title: Temporal filtering of nociceptive information by dynamic activation of endogenous pain modulatory systems.
abstract: Endogenous pain control mechanisms have long been known to produce analgesia during "flight or fight" situations and to contribute to cognitively driven pain modulation, such as placebo analgesia. Afferent nociceptive information can also directly activate supraspinal descending modulatory systems, suggesting that these mechanisms may participate in feedback loops that dynamically alter the processing of nociceptive information. The functional significance of these feedback loops, however, remains unclear. The phenomenon of offset analgesia -- disproportionately large decreases in pain ratings evoked by small decreases in stimulus intensity -- suggests that dynamic activation of endogenous pain inhibition may contribute to the temporal filtering of nociceptive information. The neural mechanisms that mediate this phenomenon remain currently unknown. Using functional magnetic resonance imaging, we show that several regions of the midbrain and brainstem are differentially activated during offset analgesia. These activations are consistent with the location of areas such as the periaqueductal gray (PAG), rostral ventral medulla, and locus ceruleus that have substantial roles in descending inhibition of pain. This transient analgesia contributes to the temporal filtering of nociceptive information by producing a perceptual amplification of the magnitude and duration of decreases in noxious stimulus intensity. Together with the involvement of PAG and associated brainstem mechanisms in cognitively generated analgesia, the present observations suggest that the fundamental role of endogenous pain modulatory mechanisms is to dynamically shape the processing of nociceptive signals to best fit with the ever-changing demands of the environment.
authors.affiliation: Department of Neurobiology and Anatomy and Division of Radiological Sciences, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1010, USA.
authors.forename: Marc D
authors.initials: MD
authors.lastname: Yelle
authors.forename: Yoshitetsu
authors.initials: Y
authors.lastname: Oshiro
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kraft
authors.forename: Robert C
authors.initials: RC
authors.lastname: Coghill
mesh_terms: D000328:Adult; D000698:Analgesia / Q000379:methods*; D001921:Brain / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D010146:Pain / Q000503:physiopathology* / Q000517:prevention & control; D010147:Pain Measurement / Q000379:methods*; D013997:Time Factors; D055815:Young Adult
references.citation: J Neurophysiol. 1999 Oct;82(4):1934-43
references.pmid: 10515983
references.citation: Brain Res Brain Res Rev. 2003 Apr;42(1):85-95
references.pmid: 12668291
references.citation: Neuroscience. 1982;7(11):2769-76
references.pmid: 7155351
references.citation: Pain. 2008 Aug 15;138(1):22-28
references.pmid: 18079062
references.citation: J Neurophysiol. 1983 Dec;50(6):1446-59
references.pmid: 6663337
references.citation: J Comp Neurol. 1978 Mar 15;178(2):329-46
references.pmid: 415074
references.citation: Pain. 2005 Mar;114(1-2):295-302
references.pmid: 15733656
references.citation: Neurosci Biobehav Rev. 2004 Jan;27(8):729-37
references.pmid: 15019423
references.citation: J Neurophysiol. 1983 Mar;49(3):567-81
references.pmid: 6300350
references.citation: Brain Res. 1983 Dec 12;288(1-2):307-14
references.pmid: 6198027
references.citation: Brain Res. 1986 May 28;374(2):357-61
references.pmid: 3755072
references.citation: J Neurosci. 2009 Mar 4;29(9):2684-94
references.pmid: 19261863
references.citation: Pain. 2008 Jan;134(1-2):174-86
references.pmid: 17533118
references.citation: Proc Natl Acad Sci U S A. 2001 Mar 27;98(7):4259-64
references.pmid: 11259662
references.citation: Clin J Pain. 1997 Sep;13(3):189-96
references.pmid: 9303250
references.citation: Brain Res. 1986 Feb 12;365(1):145-50
references.pmid: 3947980
references.citation: Pain. 1979 Jun;6(3):305-327
references.pmid: 460936
references.citation: J Neurosurg. 2005 Dec;103(6):1030-4
references.pmid: 16381189
references.citation: J Neurosci. 1994 Jul;14(7):4095-108
references.pmid: 8027764
references.citation: J Neurosci. 2002 Apr 1;22(7):2748-52
references.pmid: 11923440
references.citation: Neurosurgery. 1998 Nov;43(5):1103-10
references.pmid: 9802854
references.citation: Prog Brain Res. 1988;77:1-29
references.pmid: 3064163
references.citation: Pain. 2003 Mar;102(1-2):87-95
references.pmid: 12620600
references.citation: Science. 1971 Dec 24;174(4016):1351-4
references.pmid: 5167502
references.citation: Prog Neurobiol. 2002 Apr;66(6):355-474
references.pmid: 12034378
references.citation: Clin Neurosurg. 1989;35:429-47
references.pmid: 2783566
references.citation: J Comp Neurol. 1970 May;139(1):105-14
references.pmid: 5440318
references.citation: Brain Res. 1988 Feb 16;441(1-2):87-97
references.pmid: 3359245
references.citation: Eur J Pain. 2008 Nov;12(8):980-9
references.pmid: 18321740
references.citation: Nat Rev Neurosci. 2004 Jul;5(7):565-75
references.pmid: 15208698
references.citation: Pain. 2003 May;103(1-2):57-64
references.pmid: 12749959
references.citation: Cerebellum. 2008;7(3):252-72
references.pmid: 18418691
references.citation: Anesthesiology. 2000 May;92(5):1257-67
references.pmid: 10781270
references.citation: Suppl Clin Neurophysiol. 2006;58:52-67
references.pmid: 16623322
references.citation: J Comp Neurol. 1985 Aug 22;238(4):401-16
references.pmid: 3840182
references.citation: Neurophysiol Clin. 2000 Oct;30(5):263-88
references.pmid: 11126640
references.citation: J Cereb Blood Flow Metab. 1992 Nov;12(6):900-18
references.pmid: 1400644
references.citation: J Neurophysiol. 2002 Apr;87(4):2205-8
references.pmid: 11929939
references.citation: Med Image Anal. 2001 Jun;5(2):143-56
references.pmid: 11516708
references.citation: Pain. 2003 Jan;101(1-2):167-74
references.pmid: 12507711
references.citation: Science. 2002 Mar 1;295(5560):1737-40
references.pmid: 11834781
references.citation: J Comp Neurol. 2004 Apr 12;471(4):446-61
references.pmid: 15022263
references.citation: Neuroimage. 2004 Apr;21(4):1732-47
references.pmid: 15050594
references.citation: J Neurosci. 2005 Aug 10;25(32):7333-41
references.pmid: 16093383
references.citation: Brain Res. 1985 Jul 29;339(2):285-93
references.pmid: 4027627
references.citation: Proc Natl Acad Sci U S A. 2001 Jan 16;98(2):676-82
references.pmid: 11209064
references.citation: Neuroscience. 1983 May;9(1):95-106
references.pmid: 6877597
references.citation: Neuroimage. 2001 Dec;14(6):1370-86
references.pmid: 11707093
references.citation: J Physiol. 1915 Jul 5;49(5):331-48
references.pmid: 16993299
references.citation: Neuroscience. 1982 Jan;7(1):133-59
references.pmid: 7078723
references.citation: Pain. 2006 Jul;123(1-2):169-78
references.pmid: 16616418
references.citation: Neuroimage. 2003 Oct;20(2):1052-63
references.pmid: 14568475
references.citation: Neuroimage. 2007 Jan 1;34(1):310-21
references.pmid: 17055297
references.citation: Brain Res Bull. 1994;34(3):177-82
references.pmid: 8055346
references.citation: Pain. 2004 Feb;107(3):256-266
references.pmid: 14736588
references.citation: J Clin Neurophysiol. 1997 Jan;14(1):2-31
references.pmid: 9013357
references.citation: Brain Res Brain Res Rev. 1996 Oct;22(3):229-44
references.pmid: 8957561
references.citation: J Neurophysiol. 1997 Jun;77(6):3370-80
references.pmid: 9212281
references.citation: Science. 1977 Jul 8;197(4299):183-6
references.pmid: 301658
references.citation: J Neurosurg. 1980 Apr;52(4):486-93
references.pmid: 6966326
references.citation: Pain. 1978 Aug;5(2):99-113
references.pmid: 693073
references.citation: J Comp Neurol. 1986 Oct 15;252(3):323-47
references.pmid: 3793980
references.citation: J Neurophysiol. 1983 Mar;49(3):582-94
references.pmid: 6300351
references.citation: Pain. 1994 Feb;56(2):217-226
references.pmid: 8008411