Functional magnetic resonance imaging (fMRI) changes and saliva production associated with acupuncture at LI-2 acupuncture point: a randomized controlled study

Gary Deng, Bob L Hou, Andrei I Holodny, Barrie R Cassileth, Gary Deng, Bob L Hou, Andrei I Holodny, Barrie R Cassileth

Abstract

Background: Clinical studies suggest that acupuncture can stimulate saliva production and reduce xerostomia (dry mouth). We were interested in exploring the neuronal substrates involved in such responses.

Methods: In a randomized, sham acupuncture controlled, subject blinded trial, twenty healthy volunteers received true and sham acupuncture in random order. Cortical regions that were activated or deactivated during the interventions were evaluated by functional magnetic resonance imaging (fMRI). Saliva production was also measured.

Results: Unilateral manual acupuncture stimulation at LI-2, a point commonly used in clinical practice to treat xerostomia, was associated with bilateral activation of the insula and adjacent operculum. Sham acupuncture at an adjacent site induced neither activation nor deactivation. True acupuncture induced more saliva production than sham acupuncture.

Conclusion: Acupuncture at LI-2 was associated with neuronal activations absent during sham acupuncture stimulation. Neuroimaging signal changes appear correlated to saliva production.

Figures

Figure 1
Figure 1
Experimental Design. Each subjects received both true and sham acupuncture in a randomized order. Boxcar design of fMRI paradigm was used. Each fMRI paradigm lasted a total of 8 minutes and 40 seconds. Stimulation (true or sham acupuncture) was initiated at the time points indicated with the downward arrows and stopped at those indicated with the upward arrows (panel 1a). During true acupuncture, a real acupuncture needle was inserted at the LI-2 acupuncture point. During sham acupuncture, a Streitberger placebo needle was applied at a non-acupuncture (sham) point (panel 1b).
Figure 2
Figure 2
fMRI changes associated with true acupuncture at LI-2. Sagittal, coronal and axial view (respectively) of cortical areas activated by the true acupuncture paradigm.
Figure 3
Figure 3
Specific activation by true acupuncture versus placebo acupuncture. Activation regions shown by fMRI signals associated with true acupuncture were compared to those from sham acupuncture. Panel 3a: sagittal, coronal and axial view (respectively) of activation in the insula and adjacent operculi. Panel 3b: Correlation of saliva production with ROI volumes.
Figure 4
Figure 4
Schematic representation of the gustation-salivation neuronal circuitry and how acupuncture may interact with it. Green lines represent input neural signals, red lines output signals. Solid lines represent physiological response of salivation to gustatory stimuli. Dashed lines represent physiological signals from other cortices. Dotted lines represent the hypothetical pathway through which acupuncture activates the opercular and insular cortices. Areas A: thalamus; B: the insular and opercular cortices; C: salivatory nuclei in the pons.

References

    1. Kaptchuk TJ. Acupuncture: theory, efficacy, and practice. Ann Intern Med. 2002;136:374–83.
    1. Alimi D, Rubino C, Pichard-Leandri E, Fermand-Brule S, Dubreuil-Lemaire ML, Hill C. Analgesic effect of auricular acupuncture for cancer pain: a randomized, blinded, controlled trial. J Clin Oncol. 2003;21:4120–6. doi: 10.1200/JCO.2003.09.011.
    1. Kaptchuk TJ, Stason WB, Davis RB, Legedza AR, Schnyer RN, Kerr CE, Stone DA, Nam BH, Kirsch I, Goldman RH. Sham device v inert pill: randomised controlled trial of two placebo treatments. Bmj. 2006;332:391–7. doi: 10.1136/bmj.38726.603310.55.
    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;141:901–10.
    1. Pariente J, White P, Frackowiak RS, Lewith G. Expectancy and belief modulate the neuronal substrates of pain treated by acupuncture. Neuroimage. 2005;25:1161–7. doi: 10.1016/j.neuroimage.2005.01.016.
    1. Kong J, Gollub RL, Rosman IS, Webb JM, Vangel MG, Kirsch I, Kaptchuk TJ. Brain activity associated with expectancy-enhanced placebo analgesia as measured by functional magnetic resonance imaging. J Neurosci. 2006;26:381–8. doi: 10.1523/JNEUROSCI.3556-05.2006.
    1. Hui KK, Liu J, Makris N, Gollub RL, Chen AJ, Moore CI, Kennedy DN, Rosen BR, Kwong KK. Acupuncture modulates the limbic system and subcortical gray structures of the human brain: evidence from fMRI studies in normal subjects. Hum Brain Mapp. 2000;9:13–25. doi: 10.1002/(SICI)1097-0193(2000)9:1<13::AID-HBM2>;2-F.
    1. Wu MT, Hsieh JC, Xiong J, Yang CF, Pan HB, Chen YC, Tsai G, Rosen BR, Kwong KK. Central nervous pathway for acupuncture stimulation: localization of processing with functional MR imaging of the brain – preliminary experience. Radiology. 1999;212:133–41.
    1. Lewith GT, White PJ, Pariente J. Investigating acupuncture using brain imaging techniques: the current state of play. Evid Based Complement Alternat Med. 2005;2:315–9. doi: 10.1093/ecam/neh110.
    1. Zhang WT, Jin Z, Cui GH, Zhang KL, Zhang L, Zeng YW, Luo F, Chen AC, Han JS. Relations between brain network activation and analgesic effect induced by low vs. high frequency electrical acupoint stimulation in different subjects: a functional magnetic resonance imaging study. Brain Res. 2003;982:168–78. doi: 10.1016/S0006-8993(03)02983-4.
    1. Dawidson I, Blom M, Lundeberg T, Angmar-Mansson B. The influence of acupuncture on salivary flow rates in healthy subjects. J Oral Rehabil. 1997;24:204–8. doi: 10.1111/j.1365-2842.1997.tb00314.x.
    1. Blom M, Lundeberg T. Long-term follow-up of patients treated with acupuncture for xerostomia and the influence of additional treatment. Oral Dis. 2000;6:15–24.
    1. Johnstone PA, Peng YP, May BC, Inouye WS, Niemtzow RC. Acupuncture for pilocarpine-resistant xerostomia following radiotherapy for head and neck malignancies. Int J Radiat Oncol Biol Phys. 2001;50:353–7. doi: 10.1016/S0360-3016(00)01530-3.
    1. Wong RK, Jones GW, Sagar SM, Babjak AF, Whelan T. A Phase I-II study in the use of acupuncture-like transcutaneous nerve stimulation in the treatment of radiation-induced xerostomia in head-and-neck cancer patients treated with radical radiotherapy. Int J Radiat Oncol Biol Phys. 2003;57:472–80. doi: 10.1016/S0360-3016(03)00572-8.
    1. Kahn ST, Johnstone PA. Management of xerostomia related to radiotherapy for head and neck cancer. Oncology (Williston Park) 2005;19:1827–32. discussion 32–4, 37–9.
    1. Johnstone PA, Polston GR, Niemtzow RC, Martin PJ. Integration of acupuncture into the oncology clinic. Palliat Med. 2002;16:235–9. doi: 10.1191/0269216302pm540oa.
    1. Johnstone PA, Niemtzow RC, Riffenburgh RH. Acupuncture for xerostomia: clinical update. Cancer. 2002;94:1151–6. doi: 10.1002/cncr.10348.
    1. Streitberger K, Kleinhenz J. Introducing a placebo needle into acupuncture research. Lancet. 1998;352:364–5. doi: 10.1016/S0140-6736(97)10471-8.
    1. de Weerth C, Graat G, Buitelaar JK, Thijssen JH. Measurement of cortisol in small quantities of saliva. Clin Chem. 2003;49:658–60. doi: 10.1373/49.4.658.
    1. Cox RW. AFNI: software for analysis and visualization of functional magnetic resonance neuroimages. Comput Biomed Res. 1996;29:162–73. doi: 10.1006/cbmr.1996.0014.
    1. Bandettini PA, Jesmanowicz A, Wong EC, Hyde JS. Processing strategies for time-course data sets in functional MRI of the human brain. Magn Reson Med. 1993;30:161–73. doi: 10.1002/mrm.1910300204.
    1. Cohen MS. Parametric analysis of fMRI data using linear systems methods. Neuroimage. 1997;6:93–103. doi: 10.1006/nimg.1997.0278.
    1. Logothetis NK, Pauls J, Augath M, Trinath T, Oeltermann A. Neurophysiological investigation of the basis of the fMRI signal. Nature. 2001;412:150–7. doi: 10.1038/35084005.
    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;34:1171–81. doi: 10.1016/j.neuroimage.2006.10.019.
    1. Kong J, Ma L, Gollub RL, Wei J, Yang X, Li D, Weng X, Jia F, Wang C, Li F, Li R, Zhuang D. 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;8:411–9. doi: 10.1089/107555302760253603.
    1. Tuor UI, Malisza K, Foniok T, Papadimitropoulos R, Jarmasz M, Somorjai R, Kozlowski P. Functional magnetic resonance imaging in rats subjected to intense electrical and noxious chemical stimulation of the forepaw. Pain. 2000;87:315–24. doi: 10.1016/S0304-3959(00)00293-1.
    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;9:463–84. doi: 10.1016/j.ejpain.2004.11.001.
    1. Wager TD, Rilling JK, Smith EE, Sokolik A, Casey KL, Davidson RJ, Kosslyn SM, Rose RM, Cohen JD. Placebo-induced changes in FMRI in the anticipation and experience of pain. Science. 2004;303:1162–7. doi: 10.1126/science.1093065.
    1. Hui KK, Liu J, Marina O, Napadow V, Haselgrove C, Kwong KK, Kennedy DN, Makris N. The integrated response of the human cerebro-cerebellar and limbic systems to acupuncture stimulation at ST 36 as evidenced by fMRI. Neuroimage. 2005;27:479–96. doi: 10.1016/j.neuroimage.2005.04.037.
    1. Ogawa H, Wakita M, Hasegawa K, Kobayakawa T, Sakai N, Hirai T, Yamashita Y, Saito S. Functional MRI detection of activation in the primary gustatory cortices in humans. Chem Senses. 2005;30:583–92. doi: 10.1093/chemse/bji052.
    1. Pritchard TC, Hamilton RB, Morse JR, Norgren R. Projections of thalamic gustatory and lingual areas in the monkey, Macaca fascicularis. J Comp Neurol. 1986;244:213–28. doi: 10.1002/cne.902440208.
    1. Cerf-Ducastel B, Moortele PF Van de, MacLeod P, Le Bihan D, Faurion A. Interaction of gustatory and lingual somatosensory perceptions at the cortical level in the human: a functional magnetic resonance imaging study. Chem Senses. 2001;26:371–83. doi: 10.1093/chemse/26.4.371.
    1. Morita M, Kurita A, Inoue K, Shimizu H, Mizutani T, Arai N. [A case with left mesial temporal lobe epilepsy characterized by abnormal massive salivation] Rinsho Shinkeigaku. 2001;41:809–12.
    1. Satow T, Ikeda A, Hayashi N, Yamamoto J, Takayama M, Matsuhashi M, Mikuni N, Takahashi J, Shibasaki H, Miyamoto S, Hashimoto N. Surgical treatment of seizures from the peri-Sylvian area by perinatal insult: a case report of ictal hypersalivation. Acta Neurochir (Wien) 2004;146:1021–5. doi: 10.1007/s00701-004-0311-7. discussion 6.

Source: PubMed

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