The modulation effect of longitudinal acupuncture on resting state functional connectivity in knee osteoarthritis patients

Xiaoyan Chen, Rosa B Spaeth, Sonya G Freeman, Donna Moxley Scarborough, Javeria A Hashmi, Hsiao-Ying Wey, Natalia Egorova, Mark Vangel, Jianren Mao, Ajay D Wasan, Robert R Edwards, Randy L Gollub, Jian Kong, Xiaoyan Chen, Rosa B Spaeth, Sonya G Freeman, Donna Moxley Scarborough, Javeria A Hashmi, Hsiao-Ying Wey, Natalia Egorova, Mark Vangel, Jianren Mao, Ajay D Wasan, Robert R Edwards, Randy L Gollub, Jian Kong

Abstract

Recent advances in brain imaging have contributed to our understanding of the neural activity associated with acupuncture treatment. In this study, we investigated functional connectivity across longitudinal acupuncture treatments in older patients with knee osteoarthritis (OA). Over a period of 4 weeks (six treatments), we collected resting state functional magnetic resonance imaging (fMRI) scans from 30 patients before and after their first, third and sixth treatments. Clinical outcome showed a significantly greater pain subscore on the Knee Injury and Osteoarthritis Outcome Score (KOOS) (indicative of improvement) with verum acupuncture than with sham acupuncture. Independent component analysis (ICA) of the resting state fMRI data showed that the right frontoparietal network (rFPN) and the executive control network (ECN) showed enhanced functional connectivity (FC) with the rostral anterior cingulate cortex/medial prefrontal cortex, a key region in the descending pain modulatory system, in the verum groups as compared to the sham group after treatments. We also found that the rFPN connectivity with the left insula is (1) significantly associated with changes in KOOS pain score after treatments, and (2) significantly enhanced after verum acupuncture treatments as compared to sham treatment. Analysis of the acupuncture needle stimulation scan showed that compared with sham treatment, verum acupuncture activated the left operculum/insula, which also overlaps with findings observed in resting state analysis. Our results suggest that acupuncture may achieve its therapeutic effect on knee OA pain by modulating functional connectivity between the rFPN, ECN and the descending pain modulatory pathway.

Clinical trial number: NCT01079390.

Figures

Fig. 1
Fig. 1
Comparison of the pre-acupuncture scans in treatments 6 and 1. a Connectivity between the right frontoparietal network and the rACC increases more in the verum group than in the sham group. (X = 12) b Results in a controlled for age and duration of pain. c Executive control network showed stronger connectivity with rACC after treatment in the verum group than in the sham group. (X = 4) d Results in c controlled for age and duration of pain. e Sensory-motor network showed reduced connectivity with dACC after real acupuncture treatment compared with sham group. (X = −8) f Results in e controlled for age and duration of pain
Fig. 2
Fig. 2
a Shown in green: after treatment, the increase in functional connectivity between the rFPN and left insula/putamen positively correlated with the change in KOOS pain score. Shown in red: the verum group showed significant increase in connectivity between the rFPN and left insula/putamen compared to sham group. (X = −30) b Results in a after adjusting for age and duration of pain. The comparison between verum and sham shown in red were at a less conservative threshold of voxel-wise Z > 1.96 and a corrected cluster significance threshold of P < 0.05
Fig. 3
Fig. 3
Shown in green: during acupuncture needle stimulation, the left posterior parietal operculum showed more activation in the verum group than in the sham group. Shown in blue: after treatment, the change (increased) in connectivity between the right frontoparietal network and left posterior parietal operculum correlates with the change in KOOS pain in patients (Y = −34)
Fig. 4
Fig. 4
Hypothetical schematic illustration of the resting state functional connectivity modulated by acupuncture and its relevance to pain relief. Note that this diagram does not exhaustively describe all networks and brain regions involved in acupuncture analgesia but only summarizes the mechanisms likely relevant for the current study. Red indicates increased activation/connectivity; blue indicates decreased activation/connectivity. Verum acupuncture needle stimulation activated the operculum/insula, as suggested by the functional MRI analysis. The insula/operculum processes information about both the sensory component of pain (posterior insula), as well as cognitive-emotional aspects of pain (anterior insula) [101]. In its capacity as a nociceptive salience detection, affective and pain decision-making hub [102], it might (1) increase functional connectivity between the attention, cognitive control and appraisal networks (rFPN, ECN) and the rACC/MPFC, which is a key brain region for attention and descending pain modulation with a direct connection to the PAG [75], further inhibiting noxious input; (2) decrease functional connectivity between the SMN and dACC, representing reduced interaction between the sensory and affective components of pain processing, providing further relief from pain

References

    1. Ho-Pham LT, Lai TQ, Mai LD, Doan MC, Pham HN, Nguyen TV. Prevalence of radiographic osteoarthritis of the knee and its relationship to self-reported pain. PLoS One. 2014;9(4):e94563. doi: 10.1371/journal.pone.0094563.
    1. Nguyen US, Zhang Y, Zhu Y, Niu J, Zhang B, Felson DT. Increasing prevalence of knee pain and symptomatic knee osteoarthritis: survey and cohort data. Ann Intern Med. 2011;155(11):725–732. doi: 10.7326/0003-4819-155-11-201112060-00004.
    1. Hochman JR, Davis AM, Elkayam J, Gagliese L, Hawker GA. Neuropathic pain symptoms on the modified painDETECT correlate with signs of central sensitization in knee osteoarthritis. Osteoarthr Cartil. 2013;21(9):1236–1242. doi: 10.1016/j.joca.2013.06.023.
    1. Arendt-Nielsen L, Nie H, Laursen MB, Laursen BS, Madeleine P, Simonsen OH, et al. Sensitization in patients with painful knee osteoarthritis. Pain. 2010;149(3):573–581. doi: 10.1016/j.pain.2010.04.003.
    1. Finan PH, Buenaver LF, Bounds SC, Hussain S, Park RJ, Haque UJ, et al. Discordance between pain and radiographic severity in knee osteoarthritis: findings from quantitative sensory testing of central sensitization. Arthritis Rheum. 2013;65(2):363–372. doi: 10.1002/art.34646.
    1. Gwilym SE, Keltner JR, Warnaby CE, Carr AJ, Chizh B, Chessell I, et al. Psychophysical and functional imaging evidence supporting the presence of central sensitization in a cohort of osteoarthritis patients. Arthritis Rheum. 2009;61(9):1226–1234. doi: 10.1002/art.24837.
    1. Gay MC, Philippot P, Luminet O. Differential effectiveness of psychological interventions for reducing osteoarthritis pain: a comparison of Erikson [correction of Erickson] hypnosis and Jacobson relaxation. Eur J Pain. 2002;6(1):1–16. doi: 10.1053/eujp.2001.0263.
    1. Berman BM, Lao L, Langenberg P, Lee WL, Gilpin AM, Hochberg MC. Effectiveness of acupuncture as adjunctive therapy in osteoarthritis of the knee: a randomized, controlled trial. Ann Intern Med. 2004;141(12):901–910. doi: 10.7326/0003-4819-141-12-200412210-00006.
    1. Felson DT, Lawrence RC, Hochberg MC, McAlindon T, Dieppe PA, Minor MA, et al. Osteoarthritis: new insights. Part 2: treatment approaches. Ann Intern Med. 2000;133(9):726–737. doi: 10.7326/0003-4819-133-9-200011070-00015.
    1. Witt C, Brinkhaus B, Jena S, Linde K, Streng A, Wagenpfeil S, et al. Acupuncture in patients with osteoarthritis of the knee: a randomised trial. Lancet. 2005;366(9480):136–143. doi: 10.1016/S0140-6736(05)66871-7.
    1. Scharf HP, Mansmann U, Streitberger K, Witte S, Kramer J, Maier C, et al. Acupuncture and knee osteoarthritis: a three-armed randomized trial. Ann Intern Med. 2006;145(1):12–20. doi: 10.7326/0003-4819-145-1-200607040-00005.
    1. Mavrommatis CI, Argyra E, Vadalouka A, Vasilakos DG. Acupuncture as an adjunctive therapy to pharmacological treatment in patients with chronic pain due to osteoarthritis of the knee: a 3-armed, randomized, placebo-controlled trial. Pain. 2012;153(8):1720–1726. doi: 10.1016/j.pain.2012.05.005.
    1. Hinman RS, McCrory P, Pirotta M, Relf I, Forbes A, Crossley K, et al. Acupuncture for chronic knee pain a randomized clinical trial. JAMA. 2014;312(13):1313–1322. doi: 10.1001/jama.2014.12660.
    1. Suarez-Almazor M, Looney C, Kiu Y, Cox V, Pietz K, Marcus D, et al. A randomized controlled trial of acupuncture for osteoarthritis of the knee: effects of patient-practitioner communication. Arthritis Care Res. 2010;62:1229–1236. doi: 10.1002/acr.20225.
    1. MacPherson H, Thomas K, Walters S, Fitter M. The York acupuncture safety study: prospective survey of 34 000 treatments by traditional acupuncturists. BMJ. 2001;323(7311):486–487. doi: 10.1136/bmj.323.7311.486.
    1. White A, Hayhoe S, Hart A, Ernst E. Adverse events following acupuncture: prospective survey of 32 000 consultations with doctors and physiotherapists. BMJ. 2001;323(7311):485–486. doi: 10.1136/bmj.323.7311.485.
    1. Melchart D, Weidenhammer W, Streng A, Reitmayr S, Hoppe A, Ernst E, et al. Prospective investigation of adverse effects of acupuncture in 97 733 patients. Arch Intern Med. 2004;164(1):104–105. doi: 10.1001/archinte.164.1.104.
    1. Ochi JW. Acupuncture instead of codeine for tonsillectomy pain in children. Int J Pediatr Otorhinolaryngol. 2013;77(12):2058–2062. doi: 10.1016/j.ijporl.2013.10.008.
    1. Han JS. Acupuncture analgesia: areas of consensus and controversy. Pain. 2011;152(3 Suppl):S41–S48. doi: 10.1016/j.pain.2010.10.012.
    1. Hans JS. Physiology of acupuncture: review of thirty years of research. J Altern Complement Med. 1997;(Suppl 1):S101–8.
    1. Zhao ZQ. Neural mechanism underlying acupuncture analgesia. Prog Neurobiol. 2008;85(4):355–375. doi: 10.1016/j.pneurobio.2008.05.004.
    1. Dougherty DD, Kong J, Webb M, Bonab AA, Fischman AJ, Gollub RL. A combined [11C]diprenorphine PET study and fMRI study of acupuncture analgesia. Behav Brain Res. 2008;193(1):63–8 (PMCID: PMC2538486).
    1. Chae Y, Chang DS, Lee SH, Jung WM, Lee IS, Jackson S, et al. Inserting needles into the body: a meta-analysis of brain activity associated with acupuncture needle stimulation. J Pain. 2013;14(3):215–222. doi: 10.1016/j.jpain.2012.11.011.
    1. Huang W, Pach D, Napadow V, Park K, Long X, Neumann J, et al. Characterizing acupuncture stimuli using brain imaging with FMRI—a systematic review and meta-analysis of the literature. PLoS One. 2012;7(4):e32960. doi: 10.1371/journal.pone.0032960.
    1. Kong J, Ma L, Gollub RL, Wei J, Yang X, Li D, et al. A pilot study of functional magnetic resonance imaging of the brain during manual and electroacupuncture stimulation of acupuncture point (LI-4 Hegu) in normal subjects reveals differential brain activation between methods. J Altern Complement Med. 2002;8(4):411–419. doi: 10.1089/107555302760253603.
    1. Kong J, Gollub RL, Webb JM, Kong JT, Vangel MG, Kwong K. Test-retest study of fMRI signal change evoked by electroacupuncture stimulation. Neuroimage. 2007;34(3):1171–81 (PMCID: PMC1994822).
    1. Leung A, Zhao Y, Shukla S. The effect of acupuncture needle combination on central pain processing—an fMRI study. Mol Pain. 2014;10:23. doi: 10.1186/1744-8069-10-23.
    1. Zyloney CE, Jensen K, Polich G, Loiotile RE, Cheetham A, LaViolette PS, et al. Imaging the functional connectivity of the Periaqueductal Gray during genuine and sham electroacupuncture treatment. Mol Pain. 2010;6:80. doi: 10.1186/1744-8069-6-80.
    1. Dhond RP, Yeh C, Park K, Kettner N, Napadow V. Acupuncture modulates resting state connectivity in default and sensorimotor brain networks. Pain. 2008;136(3):407–418. doi: 10.1016/j.pain.2008.01.011.
    1. Liu P, Qin W, Zhang Y, Tian J, Bai L, Zhou G, et al. Combining spatial and temporal information to explore function-guide action of acupuncture using fMRI. J Magn Reson Imaging. 2009;30(1):41–46. doi: 10.1002/jmri.21805.
    1. Bai L, Qin W, Tian J, Dong M, Pan X, Chen P, et al. Acupuncture modulates spontaneous activities in the anticorrelated resting brain networks. Brain Res. 2009;1279:37–49. doi: 10.1016/j.brainres.2009.04.056.
    1. Qin W, Tian J, Bai L, Pan X, Yang L, Chen P, et al. FMRI connectivity analysis of acupuncture effects on an amygdala-associated brain network. Mol Pain. 2008;4:55. doi: 10.1186/1744-8069-4-55.
    1. Liu B, Chen J, Wang J, Liu X, Duan X, Shang X, et al. Altered small-world efficiency of brain functional networks in acupuncture at ST36: a functional MRI study. PLoS One. 2012;7(6):e39342. doi: 10.1371/journal.pone.0039342.
    1. Sun R, Yang Y, Li Z, Li Y, Cheng S, Zeng F. Connectomics: a New Direction in Research to Understand the Mechanism of Acupuncture. Evid Based Complement Alternat Med. 2014;2014:568429.
    1. Zhang Y, Qin W, Liu P, Tian J, Liang J, von Deneen KM, et al. An fMRI study of acupuncture using independent component analysis. Neurosci Lett. 2009;449(1):6–9. doi: 10.1016/j.neulet.2008.10.071.
    1. Apkarian AV, Baliki MN, Geha PY. Towards a theory of chronic pain. Prog Neurobiol. 2009;87(2):81–97. doi: 10.1016/j.pneurobio.2008.09.018.
    1. Bushnell MC. How neuroimaging studies have challenged us to rethink: is chronic pain a disease? J Pain. 2009;10(11):1113–1120. doi: 10.1016/j.jpain.2009.09.001.
    1. Davis KD, Moayedi M. Central mechanisms of pain revealed through functional and structural MRI. J Neuroimmune Pharmacol. 2013;8(3):518–534. doi: 10.1007/s11481-012-9386-8.
    1. Baliki MN, Petre B, Torbey S, Herrmann KM, Huang L, Schnitzer TJ et al. Corticostriatal functional connectivity predicts transition to chronic back pain. Nat Neurosci. 2012.doi:10.1038/nn.3153.
    1. Loggia ML, Kim J, Gollub RL, Vangel MG, Kirsch I, Kong J, et al. Default mode network connectivity encodes clinical pain: an arterial spin labeling study. Pain. 2013;154:24–33. doi: 10.1016/j.pain.2012.07.029.
    1. Kong J, Spaech R, Wey HY, Cheetham A, Cook A, Jensen K et al. S1 is associated with chronic low back pain: a functional and structural MRI study. Molecular pain. 2013;9(43):doi:10.1186/744-8069-9-43.
    1. Niesters M, Khalili-Mahani N, Martini C, Aarts L, van Gerven J, van Buchem MA, et al. Effect of subanesthetic ketamine on intrinsic functional brain connectivity: a placebo-controlled functional magnetic resonance imaging study in healthy male volunteers. Anesthesiology. 2012;117(4):868–877. doi: 10.1097/ALN.0b013e31826a0db3.
    1. Harris RE, Napadow V, Huggins JP, Pauer L, Kim J, Hampson J, et al. Pregabalin rectifies aberrant brain chemistry, connectivity, and functional response in chronic pain patients. Anesthesiology. 2013;119(6):1453–1464. doi: 10.1097/ALN.0000000000000017.
    1. Roos EM, Toksvig-Larsen S. Knee injury and Osteoarthritis Outcome Score (KOOS) – validation and comparison to the WOMAC in total knee replacement. Health Quality Life Outcomes. 2003;1(17):1–10.
    1. Spaeth RB, Camhi S, Hashmi JA, Vangel M, Wasan AD, Edwards RR, et al. A longitudinal study of the reliability of acupuncture deqi sensations in knee osteoarthritis. Evid Based Complement Alternat Med. 2013;2013:204259.
    1. Kong J, Gollub R, Huang T, Polich G, Napadow V, Hui K, et al. Acupuncture de qi, from qualitative history to quantitative measurement. J Altern Complement Med. 2007;13(10):1059–1070. doi: 10.1089/acm.2007.0524.
    1. Kong J, Jensen K, Loiotile R, Cheetham A, Wey HY, Tan T, et al. Functional connectivity of frontoparietal network predicts cognitive modulation of pain. Pain. 2013;154(3):459–467. doi: 10.1016/j.pain.2012.12.004.
    1. Biswal BB, Mennes M, Zuo XN, Gohel S, Kelly C, Smith SM, et al. Toward discovery science of human brain function. Proc Natl Acad Sci USA. 2010;107(10):4734–4739. doi: 10.1073/pnas.0911855107.
    1. Goldin PR, Ziv M, Jazaieri H, Hahn K, Heimberg R, Gross JJ. Impact of cognitive behavioral therapy for social anxiety disorder on the neural dynamics of cognitive reappraisal of negative self-beliefs: randomized clinical trial. JAMA Psychiatry. 2013;70(10):1048–1056. doi: 10.1001/jamapsychiatry.2013.234.
    1. Pavuluri MN, Ellis JA, Wegbreit E, Passarotti AM, Stevens MC. Pharmacotherapy impacts functional connectivity among affective circuits during response inhibition in pediatric mania. Behav Brain Res. 2012;226(2):493–503. doi: 10.1016/j.bbr.2011.10.003.
    1. Fang J, Rong P, Hong Y, Fan Y, Liu J, Wang H, et al. Transcutaneous vagus nerve stimulation modulates default mode network in major depressive disorder. Biol Psychiatry. 2015
    1. Apkarian AV, Bushnell MC, Treede RD, Zubieta JK. Human brain mechanisms of pain perception and regulation in health and disease. Eur J Pain. 2005;9(4):463–484. doi: 10.1016/j.ejpain.2004.11.001.
    1. Tracey I, Mantyh PW. The cerebral signature for pain perception and its modulation. Neuron. 2007;55(3):377–391. doi: 10.1016/j.neuron.2007.07.012.
    1. Kong J, Gollub RL, Rosman IS, Webb JM, Vangel MG, Kirsch I, et al. Brain activity associated with expectancy-enhanced placebo analgesia as measured by functional magnetic resonance imaging. J Neurosci. 2006;26(2):381–388. doi: 10.1523/JNEUROSCI.3556-05.2006.
    1. Kong J, Loggia ML, Zyloney C, Tu P, Laviolette P, Gollub RL. Exploring the brain in pain: activations, deactivations and their relation. Pain. 2010;148:257–267. doi: 10.1016/j.pain.2009.11.008.
    1. Smith SM, Fox PT, Miller KL, Glahn DC, Fox PM, Mackay CE, et al. Correspondence of the brain’s functional architecture during activation and rest. Proc Natl Acad Sci USA. 2009;106(31):13040–13045. doi: 10.1073/pnas.0905267106.
    1. Downar J, Crawley AP, Mikulis DJ, Davis KD. A multimodal cortical network for the detection of changes in the sensory environment. Nat Neurosci. 2000;3(3):277–283. doi: 10.1038/72991.
    1. Vincent JL, Kahn I, Snyder AZ, Raichle ME, Buckner RL. Evidence for a frontoparietal control system revealed by intrinsic functional connectivity. J Neurophysiol. 2008;100(6):3328–3342. doi: 10.1152/jn.90355.2008.
    1. Mayer EA, Berman S, Suyenobu B, Labus J, Mandelkern MA, Naliboff BD, et al. Differences in brain responses to visceral pain between patients with irritable bowel syndrome and ulcerative colitis. Pain. 2005;115(3):398–409. doi: 10.1016/j.pain.2005.03.023.
    1. Kong J, Kaptchuk TJ, Polich G, Kirsch I, Gollub RL. Placebo analgesia: findings from brain imaging studies and emerging hypotheses. Rev Neurosci. 2007;18(3–4):173–190.
    1. Goldman-Rakic PS. Topography of cognition: parallel distributed networks in primate association cortex. Annu Rev Neurosci. 1988;11:137–156. doi: 10.1146/annurev.ne.11.030188.001033.
    1. Parks EL, Geha PY, Baliki MN, Katz J, Schnitzer TJ, Apkarian AV. Brain activity for chronic knee osteoarthritis: dissociating evoked pain from spontaneous pain. Eur J Pain. 2011;15(8):843 e1–14. doi:10.1016/j.ejpain.2010.12.007.
    1. Howard MA, Sanders D, Krause K, O’Muircheartaigh J, Fotopoulou A, Zelaya F, et al. Alterations in resting-state regional cerebral blood flow demonstrate ongoing pain in osteoarthritis: an arterial spin-labeled magnetic resonance imaging study. Arthritis Rheum. 2012;64(12):3936–3946. doi: 10.1002/art.37685.
    1. Miller EK. The prefrontal cortex and cognitive control. Nat Rev Neurosci. 2000;1(1):59–65. doi: 10.1038/35036228.
    1. Corbetta M, Shulman GL. Control of goal-directed and stimulus-driven attention in the brain. Nat Rev Neurosci. 2002;3(3):201–215. doi: 10.1038/nrn755.
    1. Ridderinkhof KR, Ullsperger M, Crone EA, Nieuwenhuis S. The role of the medial frontal cortex in cognitive control. Science. 2004;306(5695):443–447. doi: 10.1126/science.1100301.
    1. Matsumoto K, Tanaka K. Neuroscience. Conflict and cognitive control. Science. 2004;303(5660):969–970. doi: 10.1126/science.1094733.
    1. Carter CS, van Veen V. Anterior cingulate cortex and conflict detection: an update of theory and data. Cogn Affect Behav Neurosci. 2007;7(4):367–379. doi: 10.3758/CABN.7.4.367.
    1. Crone EA, Wendelken C, Donohue SE, Bunge SA. Neural evidence for dissociable components of task-switching. Cereb Cortex. 2006;16(4):475–486. doi: 10.1093/cercor/bhi127.
    1. Fields H. State-dependent opioid control of pain. Nat Rev Neurosci. 2004;5(7):565–575. doi: 10.1038/nrn1431.
    1. Tracey I, Ploghaus A, Gati JS, Clare S, Smith S, Menon RS, et al. Imaging attentional modulation of pain in the periaqueductal gray in humans. J Neurosci. 2002;22(7):2748–2752.
    1. Jensen KB, Loitoile R, Kosek E, Petzke F, Carville S, Fransson P, et al. Patients with fibromyalgia display less functional connectivity in the brain’s pain inhibitory network. Mol Pain. 2012;8(1):32. doi: 10.1186/1744-8069-8-32.
    1. Yu R, Gollub R, Spaetha R, Napadowa V, Wasana A, Kong J. Disrupted functional connectivity of the periaqueductal gray in chronic low back pain. NeuroImage. 2014;6:100–8.
    1. Eippert F, Bingel U, Schoell ED, Yacubian J, Klinger R, Lorenz J, et al. Activation of the opioidergic descending pain control system underlies placebo analgesia. Neuron. 2009;63(4):533–543. doi: 10.1016/j.neuron.2009.07.014.
    1. Kong J, Tu PC, Zyloney C, Su TP. Intrinsic functional connectivity of the periaqueductal gray, a resting fMRI study. Behav Brain Res. 2010;211(2):215–219. doi: 10.1016/j.bbr.2010.03.042.
    1. Kucyi A, Salomons TV, Davis KD. Mind wandering away from pain dynamically engages antinociceptive and default mode brain networks. Proc Natl Acad Sci USA. 2013;110(46):18692–18697. doi: 10.1073/pnas.1312902110.
    1. Salomons TV, Johnstone T, Backonja MM, Davidson RJ. Perceived controllability modulates the neural response to pain. J Neurosci. 2004;24:7199–7203. doi: 10.1523/JNEUROSCI.1315-04.2004.
    1. Egorova N, Gollub R, J K. Repeated verum but not placebo acupuncture normalizes connectivity in brain regions dysregulated in chronic pain. NeuroImage. 2015. doi:10.1016/j.nicl.2015.09.012.
    1. Chen XY, Spaeth RB, Retzepi K, Ott D, Kong J. Acupuncture modulates cortical thickness and functional connectivity in knee osteoarthritis patients. Sci Rep 2014;4(6482). doi:10.1038/srep06482.
    1. Rainville P, Duncan GH, Price DD, Carrier B, Bushnell MC. Pain affect encoded in human anterior cingulate but not somatosensory cortex. Science. 1997;277:968–971. doi: 10.1126/science.277.5328.968.
    1. Price DD. Psychological and neural mechanisms of the affective dimension of pain. Science. 2000;288:1769–1772. doi: 10.1126/science.288.5472.1769.
    1. Kong J, Gollub RL, Polich G, Kirsch I, Laviolette P, Vangel M et al. A functional magnetic resonance imaging study on the neural mechanisms of hyperalgesic nocebo effect. J Neurosci. 2008;28(49):13354–62 (PMCID: PMC2649754).
    1. Zhang Y, Meng X, Li A, Xin J, Berman BM, Lao L, et al. Electroacupuncture alleviates affective pain in an inflammatory pain rat model. Eur J Pain. 2012;16(2):170–181. doi: 10.1016/j.ejpain.2011.07.002.
    1. Fang J, Jin Z, Wang Y, Li K, Kong J, Nixon EE, et al. The salient characteristics of the central effects of acupuncture needling: limbic-paralimbic-neocortical network modulation. Hum Brain Mapp. 2009;30(4):1196–1206. doi: 10.1002/hbm.20583.
    1. Qin W, Bai L, Dai J, Liu P, Dong M, Liu J, et al. The temporal-spatial encoding of acupuncture effects in the brain. Mol Pain. 2011;7:19. doi: 10.1186/1744-8069-7-19.
    1. Kong J, Ma L, Gollub RL, Wei J, Yang X, Li D, et al. A pilot study of functional magnetic resonance imaging of the brain during manual and electroacupuncture stimulation of acupuncture point (LI-4 Hegu) in normal subjects reveals differential brain activation between methods. J Altern Complement Med. 2002;8(4):411–419. doi: 10.1089/107555302760253603.
    1. Pariente J, White P, Frackowiak RS, Lewith G. Expectancy and belief modulate the neuronal substrates of pain treated by acupuncture. Neuroimage. 2005;25(4):1161–1167. doi: 10.1016/j.neuroimage.2005.01.016.
    1. Eickhoff SB, Schleicher A, Zilles K, Amunts K. The human parietal operculum. I. Cytoarchitectonic mapping of subdivisions. Cereb Cortex. 2006;16(2):254–267. doi: 10.1093/cercor/bhi105.
    1. Menon V, Uddin LQ. Saliency, switching, attention and control: a network model of insula function. Brain Struct Funct. 2010;214(5–6):655–667. doi: 10.1007/s00429-010-0262-0.
    1. Melzack R. Folk Medicine and the sensory modulation of pain. In: Wall PD, Melzack R, editors. Textbook of Pain. London: Churchill Livingstone; 1994. pp. 1209–1217.
    1. Dumville J, Hahn S, Miles J, Torgerson D. The use of unequal randomisation ratios in clinical trials: a review. Contemp Clin Trials. 2006;27:1–12. doi: 10.1016/j.cct.2005.08.003.
    1. Streitberger K, Kleinhenz J. Introducing a placebo needle into acupuncture research. Lancet. 1998;352:364–365. doi: 10.1016/S0140-6736(97)10471-8.
    1. Kong J, Fufa DT, Gerber AJ, Rosman IS, Vangel MG, Gracely RH, et al. Psychophysical outcomes from a randomized pilot study of manual, electro, and sham acupuncture treatment on experimentally induced thermal pain. J Pain. 2005;6(1):55–64. doi: 10.1016/j.jpain.2004.10.005.
    1. Zhu D, Gao Y, Chang J, Kong J. Placebo acupuncture devices: considerations for acupuncture research. Evid Based Complement Alternat Med. 2013;2013:628907.
    1. Smith SM, Jenkinson M, Woolrich MW, Beckmann CF, Behrens TE, Johansen-Berg H, et al. Advances in functional and structural MR image analysis and implementation as FSL. Neuroimage. 2004;23(Suppl 1):S208–S219. doi: 10.1016/j.neuroimage.2004.07.051.
    1. Beckmann CF, Smith SM. Probabilistic independent component analysis for functional magnetic resonance imaging. IEEE Trans Med Imaging. 2004;23(2):137–152. doi: 10.1109/TMI.2003.822821.
    1. Xue T, Yuan K, Zhao L, Yu D, Dong T, Cheng P, et al. Intrinsic brain network abnormalities in migraines without aura revealed in resting-state fMRI. PLoS One. 2012;7(12):e52927. doi: 10.1371/journal.pone.0052927.
    1. Russo A, Tessitore A, Giordano A, Corbo D, Marcuccio L, De Stefano M, et al. Executive resting-state network connectivity in migraine without aura. Cephalalgia. 2012;32(14):1041–1048. doi: 10.1177/0333102412457089.
    1. Bai L, Qin W, Tian J, Liu P, Li L, Chen P, et al. Time-varied characteristics of acupuncture effects in fMRI studies. Hum Brain Mapp. 2009;30(11):3445–3460. doi: 10.1002/hbm.20769.
    1. Bai L, Tian J, Zhong C, Xue T, You Y, Liu Z, et al. Acupuncture modulates temporal neural responses in wide brain networks: evidence from fMRI study. Mol Pain. 2010;6:73. doi: 10.1186/1744-8069-6-73.
    1. Wiech K, Jbabdi S, Lin CS, Andersson J, Tracey I. Differential structural and resting state connectivity between insular subdivisions and other pain-related brain regions. Pain. 2014;155(10):2047–2055. doi: 10.1016/j.pain.2014.07.009.
    1. Wiech K, Lin CS, Brodersen KH, Bingel U, Ploner M, Tracey I. Anterior insula integrates information about salience into perceptual decisions about pain. J Neurosci. 2010;30(48):16324–16331. doi: 10.1523/JNEUROSCI.2087-10.2010.

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa