty of Health Sciences, University Rey Juan Carlos (URJC), 28922 Alcorcón, SpainDepartment of Basic Health Sciences, Faculty of Health Sciences, University Rey Juan Carlos (URJC), 28922 Alcorcón, Spain5-fluorouracil (5-FU) is an antineoplastic drug used to treat colorectal cancer, but it causes, among other adverse effects, diarrhea and mucositis, as well as enteric neuropathy, as shown in experimental animals. It might also cause neuropathic pain and alterations in visceral sensitivity, but this has not been studied in either patients or experimental animals. Cannabinoids have antimotility and analgesic effects and may alleviate 5-FU-induced adverse effects. Our aim was to evaluate the effects of the cannabinoid agonist WIN 55,212-2 on neuropathic and visceral pain induced by a non-diarrheagenic dose of 5-FU. Male Wistar rats received a dose of 5-FU (150 mg/kg, ip) and gastrointestinal motility, colonic sensitivity, gut wall structure and tactile sensitivity were evaluated. WIN 55,212-2 (WIN) was administered to evaluate its effect on somatic (50–100 µg ipl; 1 mg/kg, ip) and visceral (1 mg/kg, ip) sensitivity. The cannabinoid tetrad was used to assess the central effects of WIN (1 mg/kg, ip). 5-FU decreased food intake and body weight gain, produced mucositis and thermal hyperalgesia, but these effects were reduced afterwards, and were not accompanied by diarrhea. Tactile mechanical allodynia was also evident and persisted for 15 days. Interestingly, it was alleviated by WIN. 5-FU tended to increase colonic sensitivity whereas WIN reduced the abdominal contractions induced by increasing intracolonic pressure in both control and 5-FU-treated animals. Importantly, the alleviating effects of WIN against those induced by 5-FU were not accompanied by any effect in the cannabinoid tetrad. The activation of the peripheral cannabinoid system may be useful to alleviate neuropathic and visceral pain associated with antitumoral treatment.https://www.mdpi.com/1422-0067/24/19/14430cancer chemotherapycannabinoidchemotherapy-induced adverse effectsgastrointestinal motor functionperipheral neuropathyvisceral pain |
| spellingShingle | Gema Vera Laura López-Gómez Rocío Girón María Isabel Martín-Fontelles Kulmira Nurgali Raquel Abalo José Antonio Uranga Effect of the Cannabinoid Agonist WIN 55,212-2 on Neuropathic and Visceral Pain Induced by a Non-Diarrheagenic Dose of the Antitumoral Drug 5-Fluorouracil in the Rat International Journal of Molecular Sciences cancer chemotherapy cannabinoid chemotherapy-induced adverse effects gastrointestinal motor function peripheral neuropathy visceral pain |
| title | Effect of the Cannabinoid Agonist WIN 55,212-2 on Neuropathic and Visceral Pain Induced by a Non-Diarrheagenic Dose of the Antitumoral Drug 5-Fluorouracil in the Rat |
| title_full | Effect of the Cannabinoid Agonist WIN 55,212-2 on Neuropathic and Visceral Pain Induced by a Non-Diarrheagenic Dose of the Antitumoral Drug 5-Fluorouracil in the Rat |
| title_fullStr | Effect of the Cannabinoid Agonist WIN 55,212-2 on Neuropathic and Visceral Pain Induced by a Non-Diarrheagenic Dose of the Antitumoral Drug 5-Fluorouracil in the Rat |
| title_full_unstemmed | Effect of the Cannabinoid Agonist WIN 55,212-2 on Neuropathic and Visceral Pain Induced by a Non-Diarrheagenic Dose of the Antitumoral Drug 5-Fluorouracil in the Rat |
| title_short | Effect of the Cannabinoid Agonist WIN 55,212-2 on Neuropathic and Visceral Pain Induced by a Non-Diarrheagenic Dose of the Antitumoral Drug 5-Fluorouracil in the Rat |
| title_sort | effect of the cannabinoid agonist win 55 212 2 on neuropathic and visceral pain induced by a non diarrheagenic dose of the antitumoral drug 5 fluorouracil in the rat |
| topic | cancer chemotherapy cannabinoid chemotherapy-induced adverse effects gastrointestinal motor function peripheral neuropathy visceral pain |
| url | https://www.mdpi.com/1422-0067/24/19/14430 |
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