Is there a reasonable excuse for not providing post-operative analgesia when using animal models of peripheral neuropathic pain for research purposes?
The induction of neuropathic pain-like behaviors in rodents often requires surgical intervention. This engages acute nociceptive signaling events that contribute to pain and stress post-operatively that from a welfare perspective demands peri-operative analgesic treatment. However, a large number of...
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description | The induction of neuropathic pain-like behaviors in rodents often requires surgical intervention. This engages acute nociceptive signaling events that contribute to pain and stress post-operatively that from a welfare perspective demands peri-operative analgesic treatment. However, a large number of researchers avoid providing such care based largely on anecdotal opinions that it might interfere with model pathophysiology in the longer term.
To investigate effects of various peri-operative analgesic regimens encapsulating different mechanisms and duration of action, on the development of post-operative stress/welfare and pain-like behaviors in the Spared Nerve Injury (SNI)-model of neuropathic pain.
Starting on the day of surgery, male Sprague-Dawley rats were administered either vehicle (s.c.), carprofen (5.0mg/kg, s.c.), buprenorphine (0.1mg/kg s.c. or 1.0mg/kg p.o. in Nutella®), lidocaine/bupivacaine mixture (local irrigation) or a combination of all analgesics, with coverage from a single administration, and up to 72 hours. Post-operative stress and recovery were assessed using welfare parameters, bodyweight, food-consumption, and fecal corticosterone, and hindpaw mechanical allodynia was tested for assessing development of neuropathic pain for 28 days.
None of the analgesic regimes compromised the development of mechanical allodynia. Unexpectedly, the combined treatment with 0.1mg/kg s.c. buprenorphine and carprofen for 72 hours and local irrigation with lidocaine/bupivacaine, caused severe adverse effects with peritonitis. This was not observed when the combination included a lower dose of buprenorphine (0.05mg/kg, s.c.), or when buprenorphine was administered alone (0.1mg/kg s.c. or 1.0mg/kg p.o.) for 72 hours. An elevated rate of wound dehiscence was observed especially in the combined treatment groups, underlining the need for balanced analgesia. Repeated buprenorphine injections had positive effects on body weight the first day after surgery, but depressive effects on food intake and body weight later during the first week.
Post-operative analgesia does not appear to affect established neuropathic hypersensitivity outcome in the SNI model. |
doi_str_mv | 10.1371/journal.pone.0188113 |
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To investigate effects of various peri-operative analgesic regimens encapsulating different mechanisms and duration of action, on the development of post-operative stress/welfare and pain-like behaviors in the Spared Nerve Injury (SNI)-model of neuropathic pain.
Starting on the day of surgery, male Sprague-Dawley rats were administered either vehicle (s.c.), carprofen (5.0mg/kg, s.c.), buprenorphine (0.1mg/kg s.c. or 1.0mg/kg p.o. in Nutella®), lidocaine/bupivacaine mixture (local irrigation) or a combination of all analgesics, with coverage from a single administration, and up to 72 hours. Post-operative stress and recovery were assessed using welfare parameters, bodyweight, food-consumption, and fecal corticosterone, and hindpaw mechanical allodynia was tested for assessing development of neuropathic pain for 28 days.
None of the analgesic regimes compromised the development of mechanical allodynia. Unexpectedly, the combined treatment with 0.1mg/kg s.c. buprenorphine and carprofen for 72 hours and local irrigation with lidocaine/bupivacaine, caused severe adverse effects with peritonitis. This was not observed when the combination included a lower dose of buprenorphine (0.05mg/kg, s.c.), or when buprenorphine was administered alone (0.1mg/kg s.c. or 1.0mg/kg p.o.) for 72 hours. An elevated rate of wound dehiscence was observed especially in the combined treatment groups, underlining the need for balanced analgesia. Repeated buprenorphine injections had positive effects on body weight the first day after surgery, but depressive effects on food intake and body weight later during the first week.
Post-operative analgesia does not appear to affect established neuropathic hypersensitivity outcome in the SNI model.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0188113</identifier><identifier>PMID: 29166664</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Analgesia ; Analgesics ; Anesthesia ; Animal models ; Animals ; Biology and Life Sciences ; Biomedical Research ; Biometrics ; Body Weight ; Bupivacaine ; Buprenorphine ; Combined treatment ; Corticosterone ; Dehiscence ; Development and progression ; Disease Models, Animal ; Drug therapy ; Feces ; Feeding Behavior ; Food consumption ; Food intake ; Fuel consumption ; Hyperalgesia - drug therapy ; Hypersensitivity ; Irrigation ; Laboratory animals ; Lidocaine ; Male ; Medicine and Health Sciences ; Metabolome ; Methods ; Narcotics ; Nerve Tissue - injuries ; Nerve Tissue - pathology ; Nerve Tissue - surgery ; Neuralgia - drug therapy ; Neurodegeneration ; Neuropathy ; Pain ; Pain perception ; Pain, Postoperative ; Pain, Postoperative - drug therapy ; Peripheral neuropathy ; Peritonitis ; Physiology ; Rats ; Rats, Sprague-Dawley ; Rodents ; Signaling ; Stress ; Stresses ; Studies ; Surgery ; Trauma ; Wounds</subject><ispartof>PloS one, 2017-11, Vol.12 (11), p.e0188113-e0188113</ispartof><rights>COPYRIGHT 2017 Public Library of Science</rights><rights>2017 Hestehave 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. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2017 Hestehave et al 2017 Hestehave et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c585t-ea6122c7c27a6e5b8126f355ccd13fe731b20bfe5b8d0084728263d83fbb65f23</citedby><cites>FETCH-LOGICAL-c585t-ea6122c7c27a6e5b8126f355ccd13fe731b20bfe5b8d0084728263d83fbb65f23</cites><orcidid>0000-0002-1837-521X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5699849/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5699849/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79569,79570</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29166664$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hestehave, Sara</creatorcontrib><creatorcontrib>Munro, Gordon</creatorcontrib><creatorcontrib>Christensen, Rie</creatorcontrib><creatorcontrib>Brønnum Pedersen, Tina</creatorcontrib><creatorcontrib>Arvastson, Lars</creatorcontrib><creatorcontrib>Hougaard, Philip</creatorcontrib><creatorcontrib>Abelson, Klas S P</creatorcontrib><title>Is there a reasonable excuse for not providing post-operative analgesia when using animal models of peripheral neuropathic pain for research purposes?</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The induction of neuropathic pain-like behaviors in rodents often requires surgical intervention. This engages acute nociceptive signaling events that contribute to pain and stress post-operatively that from a welfare perspective demands peri-operative analgesic treatment. However, a large number of researchers avoid providing such care based largely on anecdotal opinions that it might interfere with model pathophysiology in the longer term.
To investigate effects of various peri-operative analgesic regimens encapsulating different mechanisms and duration of action, on the development of post-operative stress/welfare and pain-like behaviors in the Spared Nerve Injury (SNI)-model of neuropathic pain.
Starting on the day of surgery, male Sprague-Dawley rats were administered either vehicle (s.c.), carprofen (5.0mg/kg, s.c.), buprenorphine (0.1mg/kg s.c. or 1.0mg/kg p.o. in Nutella®), lidocaine/bupivacaine mixture (local irrigation) or a combination of all analgesics, with coverage from a single administration, and up to 72 hours. Post-operative stress and recovery were assessed using welfare parameters, bodyweight, food-consumption, and fecal corticosterone, and hindpaw mechanical allodynia was tested for assessing development of neuropathic pain for 28 days.
None of the analgesic regimes compromised the development of mechanical allodynia. Unexpectedly, the combined treatment with 0.1mg/kg s.c. buprenorphine and carprofen for 72 hours and local irrigation with lidocaine/bupivacaine, caused severe adverse effects with peritonitis. This was not observed when the combination included a lower dose of buprenorphine (0.05mg/kg, s.c.), or when buprenorphine was administered alone (0.1mg/kg s.c. or 1.0mg/kg p.o.) for 72 hours. An elevated rate of wound dehiscence was observed especially in the combined treatment groups, underlining the need for balanced analgesia. Repeated buprenorphine injections had positive effects on body weight the first day after surgery, but depressive effects on food intake and body weight later during the first week.
Post-operative analgesia does not appear to affect established neuropathic hypersensitivity outcome in the SNI model.</description><subject>Analgesia</subject><subject>Analgesics</subject><subject>Anesthesia</subject><subject>Animal models</subject><subject>Animals</subject><subject>Biology and Life Sciences</subject><subject>Biomedical Research</subject><subject>Biometrics</subject><subject>Body Weight</subject><subject>Bupivacaine</subject><subject>Buprenorphine</subject><subject>Combined treatment</subject><subject>Corticosterone</subject><subject>Dehiscence</subject><subject>Development and progression</subject><subject>Disease Models, Animal</subject><subject>Drug therapy</subject><subject>Feces</subject><subject>Feeding Behavior</subject><subject>Food consumption</subject><subject>Food intake</subject><subject>Fuel consumption</subject><subject>Hyperalgesia - drug therapy</subject><subject>Hypersensitivity</subject><subject>Irrigation</subject><subject>Laboratory animals</subject><subject>Lidocaine</subject><subject>Male</subject><subject>Medicine and Health Sciences</subject><subject>Metabolome</subject><subject>Methods</subject><subject>Narcotics</subject><subject>Nerve Tissue - injuries</subject><subject>Nerve Tissue - pathology</subject><subject>Nerve Tissue - surgery</subject><subject>Neuralgia - drug therapy</subject><subject>Neurodegeneration</subject><subject>Neuropathy</subject><subject>Pain</subject><subject>Pain perception</subject><subject>Pain, Postoperative</subject><subject>Pain, Postoperative - drug therapy</subject><subject>Peripheral neuropathy</subject><subject>Peritonitis</subject><subject>Physiology</subject><subject>Rats</subject><subject>Rats, 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there a reasonable excuse for not providing post-operative analgesia when using animal models of peripheral neuropathic pain for research purposes?</title><author>Hestehave, Sara ; Munro, Gordon ; Christensen, Rie ; Brønnum Pedersen, Tina ; Arvastson, Lars ; Hougaard, Philip ; Abelson, Klas S P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c585t-ea6122c7c27a6e5b8126f355ccd13fe731b20bfe5b8d0084728263d83fbb65f23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Analgesia</topic><topic>Analgesics</topic><topic>Anesthesia</topic><topic>Animal models</topic><topic>Animals</topic><topic>Biology and Life Sciences</topic><topic>Biomedical Research</topic><topic>Biometrics</topic><topic>Body Weight</topic><topic>Bupivacaine</topic><topic>Buprenorphine</topic><topic>Combined treatment</topic><topic>Corticosterone</topic><topic>Dehiscence</topic><topic>Development and 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purposes?</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2017-11-22</date><risdate>2017</risdate><volume>12</volume><issue>11</issue><spage>e0188113</spage><epage>e0188113</epage><pages>e0188113-e0188113</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The induction of neuropathic pain-like behaviors in rodents often requires surgical intervention. This engages acute nociceptive signaling events that contribute to pain and stress post-operatively that from a welfare perspective demands peri-operative analgesic treatment. However, a large number of researchers avoid providing such care based largely on anecdotal opinions that it might interfere with model pathophysiology in the longer term.
To investigate effects of various peri-operative analgesic regimens encapsulating different mechanisms and duration of action, on the development of post-operative stress/welfare and pain-like behaviors in the Spared Nerve Injury (SNI)-model of neuropathic pain.
Starting on the day of surgery, male Sprague-Dawley rats were administered either vehicle (s.c.), carprofen (5.0mg/kg, s.c.), buprenorphine (0.1mg/kg s.c. or 1.0mg/kg p.o. in Nutella®), lidocaine/bupivacaine mixture (local irrigation) or a combination of all analgesics, with coverage from a single administration, and up to 72 hours. Post-operative stress and recovery were assessed using welfare parameters, bodyweight, food-consumption, and fecal corticosterone, and hindpaw mechanical allodynia was tested for assessing development of neuropathic pain for 28 days.
None of the analgesic regimes compromised the development of mechanical allodynia. Unexpectedly, the combined treatment with 0.1mg/kg s.c. buprenorphine and carprofen for 72 hours and local irrigation with lidocaine/bupivacaine, caused severe adverse effects with peritonitis. This was not observed when the combination included a lower dose of buprenorphine (0.05mg/kg, s.c.), or when buprenorphine was administered alone (0.1mg/kg s.c. or 1.0mg/kg p.o.) for 72 hours. An elevated rate of wound dehiscence was observed especially in the combined treatment groups, underlining the need for balanced analgesia. Repeated buprenorphine injections had positive effects on body weight the first day after surgery, but depressive effects on food intake and body weight later during the first week.
Post-operative analgesia does not appear to affect established neuropathic hypersensitivity outcome in the SNI model.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>29166664</pmid><doi>10.1371/journal.pone.0188113</doi><orcidid>https://orcid.org/0000-0002-1837-521X</orcidid><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1932-6203 |
ispartof | PloS one, 2017-11, Vol.12 (11), p.e0188113-e0188113 |
issn | 1932-6203 1932-6203 |
language | eng |
recordid | cdi_plos_journals_1967374738 |
source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
subjects | Analgesia Analgesics Anesthesia Animal models Animals Biology and Life Sciences Biomedical Research Biometrics Body Weight Bupivacaine Buprenorphine Combined treatment Corticosterone Dehiscence Development and progression Disease Models, Animal Drug therapy Feces Feeding Behavior Food consumption Food intake Fuel consumption Hyperalgesia - drug therapy Hypersensitivity Irrigation Laboratory animals Lidocaine Male Medicine and Health Sciences Metabolome Methods Narcotics Nerve Tissue - injuries Nerve Tissue - pathology Nerve Tissue - surgery Neuralgia - drug therapy Neurodegeneration Neuropathy Pain Pain perception Pain, Postoperative Pain, Postoperative - drug therapy Peripheral neuropathy Peritonitis Physiology Rats Rats, Sprague-Dawley Rodents Signaling Stress Stresses Studies Surgery Trauma Wounds |
title | Is there a reasonable excuse for not providing post-operative analgesia when using animal models of peripheral neuropathic pain for research purposes? |
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