title: Alterations in endogenous opioid functional measures in chronic back pain.
abstract: The absence of consistent end organ abnormalities in many chronic pain syndromes has led to a search for maladaptive CNS mechanisms that may explain their clinical presentations and course. Here, we addressed the role of brain regional μ-opioid receptor-mediated neurotransmission, one of the best recognized mechanisms of pain regulation, in chronic back pain in human subjects. We compared μ-opioid receptor availability in vivo at baseline, during pain expectation, and with moderate levels of sustained pain in 16 patients with chronic nonspecific back pain (CNBP) and in 16 age- and gender-matched healthy control subjects, using the μ-opioid receptor-selective radioligand [(11)C]carfentanil and positron emission tomography. We found that CNBP patients showed baseline increases in thalamic μ-opioid receptor availability, contrary to a previously studied sample of patients diagnosed with fibromyalgia. During both pain expectation and sustained pain challenges, CNBP patients showed regional reductions in the capacity to activate this neurotransmitter system compared with their control sample, further associated with clinical pain and affective state ratings. Our results demonstrate heterogeneity in endogenous opioid system functional measures across pain conditions, and alterations in both receptor availability and endogenous opioid function in CNBP that are relevant to the clinical presentation of these patients and the effects of opioid analgesics on μ-opioid receptors.
authors.affiliation: Molecular and Behavioral Neuroscience Institute, and Departments of Psychiatry, Anesthesiology, Obstetrics and Gynecology, and Radiology, University of Michigan, Ann Arbor, Michigan 48109, Neuroscience Graduate Program, University of Michigan, Ann Arbor, Michigan 48104, Department of Health Management and Policy, School of Public Health, University of Michigan, Ann Arbor, Michigan 48109, and School of Dentistry, University of Maryland, Baltimore, Maryland 21201.
authors.forename: Ilkka K
authors.initials: IK
authors.lastname: Martikainen
authors.forename: Marta
authors.initials: M
authors.lastname: Peciña
authors.forename: Tiffany M
authors.initials: TM
authors.lastname: Love
authors.forename: Emily B
authors.initials: EB
authors.lastname: Nuechterlein
authors.forename: Chelsea M
authors.initials: CM
authors.lastname: Cummiford
authors.forename: Carmen R
authors.initials: CR
authors.lastname: Green
authors.forename: Richard E
authors.initials: RE
authors.lastname: Harris
authors.forename: Christian S
authors.initials: CS
authors.lastname: Stohler
authors.forename: Jon-Kar
authors.initials: JK
authors.lastname: Zubieta
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000378:metabolism*; D000704:Analysis of Variance; D001416:Back Pain / Q000000981:diagnostic imaging / Q000473:pathology*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D001931:Brain Mapping; D002250:Carbon Radioisotopes; D016022:Case-Control Studies; D002908:Chronic Disease; D005260:Female; D005283:Fentanyl / Q000031:analogs & derivatives; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D049268:Positron-Emission Tomography; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D000701:Analgesics, Opioid; D002250:Carbon Radioisotopes; C017114:carfentanil; D005283:Fentanyl
references.citation: Nat Neurosci. 2012 Jul 01;15(8):1117-9
references.pmid: 22751038
references.citation: J Comp Neurol. 1981 May 1;198(1):121-36
references.pmid: 6164704
references.citation: J Cereb Blood Flow Metab. 1992 Nov;12(6):900-18
references.pmid: 1400644
references.citation: Clin J Pain. 2004 Sep-Oct;20(5):283-92
references.pmid: 15322434
references.citation: Pain. 2000 Dec 15;89(1):7-18
references.pmid: 11113288
references.citation: Neuroimage. 2005 Jul 1;26(3):839-51
references.pmid: 15955494
references.citation: Nucl Med Biol. 2001 Aug;28(6):733-4
references.pmid: 11518656
references.citation: Lancet. 2012 Feb 4;379(9814):482-91
references.pmid: 21982256
references.citation: Pain. 2002 Oct;99(3):589-598
references.pmid: 12406535
references.citation: Nat Clin Pract Rheumatol. 2006 Jul;2(7):364-72
references.pmid: 16932722
references.citation: J Neurosci. 2009 Nov 4;29(44):13746-50
references.pmid: 19889986
references.citation: Br J Rheumatol. 1994 Oct;33(10):909-16
references.pmid: 7921749
references.citation: Eur J Pain. 2004 Oct;8(5):479-85
references.pmid: 15324779
references.citation: J Neurosurg. 1991 Mar;74(3):415-21
references.pmid: 1993906
references.citation: Eur J Pain. 2007 May;11(4):415-20
references.pmid: 16815054
references.citation: Proc Natl Acad Sci U S A. 1997 Feb 18;94(4):1544-9
references.pmid: 9037090
references.citation: Pain. 2007 Jan;127(1-2):183-94
references.pmid: 17137714
references.citation: Pain. 2006 Oct;124(3):287-294
references.pmid: 16725261
references.citation: Neuroimage. 2009 Sep;47(3):1077-85
references.pmid: 19501658
references.citation: J Neurosci. 2011 May 18;31(20):7540-50
references.pmid: 21593339
references.citation: Int J Appl Radiat Isot. 1985 Apr;36(4):303-6
references.pmid: 2991142
references.citation: IEEE Trans Biomed Eng. 1993 Apr;40(4):344-52
references.pmid: 8375871
references.citation: Brain Res. 1998 Jan 1;779(1-2):104-18
references.pmid: 9473612
references.citation: Neuron. 2005 Oct 20;48(2):175-87
references.pmid: 16242399
references.citation: J Cereb Blood Flow Metab. 1999 Jul;19(7):803-8
references.pmid: 10413036
references.citation: J Neurosci. 2002 Jun 15;22(12):5100-7
references.pmid: 12077205
references.citation: Pain. 2004 Apr;108(3):213-220
references.pmid: 15030940
references.citation: Pain. 2007 Oct;131(3):311-319
references.pmid: 17459585
references.citation: Neurology. 1994 May;44(5):857-61
references.pmid: 7514771
references.citation: Arthritis Rheum. 1990 Feb;33(2):160-72
references.pmid: 2306288
references.citation: Brain Res. 1988 Feb 16;441(1-2):173-84
references.pmid: 2833999
references.citation: J Neurosci. 2007 Sep 12;27(37):10000-6
references.pmid: 17855614
references.citation: J Cereb Blood Flow Metab. 1996 Sep;16(5):834-40
references.pmid: 8784228
references.citation: J Cereb Blood Flow Metab. 1991 Jul;11(4):690-9
references.pmid: 2050758
references.citation: Arthritis Rheum. 2004 Feb;50(2):613-23
references.pmid: 14872506
references.citation: Pain. 2002 Mar;96(1-2):153-62
references.pmid: 11932071
references.citation: Pain. 2006 Nov;125(1-2):89-97
references.pmid: 16750298
references.citation: J Neurosci. 2004 Nov 17;24(46):10410-5
references.pmid: 15548656
references.citation: J Neurosci. 2011 Sep 28;31(39):13981-90
references.pmid: 21957259
references.citation: Lancet. 1999 Aug 14;354(9178):581-5
references.pmid: 10470716
references.citation: Neuroscientist. 2004 Jun;10(3):221-34
references.pmid: 15155061
references.citation: J Nucl Med. 1993 Feb;34(2):322-9
references.pmid: 8429356
references.citation: Pain. 2002 Jan;95(1-2):31-40
references.pmid: 11790465
references.citation: Eur Spine J. 2013 Sep;22(9):1958-64
references.pmid: 23392554
references.citation: Pain. 2005 Feb;113(3):331-339
references.pmid: 15661441
references.citation: Science. 2000 Jun 9;288(5472):1765-9
references.pmid: 10846153
references.citation: Lancet. 1992 Jun 6;339(8806):1367-71
references.pmid: 1350803
references.citation: Science. 2001 Jul 13;293(5528):311-5
references.pmid: 11452128
references.citation: J Neurosci. 1998 Mar 1;18(5):1671-8
references.pmid: 9464992
references.citation: J Neurosci. 2011 Apr 20;31(16):5956-64
references.pmid: 21508220
references.citation: J Neurosci. 2013 Apr 24;33(17):7574-82
references.pmid: 23616562
references.citation: Anesthesiology. 1982 Jul;57(1):1-4
references.pmid: 7091714
references.citation: Pain. 1999 Feb;79(2-3):165-73
references.pmid: 10068162
references.citation: Eur Spine J. 2011 Jan;20(1):40-50
references.pmid: 20680369
references.citation: J Neurosci. 1987 Aug;7(8):2445-64
references.pmid: 3039080
references.citation: Pain. 2011 Apr;152(4):904-911
references.pmid: 21296501
references.citation: Pain. 2010 Jan;148(1):167-171
references.pmid: 19833435
references.citation: Psychopharmacology (Berl). 1990;102(1):112-6
references.pmid: 2144051
references.citation: Neurosci Lett. 1997 Mar 7;224(1):5-8
references.pmid: 9132689
references.citation: Pain. 1995 Oct;63(1):55-64
references.pmid: 8577491
references.citation: J Neurophysiol. 1990 Nov;64(5):1537-54
references.pmid: 2283540
references.citation: Anesthesiology. 1971 Jan;34(1):50-9
references.pmid: 4924784
references.citation: Eur J Pain. 2009 Nov;13(10):1030-5
references.pmid: 19201230