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Pain Management Volume 1, 2011 - Issue 6
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Review

The Brain in Chronic Pain: Clinical Implications

A Vania Apkarian† Northwestern University, Feinberg School of Medicine, Department of Physiology, 303 E Chicago Avenue, Chicago, IL60610, USA. Correspondence[email protected]
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Pages 577-586 | Published online: 02 Nov 2011

Bibliography

  • Bennett GJ , XieYK. A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain33(1) , 87–107 (1988).
  • Basbaum AI , BautistaDM, ScherrerG, JuliusD. Cellular and molecular mechanisms of pain. Cell139(2) , 267–284 (2009).
  • Costigan M , ScholzJ, WoolfCJ. Neuropathic pain: a maladaptive response of the nervous system to damage. Annu. Rev. Neurosci.32 , 1–32 (2009).
  • Latremoliere A , WoolfCJ. Central sensitization: a generator of pain hypersensitivity by central neural plasticity. J. Pain10(9) , 895–926 (2009).
  • Apkarian AV , SteaRA, ManglosSH, SzeverenyiNM, KingRB, ThomasFD. Persistent pain inhibits contralateral somatosensory cortical activity in humans. Neurosci. Lett.140(2) , 141–147 (1992).
  • Talbot JD , MarrettS, EvansAC, MeyerE, BushnellMC, DuncanGH. Multiple representations of pain in human cerebral cortex. Science251(4999) , 1355–1358 (1991).
  • Jones AK , BrownWD, FristonKJ, QiLY, FrackowiakRS. Cortical and subcortical localization of response to pain in man using positron emission tomography. Proc. R. Soc. Lond. B. Biol. Sci.244(1309) , 39–44 (1991).
  • Apkarian AV . Pain perception in relation to emotional learning. Curr. Opin. Neurobiol.18(4) , 464–468 (2008).
  • Apkarian AV , BalikiMN, GehaPY. Towards a theory of chronic pain. Prog. Neurobiol.87(2) , 81–97 (2009).
  • Apkarian AV , BushnellMC, TreedeRD, ZubietaJK. Human brain mechanisms of pain perception and regulation in health and disease. Eur. J. Pain9(4) , 463–484 (2005).
  • Apkarian AV , HashmiJA, BalikiMN. Pain and the brain: Specificity and plasticity of the brain in clinical chronic pain. Pain152(3) , S49–S64 (2011).
  • Tracey I , BushnellMC. How neuroimaging studies have challenged us to rethink: is chronic pain a disease? J. Pain10(11) , 1113–1120 (2009).
  • Bushnell MC , ApkarianAV, McmahonSB, KoltzenburgM. Representation of pain in the brain. In: Textbook of Pain. McMahon S, Koltzenburg M (Eds). Elsevier, UK, 107–124 (2006).
  • Bingel U , TraceyI. Imaging CNS modulation of pain in humans. Physiology (Bethesda)23 , 371–380 (2008).
  • Seminowicz DA , DavisKD. A re-examination of pain-cognition interactions: implications for neuroimaging. Pain130(1–2) , 8–13 (2007).
  • Wiech K , PlonerM, TraceyI. Neurocognitive aspects of pain perception. Trends Cogn. Sci.12(8) , 306–313 (2008).
  • Schwenkreis P , MaierC, TegenthoffM. Functional imaging of central nervous system involvement in complex regional pain syndrome. AJNR Am. J. Neuroradiol.30(7) , 1279–1284 (2009).
  • Grachev ID , FredricksonBE, ApkarianAV. Abnormal brain chemistry in chronic back pain: an in vivo proton magnetic resonance spectroscopy study. Pain89(1) , 7–18 (2000).
  • Weissman-Fogel I , MoayediM, TenenbaumHC, GoldbergMB, FreemanBV, DavisKD. Abnormal cortical activity in patients with temporomandibular disorder evoked by cognitive and emotional tasks. Pain152(2) , 384–396 (2011).
  • Classification of Chronic Pain. Merskey H, Bogduk N (Eds). IASP Press, WA, USA (1994).
  • Baliki MN , GehaPY, ApkarianAV. Parsing pain perception between nociceptive representation and magnitude estimation. J. Neurophysiol.101(2) , 875–887 (2009).
  • Marquand A , HowardM, BrammerM, ChuC, CoenS, Mourao-MirandaJ. Quantitative prediction of subjective pain intensity from whole-brain fMRI data using Gaussian processes. Neuroimage49(3) , 2178–2189 (2010).
  • Baliki MN , GehaPY, FieldsHL, ApkarianAV. Predicting value of pain and analgesia: nucleus accumbens response to noxious stimuli changes in the presence of chronic pain. Neuron66(1) , 149–160 (2010).
  • Fields HL . A motivation-decision model of pain: the role of opioids. In: Proceedings of the 11th World Congress on Pain. Flor H, Kalso E, Dostrovsky JO (Eds). IASP Press, WA, USA, 449–459 (2006).
  • Baliki MN , ChialvoDR, GehaPY et al. Chronic pain and the emotional brain: specific brain activity associated with spontaneous fluctuations of intensity of chronic back pain. J. Neurosci. 26(47) , 12165–12173 (2006).
  • Baliki MN , GehaPY, JabakhanjiR, HardenN, SchnitzerTJ, ApkarianAV. A preliminary fMRI study of analgesic treatment in chronic back pain and knee osteoarthritis. Mol. Pain4 , 47 (2008).
  • Geha PY , BalikiMN, ChialvoDR, HardenRN, PaiceJA, ApkarianAV. Brain activity for spontaneous pain of postherpetic neuralgia and its modulation by lidocaine patch therapy. Pain128(1–2) , 88–100 (2007).
  • Geha PY , BalikiMN, WangX, HardenRN, PaiceJA, ApkarianAV. Brain dynamics for perception of tactile allodynia (touch-induced pain) in postherpetic neuralgia. Pain138(3) , 641–656 (2008).
  • Parks EL , GehaPY, BalikiMN, KatzJ, SchnitzerTJ, ApkarianAV. Brain activity for chronic knee osteoarthritis: dissociating evoked pain from spontaneous pain. Eur. J. Pain15(8) , 843.E1–843.E14 (2011).
  • Mayer EA , AzizQ, CoenS et al. Brain imaging approaches to the study of functional GI disorders: a Rome working team report. Neurogastroenterol. Motil. 21(6) , 579–596 (2009).
  • Baliki MN , GehaPY, ApkarianAV, ChialvoDR. Beyond feeling: chronic pain hurts the brain, disrupting the default-mode network dynamics. J. Neurosci.28(6) , 1398–1403 (2008).
  • Napadow V , LacountL, ParkK, As-SanieS, ClauwDJ, HarrisRE. Intrinsic brain connectivity in fibromyalgia is associated with chronic pain intensity. Arthritis. Rheum.62(8) , 2545–2555 (2010).
  • Cauda F , D‘AgataF, SaccoK et al. Altered resting state attentional networks in diabetic neuropathic pain. J. Neurol. Neurosurg. Psychiatry. 81(7) , 806–811 (2010).
  • Cauda F , SaccoK, DucaS et al. Altered resting state in diabetic neuropathic pain. PLoS One 4(2) , E4542 (2009).
  • Malinen S , VartiainenN, HlushchukY et al. Aberrant temporal and spatial brain activity during rest in patients with chronic pain. Proc. Natl Acad. Sci. USA 107(14) , 6493–6497 (2010).
  • Apkarian AV , SosaY, SontyS et al. Chronic back pain is associated with decreased prefrontal and thalamic gray matter density. J. Neurosci. 24 , 10410–10415 (2004).
  • Tu CH , NiddamDM, ChaoHT et al. Brain morphological changes associated with cyclic menstrual pain. Pain 150(3) , 462–468 (2010).
  • Ruscheweyh R , DeppeM, LohmannH et al. Pain is associated with regional gray matter reduction in the general population. Pain 152(4) , 904–911 (2011).
  • May A . Chronic pain may change the structure of the brain. Pain137(1) , 7–15 (2008).
  • Gwilym SE , FillipiniN, DouaudG, CarrAJ, TraceyI. Thalamic atrophy associated with painful osteoarthritis of the hip is reversible after arthroplasty; a longitudinal voxel-based-morphometric study. Arthritis Rheum.62(10) , 2930–2940 (2010).
  • Rodriguez-Raecke R , NiemeierA, IhleK, RuetherW, MayA. Brain gray matter decrease in chronic pain is the consequence and not the cause of pain. J. Neurosci.29(44) , 13746–13750 (2009).
  • Obermann M , NebelK, SchumannC et al. Gray matter changes related to chronic posttraumatic headache. Neurology 73(12) , 978–983 (2009).
  • Seminowicz DA , WidemanTH, NasoL et al. Effective treatment of chronic low back pain in humans reverses abnormal brain anatomy and function. J. Neurosci. 31(20) , 7540–7550 (2011).
  • Lebel A , BecerraL, WallinD et al. fMRI reveals distinct CNS processing during symptomatic and recovered complex regional pain syndrome in children. Brain 131(Pt 7) , 1854–1879 (2008).
  • Seminowicz DA , LaferriereAL, MillecampsM, YuJS, CoderreTJ, BushnellMC. MRI structural brain changes associated with sensory and emotional function in a rat model of long-term neuropathic pain. Neuroimage47(3) , 1007–1014 (2009).
  • Metz AE , YauHJ, CentenoMV, ApkarianAV, MartinaM. Morphological and functional reorganization of rat medial prefrontal cortex in neuropathic pain. Proc. Natl Acad. Sci. USA106(7) , 2423–2428 (2009).
  • Geha PY , BalikiMN, HardenRN, BauerWR, ParrishTB, ApkarianAV. The brain in chronic CRPS pain; abnormal gray–white matter interactions in emotional and autonomic regions. Neuron60(4) , 570–581 (2008).
  • Farmer MA , ChandaML, ParksEL, BalikiMN, ApkarianAV, SchaefferAJ. Brain functional and anatomical changes in chronic prostatitis/chronic pelvic pain syndrome. J. Urol.186(1) , 117–124 (2011).
  • Flor H , ElbertT, KnechtS et al. Phantom-limb pain as a perceptual correlate of cortical reorganization following arm amputation. Nature 375(6531) , 482–484 (1995).
  • Pleger B , RagertP, SchwenkreisP et al. Patterns of cortical reorganization parallel impaired tactile discrimination and pain intensity in complex regional pain syndrome. Neuroimage 32(2) , 503–510 (2006).
  • Maihofner C , BaronR, DecolR et al. The motor system shows adaptive changes in complex regional pain syndrome. Brain 130(Pt 10) , 2671–2687 (2007).
  • Maihofner C , HandwerkerHO, NeundorferB, BirkleinF. Patterns of cortical reorganization in complex regional pain syndrome. Neurology61(12) , 1707–1715 (2003).
  • Freund W , WunderlichAP, StuberG et al. Different activation of opercular and posterior cingulate cortex (PCC) in patients with complex regional pain syndrome (CRPS I) compared with healthy controls during perception of electrically induced pain: a functional MRI study. Clin. J. Pain 26(4) , 339–347 (2010).
  • Olesen SS , FrokjaerJB, LelicD, ValerianiM, DrewesAM. Pain-associated adaptive cortical reorganisation in chronic pancreatitis. Pancreatology10(6) , 742–751 (2011).
  • Zimmerman ME , PanJW, HetheringtonHP, LiptonML, BaigiK, LiptonRB. Hippocampal correlates of pain in healthy elderly adults: a pilot study. Neurology73(19) , 1567–1570 (2009).
  • Emad Y , RagabY, ZeinhomF, El-KhoulyG, Abou-ZeidA, RaskerJJ. Hippocampus dysfunction may explain symptoms of fibromyalgia syndrome. A study with single-voxel magnetic resonance spectroscopy. J. Rheumatol.35(7) , 1371–1377 (2008).
  • Wood PB , PattersonJC 2nd, Sunderland JJ, Tainter KH, Glabus MF, Lilien DL. Reduced presynaptic dopamine activity in fibromyalgia syndrome demonstrated with positron emission tomography: a pilot study. J. Pain8(1) , 51–58 (2007).
  • Fayed N , Garcia-CampayoJ, MagallonR et al. Localized 1H-NMR spectroscopy in patients with fibromyalgia: a controlled study of changes in cerebral glutamate/glutamine, inositol, choline, and N-acetylaspartate. Arthritis Res. Ther. 12(4) , R134 (2011).
  • Fregni F , PotvinK, DasilvaD et al. Clinical effects and brain metabolic correlates in noninvasive cortical neuromodulation for visceral pain. Eur. J. Pain 15(1) , 53–60 (2011).
  • Gussew A , RzannyR, GullmarD, ScholleHC, ReichenbachJR. 1H-MR spectroscopic detection of metabolic changes in pain processing brain regions in the presence of nonspecific chronic low back pain. Neuroimage54(2) , 1315–1323 (2011).
  • Rothman DL , BeharKL, HyderF, ShulmanRG. In vivo NMR studies of the glutamate neurotransmitter flux and neuroenergetics: implications for brain function. Annu. Rev. Physiol.65 , 401–427 (2003).
  • Borsook D , BecerraL. Using NMR approaches to drive the search for new CNS therapeutics. Curr. Opin. Investig. Drugs11(7) , 771–778 (2010).
  • George E , BecerraL, UpadhyayJ, SchmidtU, BorsookD. Evaluation of novel drugs using fMRI in early-phase clinical trials: safety monitoring. Drug Discov. Today15(15–16) , 684–689 (2010).
  • Borsook D , BleakmanD, HargreavesR, UpadhyayJ, SchmidtKF, BecerraL. A ‘BOLD‘ experiment in defining the utility of fMRI in drug development. Neuroimage42(2) , 461–466 (2008).
  • Wartolowska K , TraceyI. Neuroimaging as a tool for pain diagnosis and analgesic development. Neurotherapeutics6(4) , 755–760 (2009).
  • Borsook D , MoultonEA, SchmidtKF, BecerraLR. Neuroimaging revolutionizes therapeutic approaches to chronic pain. Mol. Pain3 , 25 (2007).
  • Baliki M , KatzJ, ChialvoDR, ApkarianAV. Single subject pharmacological-MRI (phMRI) study: modulation of brain activity of psoriatic arthritis pain by cyclooxygenase-2 inhibitor. Mol. Pain1 , 32 (2005).
  • Iannetti GD , ZambreanuL, WiseRG et al. Pharmacological modulation of pain-related brain activity during normal and central sensitization states in humans. Proc. Natl Acad. Sci. USA 102(50) , 18195–18200 (2005).
  • Rogers R , WiseRG, PainterDJ, LongeSE, TraceyI. An investigation to dissociate the analgesic and anesthetic properties of ketamine using functional magnetic resonance imaging. Anesthesiology100(2) , 292–301 (2004).
  • Schweinhardt P , BountraC, TraceyI. Pharmacological FMRI in the development of new analgesic compounds. NMR Biomed.19(6) , 702–711 (2006).
  • Wise RG , RogersR, PainterD et al. Combining fMRI with a pharmacokinetic model to determine which brain areas activated by painful stimulation are specifically modulated by remifentanil. Neuroimage 16(4) , 999–1014 (2002).
  • Wise RG , WilliamsP, TraceyI. Using fMRI to quantify the time dependence of remifentanil analgesia in the human brain. Neuropsychopharmacology29(3) , 626–635 (2004).
  • Negus SS , VanderahTW, BrandtMR, BilskyEJ, BecerraL, BorsookD. Preclinical assessment of candidate analgesic drugs: recent advances and future challenges. J. Pharmacol. Exp. Ther.319(2) , 507–514 (2006).
  • Hess A , AxmannR, RechJ et al. Blockade of TNF-α rapidly inhibits pain responses in the central nervous system. Proc. Natl Acad. Sci. USA 108(9) , 3731–3736 (2011).
  • Takemura Y , YamashitaA, HoriuchiH et al. Effects of gabapentin on brain hyperactivity related to pain and sleep disturbance under a neuropathic pain-like state using fMRI and brain wave analysis. Synapse 65(7) , 668–676 (2011).
  • Sharif-Naeini R , BasbaumAI. Targeting pain where it resides … In the brain. Sci. Transl. Med.3(65) , 65PS61 (2011).
  • Wang H , XuH, WuLJ et al. Identification of an adenylyl cyclase inhibitor for treating neuropathic and inflammatory pain. Sci. Transl. Med. 3(65) , 65RA63 (2011).
  • Li XY , KoHG, ChenT et al. Alleviating neuropathic pain hypersensitivity by inhibiting PKMzeta in the anterior cingulate cortex. Science 330(6009) , 1400–1404 (2010).
  • Millecamps M , CentenoMV, BerraHH et al. D-cycloserine reduces neuropathic pain behavior through limbic NMDA-mediated circuitry. Pain 132(1–2) , 108–123 (2006).
  • Centeno MV , MutsoA, MillecampsM, ApkarianAV. Prefrontal cortex and spinal cord mediated antineuropathy and analgesia induced by sarcosine, a glycine-T1 transpoter inhibitor. Pain145(1–2) , 176–183 (2009).
  • Chappell AS , DesaiahD, Liu-SeifertH et al. A double-blind, randomized, placebo-controlled study of the efficacy and safety of duloxetine for the treatment of chronic pain due to osteoarthritis of the knee. Pain Pract. 11(1) , 33–41 (2011).
  • Kerns RD , SellingerJ, GoodinBR. Psychological treatment of chronic pain. Annu. Rev. Clin. Psychol.7 , 411–434 (2011).

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