title: Central pain mechanisms in chronic pain states--maybe it is all in their head.
abstract: Mechanisms underlying chronic pain differ from those underlying acute pain. In chronic pain states, central nervous system (CNS) factors appear to play particularly prominent roles. In the absence of anatomical causes of persistent pain, medical sub-specialities have historically applied wide-ranging labels (e.g., fibromyalgia (FM), irritable bowel syndrome, interstitial cystitis and somatisation) for what now is emerging as a single common set of CNS processes. The hallmark of these 'centrally driven' pain conditions is a diffuse hyperalgesic state identifiable using experimental sensory testing, and corroborated by functional neuroimaging. The characteristic symptoms of these central pain conditions include multifocal pain, fatigue, insomnia, memory difficulties and a higher rate of co-morbid mood disorders. In contrast to acute and peripheral pain states that are responsive to non-steroidal anti-inflammatory drugs (NSAIDs) and opioids, central pain conditions respond best to CNS neuromodulating agents, such as serotonin-norepinephrine reuptake inhibitors (SNRIs) and anticonvulsants.
authors.affiliation: University of Michigan, Ann Arbor, MI, United States. kphill@med.umich.edu
authors.forename: Kristine
authors.initials: K
authors.lastname: Phillips
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Clauw
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000627:therapeutic use; D000701:Analgesics, Opioid / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D000927:Anticonvulsants / Q000627:therapeutic use; D002493:Central Nervous System Diseases / Q000175:diagnosis* / Q000188:drug therapy / Q000503:physiopathology; D059350:Chronic Pain / Q000175:diagnosis* / Q000188:drug therapy / Q000503:physiopathology; D005356:Fibromyalgia / Q000150:complications / Q000175:diagnosis* / Q000188:drug therapy / Q000503:physiopathology; D059907:Functional Neuroimaging; D006801:Humans; D006930:Hyperalgesia / Q000473:pathology / Q000503:physiopathology; D010003:Osteoarthritis / Q000150:complications / Q000175:diagnosis / Q000503:physiopathology; D010146:Pain / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology; D010523:Peripheral Nervous System Diseases / Q000175:diagnosis* / Q000188:drug therapy / Q000503:physiopathology; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use; D013577:Syndrome
chemical_list: D018759:Adrenergic Uptake Inhibitors; D000701:Analgesics, Opioid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000927:Anticonvulsants; D017367:Selective Serotonin Reuptake Inhibitors
references.citation: Arthritis Rheum. 2006 May;54(5):1682-6
references.pmid: 16646040
references.citation: Best Pract Res Clin Rheumatol. 2003 Aug;17(4):593-609
references.pmid: 12849714
references.citation: Hong Kong Med J. 2009 Jun;15(3):168-72
references.pmid: 19494370
references.citation: Best Pract Res Clin Rheumatol. 2007 Feb;21(1):153-66
references.pmid: 17350550
references.citation: Pain. 2000 Oct;88(1):69-78
references.pmid: 11098101
references.citation: J Rheumatol. 1997 Mar;24(3):555-9
references.pmid: 9058665
references.citation: JAMA. 1998 Sep 16;280(11):981-8
references.pmid: 9749480
references.citation: Curr Opin Anaesthesiol. 2005 Oct;18(5):555-62
references.pmid: 16534292
references.citation: Pain. 2006 Aug;123(3):226-230
references.pmid: 16777329
references.citation: Am J Psychiatry. 1985 Apr;142(4):441-6
references.pmid: 3856400
references.citation: Pain Med. 2007 Nov-Dec;8(8):633-8
references.pmid: 18028041
references.citation: Adv Nurse Pract. 2001 Nov;9(11):28-36
references.pmid: 12420497
references.citation: Arthritis Rheum. 2009 Feb;60(2):321-4
references.pmid: 19180503
references.citation: Curr Opin Support Palliat Care. 2007 Aug;1(2):109-16
references.pmid: 18685351
references.citation: J Rheumatol. 1993 Nov;20(11):1925-31
references.pmid: 7848390
references.citation: J Rheumatol Suppl. 1989 Nov;19:185-91
references.pmid: 2691678
references.citation: Semin Arthritis Rheum. 2008 Jun;37(6):339-52
references.pmid: 18191990
references.citation: Arthritis Rheum. 2009 Feb;60(2):628-9
references.pmid: 19180497
references.citation: J Rheumatol. 1997 May;24(5):941-4
references.pmid: 9150086
references.citation: J Rheumatol. 2006 Nov;33(11):2291-9
references.pmid: 16960921
references.citation: Annu Rev Neurosci. 2003;26:1-30
references.pmid: 12651967
references.citation: J Psychosom Res. 2009 Jan;66(1):51-7
references.pmid: 19073294
references.citation: J Psychiatr Res. 1997 Jan-Feb;31(1):125-31
references.pmid: 9201654
references.citation: Pain. 1997 Mar;70(1):41-51
references.pmid: 9106808
references.citation: Gen Hosp Psychiatry. 2009 May-Jun;31(3):206-19
references.pmid: 19410099
references.citation: Z Rheumatol. 1998;57 Suppl 2:63-6
references.pmid: 10025086
references.citation: Drugs Aging. 1996 Jun;8(6):459-76
references.pmid: 8736630
references.citation: Arthritis Rheum. 2003 Oct;48(10):2916-22
references.pmid: 14558098
references.citation: Ann Rheum Dis. 1997 Apr;56(4):268-71
references.pmid: 9166001
references.citation: Arthritis Rheum. 2004 Mar;50(3):944-52
references.pmid: 15022338
references.citation: Eur J Pain. 2008 Apr;12(3):329-38
references.pmid: 17723312
references.citation: J Rheumatol. 2001 Nov;28(11):2568-9
references.pmid: 11708444
references.citation: J Pain. 2009 Aug;10(8):777-91
references.pmid: 19638325
references.citation: Life Sci. 2004 Apr 9;74(21):2605-10
references.pmid: 15041442
references.citation: Arthritis Rheum. 1996 Mar;39(3):436-45
references.pmid: 8607892
references.citation: Ann Rheum Dis. 1975 Apr;34(2):195-6
references.pmid: 1137445
references.citation: Pain. 2002 Nov;100(1-2):131-9
references.pmid: 12435466
references.citation: Arch Intern Med. 2006 Aug 14-28;166(15):1649-54
references.pmid: 16908799
references.citation: Arthritis Rheum. 2002 May;46(5):1333-43
references.pmid: 12115241
references.citation: Best Pract Res Clin Rheumatol. 2007 Jun;21(3):535-47
references.pmid: 17602998
references.citation: Pain. 2001 Aug;93(2):107-114
references.pmid: 11427321
references.citation: Support Care Cancer. 2001 Jan;9(1):48-54
references.pmid: 11147143
references.citation: West J Med. 1981 May;134(5):405-13
references.pmid: 6167073
references.citation: Ann Intern Med. 2004 Mar 16;140(6):441-51
references.pmid: 15023710
references.citation: Womens Health Issues. 1996 Nov-Dec;6(6):320-31
references.pmid: 8990964
references.citation: J Neurosci. 2007 Sep 12;27(37):10000-6
references.pmid: 17855614
references.citation: Eur J Pain. 2000;4(3):229-38
references.pmid: 10985866
references.citation: Arthritis Rheum. 2004 Feb;50(2):613-23
references.pmid: 14872506
references.citation: J Rheumatol. 1993 Feb;20(2):344-51
references.pmid: 8474074
references.citation: Arthritis Rheum. 1993 May;36(5):642-6
references.pmid: 8489541
references.citation: J Urol. 2009 Nov;182(5):2123-31
references.pmid: 19758633
references.citation: BMC Musculoskelet Disord. 2004 Dec 09;5:48
references.pmid: 15588296
references.citation: Pain. 2004 Jan;107(1-2):5-6
references.pmid: 14715382
references.citation: J Rheumatol Suppl. 1989 Nov;19:144-9
references.pmid: 2691674
references.citation: Pain. 2007 Mar;128(1-2):1-2
references.pmid: 17254713
references.citation: Curr Pain Headache Rep. 2007 Oct;11(5):343-51
references.pmid: 17894924
references.citation: Semin Arthritis Rheum. 2010 Jun;39(6):477-90
references.pmid: 19136144
references.citation: Pain. 2009 Dec;146(3):253-260
references.pmid: 19625125
references.citation: Hum Mol Genet. 2005 Jan 1;14(1):135-43
references.pmid: 15537663
references.citation: Arthritis Rheum. 2008 Jun 15;59(6):849-56
references.pmid: 18512720
references.citation: J Clin Rheumatol. 2007 Apr;13(2):102-9
references.pmid: 17414543
references.citation: Psychol Med. 2009 Mar;39(3):497-505
references.pmid: 18578896
references.citation: Compr Ther. 1984 Aug;10(8):21-8
references.pmid: 6590171
references.citation: Neuroimmunomodulation. 1997 May-Jun;4(3):134-53
references.pmid: 9500148
references.citation: Br J Rheumatol. 1997 Jul;36(7):726-8
references.pmid: 9255104
references.citation: Mol Pain. 2009 Sep 23;5:56
references.pmid: 19775452
references.citation: Rheum Dis Clin North Am. 2009 May;35(2):339-57
references.pmid: 19647147
references.citation: Med Hypotheses. 2004;63(4):653-8
references.pmid: 15325010
references.citation: Arthritis Res Ther. 2006;8(5):218
references.pmid: 16887010
references.citation: J Rheumatol. 2000 Feb;27(2):441-7
references.pmid: 10685812
references.citation: Arthritis Rheum. 1995 Jan;38(1):19-28
references.pmid: 7818567
references.citation: Pain. 2006 Dec 5;125(3):216-224
references.pmid: 16837133
references.citation: CNS Spectr. 2008 Mar;13(3 Suppl 5):12-7
references.pmid: 18323768
references.citation: Science. 2003 Feb 21;299(5610):1240-3
references.pmid: 12595695
references.citation: J Rheumatol. 1984 Oct;11(5):678-80
references.pmid: 6595407
references.citation: Electroencephalogr Clin Neurophysiol. 1980 Oct;50(1-2):71-80
references.pmid: 6159193
references.citation: Pain. 1995 Dec;63(3):341-351
references.pmid: 8719535
references.citation: Arthritis Rheum. 2008 Mar;58(3):903-7
references.pmid: 18311814
references.citation: Eur J Pain. 2007 Feb;11(2):202-7
references.pmid: 16546424
references.citation: J Rheumatol. 1994 Mar;21(3):579-80
references.pmid: 8006910
references.citation: J Rheumatol. 2008 Jun;35(6):1102-7
references.pmid: 18484690
references.citation: Nurs Times. 2003 Nov 11-17;99(45):42-3
references.pmid: 14649184
references.citation: J Pain Symptom Manage. 1999 Jun;17(6):391-401
references.pmid: 10388244
references.citation: Pain. 1994 Aug;58(2):185-193
references.pmid: 7816486
references.citation: J Rheumatol Suppl. 1989 Nov;19:28-9
references.pmid: 2607512
references.citation: Gastroenterology. 2006 Apr;130(5):1377-90
references.pmid: 16678553
references.citation: Am J Med Sci. 1998 Jun;315(6):346-50
references.pmid: 9638890
references.citation: J Rheumatol. 1999 Jul;26(7):1564-9
references.pmid: 10405946
references.citation: J Urol. 2005 Nov;174(5):1837-40
references.pmid: 16217303
references.citation: Gut. 2005 May;54(5):569-73
references.pmid: 15831894
references.citation: BMJ. 2009 Aug 21;339:b2844
references.pmid: 19700505
references.citation: Pain. 2003 Dec;106(3):393-400
references.pmid: 14659522
references.citation: Gerontologist. 2005 Oct;45 Spec No 1(1):68-73
references.pmid: 16230752
references.citation: Arthritis Rheum. 2009 Sep 15;61(9):1226-34
references.pmid: 19714588
references.citation: Arch Gen Psychiatry. 1975 Feb;32(2):193-7
references.pmid: 1115567
references.citation: Arch Neurol. 1993 Oct;50(10):1061-4
references.pmid: 8215965
references.citation: Arthritis Rheum. 2005 May;52(5):1577-84
references.pmid: 15880832
references.citation: Pain. 2003 Oct;105(3):403-413
references.pmid: 14527701
references.citation: J Psychosom Res. 2008 Jun;64(6):599-604
references.pmid: 18501260
references.citation: J Rheumatol Suppl. 1989 Nov;19:15-22
references.pmid: 2691675