title: An overview of animal models of pain: disease models and outcome measures.
abstract: Pain is ultimately a perceptual phenomenon. It is built from information gathered by specialized pain receptors in tissue, modified by spinal and supraspinal mechanisms, and integrated into a discrete sensory experience with an emotional valence in the brain. Because of this, studying intact animals allows the multidimensional nature of pain to be examined. A number of animal models have been developed, reflecting observations that pain phenotypes are mediated by distinct mechanisms. Animal models of pain are designed to mimic distinct clinical diseases to better evaluate underlying mechanisms and potential treatments. Outcome measures are designed to measure multiple parts of the pain experience, including reflexive hyperalgesia measures, sensory and affective dimensions of pain, and impact of pain on function and quality of life. In this review, we discuss the common methods used for inducing each of the pain phenotypes related to clinical pain syndromes as well as the main behavioral tests for assessing pain in each model.
  
  
  CONCLUSIONS
  Understanding animal models and outcome measures in animals will assist in translating data from basic science to the clinic.
authors.affiliation: Department of Physical Therapy and Rehabilitation Science, College of Medicine, University of Iowa, Iowa City, Iowa; Neuroscience Graduate Program, College of Medicine, University of Iowa, Iowa City, Iowa.
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Gregory
authors.forename: Amber L
authors.initials: AL
authors.lastname: Harris
authors.forename: Caleb R
authors.initials: CR
authors.lastname: Robinson
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Dougherty
authors.forename: Perry N
authors.initials: PN
authors.lastname: Fuchs
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Sluka
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D004195:Disease Models, Animal; D006930:Hyperalgesia / Q000503:physiopathology / Q000628:therapy; D009437:Neuralgia / Q000503:physiopathology / Q000628:therapy; D010146:Pain / Q000503:physiopathology*; D059408:Pain Management; D010147:Pain Measurement
keywords: Pain; affective; animal model; behavior; cancer; escape-avoidance; incision; inflammation; joint; muscle; neuropathic; place preference; reflex
references.citation: Exp Brain Res. 2006 Mar;169(4):467-72
references.pmid: 16292641
references.citation: Pain. 2008 Nov 30;140(2):254-264
references.pmid: 18835099
references.citation: Pain. 2008 Nov 30;140(2):292-304
references.pmid: 18834667
references.citation: Mol Pain. 2008 Oct 01;4:43
references.pmid: 18828909
references.citation: Pain. 2003 Aug;104(3):567-577
references.pmid: 12927629
references.citation: Neurosci Lett. 1993 Jul 9;157(1):115-9
references.pmid: 8233021
references.citation: Pain. 1992 Sep;50(3):355-363
references.pmid: 1333581
references.citation: Pain. 2012 Nov;153(11):2192-2203
references.pmid: 22840570
references.citation: Eur J Pain. 2009 Oct;13(9):915-23
references.pmid: 19095475
references.citation: Pain. 2001 Mar;91(1-2):33-45
references.pmid: 11240076
references.citation: J Orofac Pain. 1995 Fall;9(4):347-56
references.pmid: 8995906
references.citation: Pain. 2003 Jul;104(1-2):241-7
references.pmid: 12855334
references.citation: Future Med Chem. 2012 Jun;4(10):1243-55
references.pmid: 22800369
references.citation: J Pain. 2009 Oct;10(10):1073-7
references.pmid: 19576859
references.citation: Arthritis Rheum. 2013 Feb;65(2):363-72
references.pmid: 22961435
references.citation: Pain. 2005 Nov;118(1-2):176-84
references.pmid: 16154700
references.citation: Neuroscience. 2009 Jun 16;161(1):173-83
references.pmid: 19324079
references.citation: Curr Pain Headache Rep. 2008 Oct;12(5):338-43
references.pmid: 18765138
references.citation: Best Pract Res Clin Rheumatol. 2007 Jun;21(3):427-45
references.pmid: 17602992
references.citation: Brain Res. 2008 Sep 16;1230:91-8
references.pmid: 18657527
references.citation: Proc Soc Exp Biol Med. 1965 Mar;118:763-6
references.pmid: 14268686
references.citation: Eur J Pain. 2008 Apr;12(3):361-70
references.pmid: 17768078
references.citation: J Pain. 2012 Feb;13(2):195-206
references.pmid: 22245361
references.citation: Cephalalgia. 2013 Oct;33(13):1096-105
references.pmid: 23666930
references.citation: Pain. 1989 Feb;36(2):239-247
references.pmid: 2919104
references.citation: Science. 1997 Aug 15;277(5328):968-71
references.pmid: 9252330
references.citation: Eur J Pain. 2010 Mar;14(3):236-44
references.pmid: 19560379
references.citation: Biol Sex Differ. 2011 Nov 10;2:12
references.pmid: 22074728
references.citation: Agents Actions. 1988 Dec;25(3-4):210-3
references.pmid: 3218593
references.citation: Br J Haematol. 2012 Feb;156(4):535-44
references.pmid: 22171826
references.citation: Neurosci Lett. 1994 Sep 26;179(1-2):21-4
references.pmid: 7845616
references.citation: Arthritis Rheum. 2009 Nov;60(11):3229-40
references.pmid: 19877043
references.citation: J Pain. 2007 May;8(5):422-9
references.pmid: 17293165
references.citation: J Pain. 2003 Oct;4(8):455-64
references.pmid: 14622666
references.citation: Nat Rev Rheumatol. 2010 Oct;6(10):599-606
references.pmid: 20664523
references.citation: Pain. 1990 May;41(2):167-234
references.pmid: 2195438
references.citation: Eur J Neurosci. 2003 May;17(9):1907-20
references.pmid: 12752790
references.citation: Eur J Pain. 2002;6(4):295-305
references.pmid: 12161095
references.citation: Semin Neurol. 2012 Jul;32(3):264-8
references.pmid: 23117951
references.citation: Arch Phys Med Rehabil. 2005 Sep;86(9):1736-40
references.pmid: 16181935
references.citation: Pain. 1996 Nov;68(1):97-107
references.pmid: 9252004
references.citation: Am J Physiol Gastrointest Liver Physiol. 2012 Oct;303(7):G817-24
references.pmid: 22859364
references.citation: J Pain Symptom Manage. 2005 May;29(5 Suppl):S32-46
references.pmid: 15907645
references.citation: Annu Rev Neurosci. 2009;32:1-32
references.pmid: 19400724
references.citation: Eur J Pharmacol. 1979 Jul 15;57(1):43-55
references.pmid: 477741
references.citation: Physiol Behav. 2009 Sep 7;98(3):263-7
references.pmid: 19505486
references.citation: Arthritis Rheum. 2010 Oct;62(10):2995-3005
references.pmid: 20556813
references.citation: Clin Cancer Res. 2012 Jun 1;18(11):3180-7
references.pmid: 22496202
references.citation: Curr Mol Pharmacol. 2008 Nov;1(3):255-69
references.pmid: 20021438
references.citation: Pain. 2010 Nov;151(2):394-403
references.pmid: 20739123
references.citation: Pain. 1989 Jul;38(1):99-107
references.pmid: 2780068
references.citation: J Pharmacol Exp Ther. 1970 Nov;175(2):435-42
references.pmid: 4394803
references.citation: Life Sci. 2001 Jun 15;69(4):443-54
references.pmid: 11459435
references.citation: Pain. 1996 Mar;64(3):493-502
references.pmid: 8783314
references.citation: J Biomed Sci. 2012 Aug 21;19:77
references.pmid: 22909215
references.citation: Exp Neurol. 2000 Jun;163(2):490-4
references.pmid: 10833324
references.citation: Expert Opin Drug Discov. 2008 Sep;3(9):1099-108
references.pmid: 23506182
references.citation: J Neurophysiol. 1988 May;59(5):1395-409
references.pmid: 3385466
references.citation: Pain. 1990 Dec;43(3):377-386
references.pmid: 2293146
references.citation: J Urol. 2008 Feb;179(2):759-63
references.pmid: 18082197
references.citation: Pain. 1991 May;45(2):175-185
references.pmid: 1652116
references.citation: Pain. 2003 Dec;106(3):337-345
references.pmid: 14659516
references.citation: Exp Brain Res. 2009 Jun;196(1):5-11
references.pmid: 19294370
references.citation: Pain. 2005 Jan;113(1-2):9-19
references.pmid: 15621359
references.citation: BMC Musculoskelet Disord. 2008 Apr 17;9:52
references.pmid: 18419803
references.citation: Eur J Pain. 2007 May;11(4):398-405
references.pmid: 16872852
references.citation: Mol Pain. 2009 Aug 12;5:48
references.pmid: 19674450
references.citation: Pain Med. 2007 Sep;8 Suppl 2:S50-62
references.pmid: 17714116
references.citation: Life Sci. 1989;45(23):2217-24
references.pmid: 2601574
references.citation: Pain. 2000 Feb;84(2-3):141-9
references.pmid: 10666518
references.citation: Pain. 2010 Jun;149(3):573-581
references.pmid: 20418016
references.citation: J Pain. 2011 Aug;12(8):868-74
references.pmid: 21515090
references.citation: J Neurosci Methods. 2000 Apr 1;97(1):19-29
references.pmid: 10771071
references.citation: Anesthesiology. 1996 May;84(5):1177-88
references.pmid: 8624012
references.citation: Pain. 2007 Dec 15;133(1-3):47-63
references.pmid: 17433546
references.citation: Brain Res. 1988 May 31;450(1-2):153-69
references.pmid: 3401708
references.citation: Mol Pain. 2011 May 20;7:40
references.pmid: 21599974
references.citation: Novartis Found Symp. 2004;261:194-214; discussion 214-9, 256-61
references.pmid: 15469052
references.citation: Neuroscience. 2008 Mar 18;152(2):521-5
references.pmid: 18280048
references.citation: Pain. 1993 Dec;55(3):367-377
references.pmid: 7510059
references.citation: Eur J Pain. 1999 Jun;3(2):93-102
references.pmid: 10700339
references.citation: J Neurophysiol. 1985 Nov;54(5):1109-22
references.pmid: 4078610
references.citation: J Neurosci. 1988 Aug;8(8):2780-7
references.pmid: 2900881
references.citation: Nat Rev Neurosci. 2009 Apr;10(4):283-94
references.pmid: 19259101
references.citation: Pain. 1999 Feb;79(2-3):135-41
references.pmid: 10068159
references.citation: Muscle Nerve. 1997 Feb;20(2):198-204
references.pmid: 9040659
references.citation: Arthritis Rheum. 2013 May;65(5):1194-202
references.pmid: 23335302
references.citation: Pain. 1986 Apr;25(1):83-93
references.pmid: 3714289
references.citation: Nature. 1983 Dec 15-21;306(5944):686-8
references.pmid: 6656869
references.citation: Pain. 2000 Aug;87(2):149-158
references.pmid: 10924808
references.citation: Pain. 2011 Sep;152(9):1976-1987
references.pmid: 21550725
references.citation: Pain. 2011 Oct;152(10):2248-2258
references.pmid: 21696889
references.citation: Acta Neuropathol. 1978 Feb 20;41(2):131-7
references.pmid: 205081
references.citation: Minerva Anestesiol. 2006 Mar;72(3):151-69
references.pmid: 16493391
references.citation: Pharmacol Biochem Behav. 2012 Oct;102(4):520-5
references.pmid: 22789876
references.citation: Cell. 2009 Oct 16;139(2):267-84
references.pmid: 19837031
references.citation: Neurosci Lett. 2000 Aug 18;290(1):79-83
references.pmid: 10925179
references.citation: Pain. 2010 Feb;148(2):188-197
references.pmid: 19632780
references.citation: Muscle Nerve. 2001 Jan;24(1):37-46
references.pmid: 11150964
references.citation: Pain. 2005 May;115(1-2):95-106
references.pmid: 15836973
references.citation: Brain Res. 1980 Nov 17;201(2):475-9
references.pmid: 6893423
references.citation: Pain. 2012 Aug;153(8):1657-1663
references.pmid: 22664319
references.citation: Neuron. 1998 Sep;21(3):531-43
references.pmid: 9768840
references.citation: Eur J Neurosci. 2010 Sep;32(5):819-25
references.pmid: 20726881
references.citation: Arch Int Pharmacodyn Ther. 1957 Sep 1;111(4):409-19
references.pmid: 13471093
references.citation: Neurosci Lett. 1993 Apr 16;153(1):9-12
references.pmid: 8510831
references.citation: Cancer Chemother Pharmacol. 2013 Mar;71(3):619-26
references.pmid: 23228992
references.citation: Pain. 2008 Jun;136(3):331-339
references.pmid: 17764841
references.citation: Foot Ankle Clin. 2004 Jun;9(2):271-85
references.pmid: 15165582
references.citation: Anesth Analg. 1998 Nov;87(5):1121-4
references.pmid: 9806693
references.citation: Rheumatology (Oxford). 2012 Nov;51(11):1931-41
references.pmid: 22427408
references.citation: Neurosci Lett. 2012 Mar 5;511(1):18-22
references.pmid: 22281447
references.citation: J Neurosci. 2002 Jul 1;22(13):5687-93
references.pmid: 12097520
references.citation: Pain Med. 2000 Dec;1(4):303-9
references.pmid: 15101876
references.citation: J Neurosci Methods. 2007 Jun 15;163(1):67-75
references.pmid: 17383008
references.citation: Pain. 1988 Jan;32(1):77-88
references.pmid: 3340425
references.citation: BMC Musculoskelet Disord. 2013 Jan 08;14:14
references.pmid: 23297850
references.citation: Pain. 1977 Dec;4(2):161-174
references.pmid: 564014
references.citation: Pain. 2003 Aug;104(3):579-588
references.pmid: 12927630
references.citation: Neuroscience. 2011 Jun 30;185:166-73
references.pmid: 21513773
references.citation: Pain. 1981 Feb;10(1):67-73
references.pmid: 7194999
references.citation: Open Orthop J. 2012;6:558-63
references.pmid: 23248728
references.citation: Neuropharmacology. 2010 Jan;58(1):156-65
references.pmid: 19607849
references.citation: Science. 2005 Mar 4;307(5714):1468-72
references.pmid: 15746429
references.citation: Proc West Pharmacol Soc. 2002;45:211-8
references.pmid: 12434582
references.citation: Pain. 2002 Mar;96(1-2):141-51
references.pmid: 11932070
references.citation: Pain. 1998 Oct;78(1):59-69
references.pmid: 9822212
references.citation: J Neurosci Methods. 2007 Jun 15;163(1):9-16
references.pmid: 17382401
references.citation: J Neurol Neurosurg Psychiatry. 1979 May;42(5):422-35
references.pmid: 448382
references.citation: J Physiol. 2000 Nov 15;529 Pt 1:243-62
references.pmid: 11080266
references.citation: Neuroscience. 1996 Jan;70(2):391-407
references.pmid: 8848148
references.citation: J Pain. 2011 Sep;12(9):1017-24
references.pmid: 21703938
references.citation: Exp Diabetes Res. 2009;2009:431980
references.pmid: 20148083
references.citation: J Physiol. 2001 Dec 1;537(Pt 2):333-45
references.pmid: 11731568
references.citation: Pain. 2012 Apr;153(4):876-884
references.pmid: 22341563
references.citation: Nat Neurosci. 2009 Nov;12(11):1364-6
references.pmid: 19783992
references.citation: J Pain. 2006 Jan;7(1):32-9
references.pmid: 16414552
references.citation: Eur J Pain. 2003;7(2):145-53
references.pmid: 12600796
references.citation: Mol Pain. 2011 Oct 26;7:84
references.pmid: 22029713
references.citation: Neurology. 2008 Apr 29;70(18):1630-5
references.pmid: 18003941
references.citation: Brain Res. 1975 Aug 29;94(2):279-96
references.pmid: 125141
references.citation: Eur J Pharmacol. 2004 Mar 8;487(1-3):93-103
references.pmid: 15033380
references.citation: Curr Drug Targets. 2008 Jan;9(1):3-13
references.pmid: 18220709
references.citation: Brain. 2004 Jun;127(Pt 6):1403-14
references.pmid: 15069022
references.citation: Pain. 2004 Jan;107(1-2):147-58
references.pmid: 14715401
references.citation: Pain. 1992 Sep;50(3):331-344
references.pmid: 1454389
references.citation: Lancet. 1999 Jun 19;353(9170):2145-8
references.pmid: 10382712
references.citation: Am J Physiol Gastrointest Liver Physiol. 2007 Oct;293(4):G749-57
references.pmid: 17656446
references.citation: Pain. 1988 Nov;35(2):179-186
references.pmid: 2853321
references.citation: Neuroscience. 2011 Apr 28;180:334-43
references.pmid: 21315808
references.citation: Eur J Pharmacol. 2002 Apr 26;441(3):185-91
references.pmid: 12063091
references.citation: J Neurosci. 1994 May;14(5 Pt 1):2708-23
references.pmid: 8182437
references.citation: Pharmacol Rev. 2012 Oct;64(4):939-71
references.pmid: 23023032
references.citation: Pharmacol Biochem Behav. 2011 Jan;97(3):603-10
references.pmid: 21111752
references.citation: Exp Neurol. 2004 Jul;188(1):139-48
references.pmid: 15191810
references.citation: Pain. 2011 Mar;152(3 Suppl):S2-S15
references.pmid: 20961685
references.citation: Curr Protoc Pharmacol. 2004 Sep 1;Chapter 5:Unit 5.35
references.pmid: 22294122
references.citation: J Rheumatol. 2000 Feb;27(2):441-7
references.pmid: 10685812
references.citation: J Urol. 2013 Jan;189(1):343-51
references.pmid: 23174261
references.citation: Exp Neurol. 2006 Jan;197(1):22-30
references.pmid: 15996657
references.citation: Br J Pharmacol. 1997 Nov;122(6):1165-73
references.pmid: 9401782
references.citation: J Pain. 2005 Jan;6(1):41-7
references.pmid: 15629417
references.citation: Phys Ther. 2013 Oct;93(10):1397-402
references.pmid: 23641031
references.citation: Nat Rev Neurosci. 2009 Jan;10(1):23-36
references.pmid: 19096368
references.citation: Brain Res. 2013 Jan 23;1491:213-24
references.pmid: 23146715
references.citation: Pain. 2001 Dec;94(3):231-244
references.pmid: 11731060
references.citation: Mol Pain. 2010 Mar 26;6:18
references.pmid: 20346101
references.citation: Ann Rehabil Med. 2012 Apr;36(2):291-6
references.pmid: 22639758
references.citation: Pain. 1998 Mar;75(1):141-155
references.pmid: 9539683
references.citation: Ann Neurol. 2013 Aug;74(2):257-65
references.pmid: 23686557
references.citation: J Neurophysiol. 1987 Jun;57(6):1867-92
references.pmid: 3598634
references.citation: Trends Pharmacol Sci. 2000 Jul;21(7):244-6
references.pmid: 10871891
references.citation: J Pain. 2007 Sep;8(9):692-9
references.pmid: 17627895
references.citation: Annu Rev Pharmacol Toxicol. 1980;20:441-62
references.pmid: 7387124
references.citation: J Biomed Biotechnol. 2011;2011:939023
references.pmid: 21436995
references.citation: Anesthesiology. 2007 Feb;106(2):312-22
references.pmid: 17264726
references.citation: Mol Interv. 2010 Jun;10(3):164-78
references.pmid: 20539035
references.citation: Behav Brain Res. 2011 Mar 1;217(2):477-80
references.pmid: 20974188
references.citation: J Neurophysiol. 1987 Oct;58(4):850-65
references.pmid: 2824712
references.citation: Exp Brain Res. 1971;13(2):140-58
references.pmid: 4998892
references.citation: Pain. 1996 Mar;64(3):415-423
references.pmid: 8783304
references.citation: Eur J Pharmacol. 2011 Dec 15;672(1-3):83-7
references.pmid: 21996314
references.citation: Pain. 2011 May;152(5):990-1000
references.pmid: 21256675
references.citation: Pain. 1988 Apr;33(1):87-107
references.pmid: 2837713
references.citation: Phys Ther. 2012 Jul;92(7):898-910
references.pmid: 22466027
references.citation: Physiol Behav. 1996 Dec;60(6):1425-34
references.pmid: 8946486
references.citation: Pain. 1994 Sep;58(3):355-366
references.pmid: 7838585
references.citation: Exp Clin Psychopharmacol. 2008 Oct;16(5):357-66
references.pmid: 18837632
references.citation: Neuroscience. 2013 Sep 17;248:54-60
references.pmid: 23747349
references.citation: J Orthop Sports Phys Ther. 2011 Mar;41(3):165-73
references.pmid: 21169718
references.citation: Pain. 2010 Nov;151(2):540-549
references.pmid: 20850221
references.citation: Neurosci Lett. 1992 Jun 22;140(2):181-4
references.pmid: 1501774
references.citation: Nat Med. 2000 May;6(5):521-8
references.pmid: 10802707
references.citation: Neuroscience. 2007 Nov 9;149(3):650-9
references.pmid: 17928159
references.citation: Anesthesiology. 1999 Mar;90(3):863-72
references.pmid: 10078689
references.citation: Eur J Pain. 2010 Apr;14(4):343-50
references.pmid: 19695912
references.citation: Pain. 2005 Aug;116(3):386-395
references.pmid: 15982812
references.citation: J Pain. 2006 Sep;7(9):659-70
references.pmid: 16942952
references.citation: Proc Natl Acad Sci U S A. 2001 Jul 3;98(14):8077-82
references.pmid: 11416168
references.citation: J Neurosci. 2012 Oct 31;32(44):15439-49
references.pmid: 23115181
references.citation: J Physiol. 2005 Apr 1;564(Pt 1):259-68
references.pmid: 15677691
references.citation: J Appl Physiol (1985). 2013 Mar 15;114(6):725-33
references.pmid: 23271699
references.citation: Pain. 2001 Dec;94(3):293-304
references.pmid: 11731066
references.citation: Eur J Pain. 2013 Apr;17(4):514-26
references.pmid: 23169679
references.citation: Pain. 1996 Aug;66(2-3):297-306
references.pmid: 8880853
references.citation: J Gen Intern Med. 2010 Oct;25(10):1064-70
references.pmid: 20532650
references.citation: J Pain. 2012 Jun;13(6):598-607
references.pmid: 22609247