Differential Effectiveness of Clinically-Relevant Analgesics in a Rat Model of Chemotherapy-Induced Mucositis
Chemotherapy-induced intestinal mucositis is characterized by pain and a pro-inflammatory tissue response. Rat models are frequently used in mucositis disease investigations yet little is known about the presence of pain in these animals, the ability of analgesics to ameliorate the condition, or the...
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| description | Chemotherapy-induced intestinal mucositis is characterized by pain and a pro-inflammatory tissue response. Rat models are frequently used in mucositis disease investigations yet little is known about the presence of pain in these animals, the ability of analgesics to ameliorate the condition, or the effect that analgesic administration may have on study outcomes. This study investigated different classes of analgesics with the aim of determining their analgesic effects and impact on research outcomes of interest in a rat model of mucositis. Female DA rats were allocated to 8 groups to include saline and chemotherapy controls (n = 8). Analgesics included opioid derivatives (buprenorphine; 0.05mg/kg and tramadol 12.5mg/kg) and NSAID (carprofen; 15mg/kg) in combination with either saline or 5-Fluorouracil (5-FU; 150mg/kg). Research outcome measures included daily clinical parameters, pain score and gut histology. Myeloperoxidase assay was performed to determine gut inflammation. At the dosages employed, all agents had an analgesic effect based on behavioural pain scores. Jejunal myeloperoxidase activity was significantly reduced by buprenorphine and tramadol in comparison to 5-FU control animals (53%, p = 0.0004 and 58%, p = 0.0001). Carprofen had no ameliorating effect on myeloperoxidase levels. None of the agents reduced the histological damage caused by 5-FU administration although tramadol tended to increase villus length even when administered to healthy animals. These data provide evidence that carprofen offers potential as an analgesic in this animal model due to its pain-relieving efficacy and minimal effect on measured parameters. This study also supports further investigation into the mechanism and utility of opioid agents in the treatment of chemotherapy-induced mucositis. |
| doi_str_mv | 10.1371/journal.pone.0158851 |
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Rat models are frequently used in mucositis disease investigations yet little is known about the presence of pain in these animals, the ability of analgesics to ameliorate the condition, or the effect that analgesic administration may have on study outcomes. This study investigated different classes of analgesics with the aim of determining their analgesic effects and impact on research outcomes of interest in a rat model of mucositis. Female DA rats were allocated to 8 groups to include saline and chemotherapy controls (n = 8). Analgesics included opioid derivatives (buprenorphine; 0.05mg/kg and tramadol 12.5mg/kg) and NSAID (carprofen; 15mg/kg) in combination with either saline or 5-Fluorouracil (5-FU; 150mg/kg). Research outcome measures included daily clinical parameters, pain score and gut histology. Myeloperoxidase assay was performed to determine gut inflammation. At the dosages employed, all agents had an analgesic effect based on behavioural pain scores. Jejunal myeloperoxidase activity was significantly reduced by buprenorphine and tramadol in comparison to 5-FU control animals (53%, p = 0.0004 and 58%, p = 0.0001). Carprofen had no ameliorating effect on myeloperoxidase levels. None of the agents reduced the histological damage caused by 5-FU administration although tramadol tended to increase villus length even when administered to healthy animals. These data provide evidence that carprofen offers potential as an analgesic in this animal model due to its pain-relieving efficacy and minimal effect on measured parameters. This study also supports further investigation into the mechanism and utility of opioid agents in the treatment of chemotherapy-induced mucositis.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0158851</identifier><identifier>PMID: 27463799</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>5-Fluorouracil ; Analgesics ; Analgesics - pharmacology ; Analgesics - therapeutic use ; Animal models ; Animals ; Antineoplastic Agents - adverse effects ; Behavior, Animal - drug effects ; Biology and Life Sciences ; Buprenorphine ; Cancer therapies ; Chemotherapy ; Complications and side effects ; Cytotoxicity ; Diagnosis ; Digestive system ; Digestive tract ; Disease Models, Animal ; Dosage and administration ; Drug therapy ; Female ; Gastrointestinal tract ; Histology ; Immune system ; Inflammation ; Intestinal Mucosa - drug effects ; Intestinal Mucosa - enzymology ; Intestinal Mucosa - pathology ; Intestine ; Laboratory animals ; Mathematical models ; Medicine and Health Sciences ; Metabolism ; Mucositis ; Mucositis - chemically induced ; Mucositis - drug therapy ; Mucositis - pathology ; Narcotics ; Opioids ; Pain ; Peroxidase ; Peroxidase - metabolism ; Rats ; Risk factors ; Rodents ; Tramadol ; Villus</subject><ispartof>PloS one, 2016-07, Vol.11 (7), p.e0158851-e0158851</ispartof><rights>COPYRIGHT 2016 Public Library of Science</rights><rights>2016 Whittaker et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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Rat models are frequently used in mucositis disease investigations yet little is known about the presence of pain in these animals, the ability of analgesics to ameliorate the condition, or the effect that analgesic administration may have on study outcomes. This study investigated different classes of analgesics with the aim of determining their analgesic effects and impact on research outcomes of interest in a rat model of mucositis. Female DA rats were allocated to 8 groups to include saline and chemotherapy controls (n = 8). Analgesics included opioid derivatives (buprenorphine; 0.05mg/kg and tramadol 12.5mg/kg) and NSAID (carprofen; 15mg/kg) in combination with either saline or 5-Fluorouracil (5-FU; 150mg/kg). Research outcome measures included daily clinical parameters, pain score and gut histology. Myeloperoxidase assay was performed to determine gut inflammation. At the dosages employed, all agents had an analgesic effect based on behavioural pain scores. Jejunal myeloperoxidase activity was significantly reduced by buprenorphine and tramadol in comparison to 5-FU control animals (53%, p = 0.0004 and 58%, p = 0.0001). Carprofen had no ameliorating effect on myeloperoxidase levels. None of the agents reduced the histological damage caused by 5-FU administration although tramadol tended to increase villus length even when administered to healthy animals. These data provide evidence that carprofen offers potential as an analgesic in this animal model due to its pain-relieving efficacy and minimal effect on measured parameters. This study also supports further investigation into the mechanism and utility of opioid agents in the treatment of chemotherapy-induced mucositis.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>27463799</pmid><doi>10.1371/journal.pone.0158851</doi><tpages>e0158851</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | PloS one, 2016-07, Vol.11 (7), p.e0158851-e0158851 |
| issn | 1932-6203 1932-6203 |
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| subjects | 5-Fluorouracil Analgesics Analgesics - pharmacology Analgesics - therapeutic use Animal models Animals Antineoplastic Agents - adverse effects Behavior, Animal - drug effects Biology and Life Sciences Buprenorphine Cancer therapies Chemotherapy Complications and side effects Cytotoxicity Diagnosis Digestive system Digestive tract Disease Models, Animal Dosage and administration Drug therapy Female Gastrointestinal tract Histology Immune system Inflammation Intestinal Mucosa - drug effects Intestinal Mucosa - enzymology Intestinal Mucosa - pathology Intestine Laboratory animals Mathematical models Medicine and Health Sciences Metabolism Mucositis Mucositis - chemically induced Mucositis - drug therapy Mucositis - pathology Narcotics Opioids Pain Peroxidase Peroxidase - metabolism Rats Risk factors Rodents Tramadol Villus |
| title | Differential Effectiveness of Clinically-Relevant Analgesics in a Rat Model of Chemotherapy-Induced Mucositis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-30T12%3A24%3A46IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Differential%20Effectiveness%20of%20Clinically-Relevant%20Analgesics%20in%20a%20Rat%20Model%20of%20Chemotherapy-Induced%20Mucositis&rft.jtitle=PloS%20one&rft.au=Whittaker,%20Alexandra%20L&rft.date=2016-07-27&rft.volume=11&rft.issue=7&rft.spage=e0158851&rft.epage=e0158851&rft.pages=e0158851-e0158851&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0158851&rft_dat=%3Cgale_plos_%3EA459324659%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1807273011&rft_id=info:pmid/27463799&rft_galeid=A459324659&rft_doaj_id=oai_doaj_org_article_841c927295064151840e336d519d2111&rfr_iscdi=true |