title: Clinical effects and brain metabolic correlates in non-invasive cortical neuromodulation for visceral pain.
abstract: OBJECTIVE
  Chronic visceral pain is frequent, extremely debilitating, and generally resistant to pharmacological treatment. It has been shown that chronic visceral inflammation, through altered afferent visceral sensory input, leads to plastic changes in the central nervous system that ultimately sustain pain. Therefore approaches aiming at modulation of brain activity are attractive candidates to control visceral pain.
  
  
  METHODS
  Here we report findings of a phase II, sham-controlled clinical trial assessing the clinical effects and brain metabolic correlates of a 10-day course of daily sessions of slow-frequency, repetitive transcranial magnetic stimulation (rTMS) targeting the right secondary somatosensory cortex (SII) in patients with chronic pancreatitis and severe visceral pain.
  
  
  RESULTS
  Our results show a significant reduction in pain after real rTMS that lasted for at least 3 weeks following treatment. These clinical changes were correlated with increases in glutamate and N-acetyl aspartate (NAA) levels--neurometabolites associated with cortical activity and brain damage--as measured by in vivo single-voxel proton magnetic resonance spectroscopy (1H-MRS). Adverse effects in the real rTMS group were mild and short-lasting.
  
  
  CONCLUSIONS
  Our results support preliminary findings showing that modulation of right SII with rTMS is associated with a significant analgesic effect and that this effect is correlated with an increase in excitatory neurotransmitter levels such as glutamate and NAA.
authors.affiliation: Berenson-Allen Center for Noninvasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA. ffregni@bidmc.harvard.edu
authors.forename: Felipe
authors.initials: F
authors.lastname: Fregni
authors.forename: Kimberly
authors.initials: K
authors.lastname: Potvin
authors.forename: Deborah
authors.initials: D
authors.lastname: Dasilva
authors.forename: Xiaoen
authors.initials: X
authors.lastname: Wang
authors.forename: Robert E
authors.initials: RE
authors.lastname: Lenkinski
authors.forename: Steven D
authors.initials: SD
authors.lastname: Freedman
authors.forename: Alvaro
authors.initials: A
authors.lastname: Pascual-Leone
mesh_terms: D000328:Adult; D000698:Analgesia / Q000379:methods*; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002908:Chronic Disease; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000209:etiology / Q000503:physiopathology; D059408:Pain Management; D050500:Pancreatitis, Chronic / Q000150:complications / Q000503:physiopathology*; D011877:Radionuclide Imaging; D012720:Severity of Illness Index; D013003:Somatosensory Cortex / Q000000981:diagnostic imaging / Q000378:metabolism; D050781:Transcranial Magnetic Stimulation / Q000379:methods; D016896:Treatment Outcome
chemical_list: D001224:Aspartic Acid; D018698:Glutamic Acid; C000179:N-acetylaspartate
references.citation: J Neurophysiol. 2008 May;99(5):2725-30
references.pmid: 18337360
references.citation: Pain. 2006 Dec 15;126(1-3):79-90
references.pmid: 16846694
references.citation: Clin Neurophysiol. 2006 Feb;117(2):455-71
references.pmid: 16387549
references.citation: J Physiol. 2005 Jun 1;565(Pt 2):659-65
references.pmid: 15760946
references.citation: Neurology. 2008 Jun 10;70(24):2329-37
references.pmid: 18541887
references.citation: J Nutr. 2001 Sep;131(9 Suppl):2498S-504S; discussion 2523S-4S
references.pmid: 11533301
references.citation: Anat Rec. 2001 Apr;265(2):54-84
references.pmid: 11323770
references.citation: Ann Neurol. 2005 Dec;58(6):971-2
references.pmid: 16315281
references.citation: Clin Neurophysiol. 2001 Oct;112(10):1781-92
references.pmid: 11595135
references.citation: J Neurol Neurosurg Psychiatry. 2005 Jun;76(6):833-8
references.pmid: 15897507
references.citation: Lancet. 1994 May 7;343(8906):1161
references.pmid: 7910249
references.citation: Am J Physiol Gastrointest Liver Physiol. 2008 Apr;294(4):G918-27
references.pmid: 18258793
references.citation: J Psychiatr Res. 2007 Oct;41(7):606-15
references.pmid: 16600298
references.citation: Clin Neurophysiol. 2006 Jun;117(6):1217-27
references.pmid: 16644277
references.citation: Eur J Neurosci. 1999 Jan;11(1):305-15
references.pmid: 9987033
references.citation: Arch Neurol. 1998 Aug;55(8):1081-8
references.pmid: 9708958
references.citation: AJNR Am J Neuroradiol. 2002 Jun-Jul;23(6):901-5
references.pmid: 12063213
references.citation: Neurology. 1997 May;48(5):1398-403
references.pmid: 9153480
references.citation: J Neurol Neurosurg Psychiatry. 2004 Apr;75(4):612-6
references.pmid: 15026508
references.citation: Prog Neurobiol. 1995 Aug;46(5):531-40
references.pmid: 8532851
references.citation: J Neurosci. 2000 Apr 1;20(7):2657-63
references.pmid: 10729346
references.citation: Can J Neurol Sci. 2008 Nov;35(5):630-7
references.pmid: 19235448
references.citation: J Pain. 2008 Mar;9(3):193-9
references.pmid: 18096437
references.citation: J Neurosci. 2004 Mar 31;24(13):3379-85
references.pmid: 15056717
references.citation: Exp Brain Res. 2005 May;163(1):1-12
references.pmid: 15688174
references.citation: Neuroimage. 2009 Oct 1;47(4):1579-89
references.pmid: 19501172
references.citation: Gastroenterology. 2007 Apr;132(4):1546-56
references.pmid: 17408654
references.citation: J Comp Neurol. 1998 Dec 28;402(4):538-59
references.pmid: 9862325
references.citation: Clin Neurophysiol. 2000 May;111(5):800-5
references.pmid: 10802449
references.citation: Gastroenterology. 1997 Jul;113(1):50-9
references.pmid: 9207261
references.citation: J Nucl Med. 1993 Jul;34(7):1101-2
references.pmid: 8315485
references.citation: Surg Endosc. 2001 Jul;15(7):706-9
references.pmid: 11591972
references.citation: Pain. 2006 May;122(1-2):22-7
references.pmid: 16495011
references.citation: Pain. 2008 Sep 15;138(3):546-555
references.pmid: 18367333
references.citation: Am J Surg. 1996 Jan;171(1):142-5; discussion 145-6
references.pmid: 8554129
references.citation: J Neurosci. 2008 Dec 3;28(49):13202-8
references.pmid: 19052211
references.citation: Exp Brain Res. 2007 Feb;176(4):603-15
references.pmid: 16972076
references.citation: Pancreatology. 2007;7(5-6):411-22
references.pmid: 17898531
references.citation: Radiology. 1993 May;187(2):433-7
references.pmid: 8475286
references.citation: J Biol Chem. 2005 Mar 25;280(12):11505-12
references.pmid: 15649886
references.citation: Int J Clin Pharmacol Res. 1997;17(2-3):63-6
references.pmid: 9403356
references.citation: ScientificWorldJournal. 2006 Apr 18;6:472-90
references.pmid: 16633700
references.citation: NMR Biomed. 1991 Apr;4(2):47-52
references.pmid: 1650241
references.citation: Eur J Pain. 2010 Feb;14(2):142-8
references.pmid: 19473859