title: Analgesic Activity of Tramadol and Buprenorphine after Voluntary Ingestion by Rats (Rattus norvegicus).
abstract: Effective pain management for rats and mice is crucial due to the continuing increase in the use of these species in biomedical research. Here we used a recently validated operant orofacial pain assay to determine dose-response curves for buprenorphine and tramadol when mixed in nut paste and administered to male and female rats. Statistically significant analgesic doses of tramadol in nut paste included doses of 20, 30, and 40 mg/kg for female rats but only 40 mg/kg for male rats. For male rats receiving buprenorphine mixed in nut paste, a significant analgesic response was observed at 0.5 and 0.6 mg/kg. None of the doses tested produced a significant analgesic response in female rats. Our results indicate that at the doses tested, tramadol and buprenorphine produced an analgesic response in male rats. In female rats, tramadol shows a higher analgesic effect than buprenorphine. The analgesic effects observed 60 min after administration of the statistically significant oral doses of both drugs were similar to the analgesic effects of 0.03 mg/kg subcutaneous buprenorphine 30 min after administration. The method of voluntary ingestion could be effective, is easy to use, and would minimize stress to the rats during the immediate postoperative period.
authors.affiliation: Animal Care Services, University of Florida, Gainesville, Florida.
authors.forename: Bryan F
authors.initials: BF
authors.lastname: Taylor
authors.affiliation: Animal Care Services, University of Florida, Gainesville, Florida;, Email: hramir@ufl.edu.
authors.forename: Harvey E
authors.initials: HE
authors.lastname: Ramirez
authors.affiliation: Animal Care Services, University of Florida, Gainesville, Florida.
authors.forename: August H
authors.initials: AH
authors.lastname: Battles
authors.affiliation: Animal Care Services, University of Florida, Gainesville, Florida.
authors.forename: Karl A
authors.initials: KA
authors.lastname: Andrutis
authors.affiliation: Department of Orthodontics, University of Florida, Gainesville, Florida.
authors.forename: John K
authors.initials: JK
authors.lastname: Neubert
mesh_terms: D000284:Administration, Oral; D000700:Analgesics; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002047:Buprenorphine / Q000008:administration & dosage / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects; D005260:Female; D007756:Laboratory Animal Science; D008297:Male; D011184:Postoperative Period; D051381:Rats; D014147:Tramadol / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000700:Analgesics; D000701:Analgesics, Opioid; D014147:Tramadol; D002047:Buprenorphine
references.citation: Br J Clin Pharmacol. 1989 Dec;28(6):621-8
references.pmid: 2692684
references.citation: J Pharmacol Exp Ther. 1992 Jan;260(1):275-85
references.pmid: 1309873
references.citation: Pharmacol Biochem Behav. 1996 Aug;54(4):693-7
references.pmid: 8853191
references.citation: Pharmacol Biochem Behav. 1997 Mar;56(3):341-5
references.pmid: 9077567
references.citation: Lab Anim Sci. 1997 Jun;47(3):300-3
references.pmid: 9241634
references.citation: Nature. 1997 Oct 23;389(6653):816-24
references.pmid: 9349813
references.citation: Braz J Med Biol Res. 1997 Aug;30(8):981-4
references.pmid: 9361728
references.citation: Toxicol Lett. 1998 Mar 16;95(1):63-71
references.pmid: 9650647
references.citation: Contemp Top Lab Anim Sci. 2004 Nov;43(6):42-51
references.pmid: 15669134
references.citation: Anesth Analg. 2005 Mar;100(3):774-80, table of contents
references.pmid: 15728067
references.citation: Anesth Analg. 2005 May;100(5):1400-5, table of contents
references.pmid: 15845694
references.citation: Pain. 2005 Jun;115(3):296-307
references.pmid: 15911156
references.citation: Psychopharmacology (Berl). 2005 Jun;180(1):84-94
references.pmid: 15696324
references.citation: Contemp Top Lab Anim Sci. 2003 Mar;42(2):20-5
references.pmid: 19757620
references.citation: Am J Vet Res. 2009 Dec;70(12):1465-70
references.pmid: 19951117
references.citation: In Vivo. 2010 Mar-Apr;24(2):131-5
references.pmid: 20363983
references.citation: Horm Behav. 2010 Jun;58(1):72-81
references.pmid: 19786031
references.citation: J Am Assoc Lab Anim Sci. 2010 May;49(3):335-43
references.pmid: 20587166
references.citation: Shock. 2010 Sep;34(3):250-60
references.pmid: 20803785
references.citation: Lab Anim. 2010 Oct;44(4):337-43
references.pmid: 20837556
references.citation: In Vivo. 2010 Sep-Oct;24(5):641-6
references.pmid: 20952727
references.citation: Lab Anim (NY). 2010 Nov;39(11):342-51
references.pmid: 20962760
references.citation: Pain Pract. 2010 Sep-Oct;10(5):428-50
references.pmid: 20492579
references.citation: Behav Brain Res. 2011 Jan 20;216(2):723-5
references.pmid: 20797411
references.citation: J Pharmacol Sci. 2011;115(3):421-4
references.pmid: 21372504
references.citation: Eur J Clin Pharmacol. 2011 Sep;67(9):899-908
references.pmid: 21394525
references.citation: Mol Pain. 2011;7:55
references.pmid: 21801409
references.citation: J Orofac Pain. 2011 Fall;25(4):354-63
references.pmid: 22247931
references.citation: J Am Assoc Lab Anim Sci. 2012 Jan;51(1):42-9
references.pmid: 22330867
references.citation: Lab Anim. 2012 Oct;46(4):349-51
references.pmid: 22969145
references.citation: Trends Pharmacol Sci. 2012 Dec;33(12):646-55
references.pmid: 23068431
references.citation: J Vis Exp. 2013;(76):e50336
references.pmid: 23792907
references.citation: J Am Assoc Lab Anim Sci. 2013 Sep;52(5):553-9
references.pmid: 24041210
references.citation: J Am Assoc Lab Anim Sci. 2014 Mar;53(2):193-7
references.pmid: 24602547
references.citation: Pain. 2014 Dec;155(12):2534-44
references.pmid: 25239074
references.citation: J Am Assoc Lab Anim Sci. 2015 Jul;54(4):426-32
references.pmid: 26224444
references.citation: Pharmacol Biochem Behav. 2000 Jan 1;65(1):97-104
references.pmid: 10638642
references.citation: Neurosci Biobehav Rev. 2000 May;24(3):375-89
references.pmid: 10781697
references.citation: Anesthesiology. 2000 Aug;93(2):539-47
references.pmid: 10910505
references.citation: Psychopharmacology (Berl). 2000 Jul;150(4):430-42
references.pmid: 10958085
references.citation: Drug Alcohol Depend. 2001 Aug 1;63(3):215-28
references.pmid: 11418226
references.citation: Contemp Top Lab Anim Sci. 2000 Nov;39(6):18-23
references.pmid: 11487247
references.citation: Contemp Top Lab Anim Sci. 2001 Nov;40(6):15-7
references.pmid: 11703050
references.citation: Brain Res. 2001 Nov 30;920(1-2):97-105
references.pmid: 11716815
references.citation: Comp Med. 2001 Feb;51(1):43-8
references.pmid: 11926301
references.citation: Pain. 2002 May;97(1-2):93-103
references.pmid: 12031783
references.citation: Contemp Top Lab Anim Sci. 2002 Jul;41(4):8-14
references.pmid: 12109891
references.citation: Contemp Top Lab Anim Sci. 2002 Jul;41(4):15-22
references.pmid: 12109892
references.citation: Lab Anim. 2002 Jul;36(3):322-43
references.pmid: 12144743
references.citation: Eur J Pharmacol. 2002 Oct 4;452(2):163-73
references.pmid: 12354566
references.citation: Acta Pharmacol Sin. 2003 Jan;24(1):85-90
references.pmid: 12511234
references.citation: J Neurosci. 2003 Nov 12;23(32):10331-7
references.pmid: 14614092
references.citation: Acta Pharmacol Sin. 2003 Dec;24(12):1265-9
references.pmid: 14653955
references.citation: Pain. 2003 Dec;106(3):381-91
references.pmid: 14659521
references.citation: Chirality. 2004 Feb;16(2):112-8
references.pmid: 14712474
references.citation: Eur J Pharmacol. 2004 Oct 1;500(1-3):351-69
references.pmid: 15464045
references.citation: Clin Pharmacokinet. 2004;43(13):879-923
references.pmid: 15509185
references.citation: Br J Pharmacol. 1977 Aug;60(4):537-45
references.pmid: 409448
references.citation: Pharmacol Biochem Behav. 1987 Mar;26(3):483-9
references.pmid: 3575365
references.citation: Science. 2000 Apr 14;288(5464):306-13
references.pmid: 10764638
references.citation: Lab Anim. 1999 Apr;33(2):169-74
references.pmid: 10780821
references.citation: J Pain. 2005 Jun;6(6):372-83
references.pmid: 15943959
references.citation: Pain. 2005 Aug;116(3):386-95
references.pmid: 15982812
references.citation: Gend Med. 2005 Sep;2(3):137-45
references.pmid: 16290886
references.citation: Eur J Pain. 2006 Oct;10(7):597-601
references.pmid: 16226908
references.citation: J Am Assoc Lab Anim Sci. 2006 Nov;45(6):13-6
references.pmid: 17089985
references.citation: Pain. 2006 Dec 15;126(1-3):234-44
references.pmid: 16949748
references.citation: Chirality. 2007 Mar;19(3):190-6
references.pmid: 17192836
references.citation: Lab Anim. 2007 Apr;41(2):185-96
references.pmid: 17430618
references.citation: Pain. 2007 Nov;132 Suppl 1:S26-45
references.pmid: 17964077
references.citation: J Vet Pharmacol Ther. 2008 Oct;31(5):415-22
references.pmid: 19000260
references.citation: Comp Med. 2009 Feb;59(1):60-71
references.pmid: 19295055
references.citation: J Neurosci. 2009 Jun 3;29(22):7341-8
references.pmid: 19494155
references.citation: J Pharmacol Exp Ther. 2005 Jun;313(3):1136-49
references.pmid: 15701707