While acupuncture has been shown to be effective for chronic low back pain (cLBP) in many clinical trials, there is a current state of uncertainty as to why acupuncture is effective. In multiple trials, acupuncture does not demonstrate significant improvement over placebo controls based on sham needling, which can involve insertive or non-insertive "needling" with a device that presses against the skin. However, the use of sham needling as placebo control has been criticized since it may be an active therapy akin to acupressure. Ultimately, this state of uncertainty arising from acupuncture clinical trials exists because we lack understanding about the mechanisms of action underlying real versus various forms of sham acupuncture. Specifically, we do not know just how important needle insertion and somatosensory afference are to the mechanisms underlying acupuncture analgesia in cLBP. There is reason to believe that real acupuncture may have different mechanisms from sham acupuncture, and we propose that neuroimaging can inform a testable neurobiological model that identifies diverse mechanisms of action for acupuncture therapy with versus without somatosensory afference. These hypotheses will be tested on a specific chronic pain population, idiopathic cLBP, which has a significant "central" pain component characterized by aberrant somatotopy and augmented brain response to experimental pain (hyperalgesia). The brain correlates of clinical pain in cLBP have been less well characterized, but our own data suggests that clinical pain is associated with increased intrinsic functional connectivity between pain processing brain regions (e.g insula) and specific intrinsic connectivity networks. These networks include the executive attention network (EAN) and "default mode network" (DMN), a network thought to underlie self-referential cognition and modulated by acupuncture. We propose that real and different forms of sham acupuncture differentially modulate these networks, and alter somatotopy. Our overall goal is to evaluate whether the brain neurocircuitry subserving cLBP responds differentially to real versus "sham" acupuncture with and without somatosensory afference. To test our specific hypotheses, we will employ functional magnetic resonance imaging (fMRI) to assess brain networks subserving both clinical and experimental pain, acupuncture stimulation, and somatotopy in cLBP patients. These measures will be performed at baseline and following 7 weeks of (a.) acupuncture, ACUP;(b.) sham acupuncture with somatosensation, SHAM-sn;(c.) sham acupuncture without somatosensation, SHAM-ml or (d.) wait list, WL.
Aim 1 will characterize the pain neurocircuitry in cLBP, as well as low back SI somatotopy, and brain response to acupuncture stimuli.
Aim 2 will evaluate longitudinal effects of ACUP vs. SHAM-sn on brain networks and SI somatotopy in cLBP, while Aim 3 will evaluate the longitudinal effects of SHAM-sn vs. SHAM-ml on these same neuroimaging markers. Understanding the neural influence of somatosensation on acupuncture placebo effects will significantly impact our understanding of acupuncture and allow for development of more inert acupuncture placebos.

Public Health Relevance

The morbidity and resultant financial costs associated with chronic low back pain (cLBP) are incredibly high. Unfortunately, conventional treatment options for cLBP have yielded only limited relief for patients. Acupuncture has been a popular option for treating cLBP but the mechanisms behind this therapy are not well understood. This proposal will differentiate the components of acupuncture for the treatment of cLBP using fMRI methodologies well suited for evaluating brain network plasticity in longitudinal studies.

Agency
National Institute of Health (NIH)
Type
Research Program Projects (P01)
Project #
5P01AT006663-04
Application #
8703017
Study Section
Special Emphasis Panel (ZAT1)
Project Start
Project End
Budget Start
Budget End
Support Year
4
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199
Rong, Peijing; Liu, Jun; Wang, Liping et al. (2016) Effect of transcutaneous auricular vagus nerve stimulation on major depressive disorder: A nonrandomized controlled pilot study. J Affect Disord 195:172-9
Fang, Jiliang; Rong, Peijing; Hong, Yang et al. (2016) Transcutaneous Vagus Nerve Stimulation Modulates Default Mode Network in Major Depressive Disorder. Biol Psychiatry 79:266-73
Long, Xiangyu; Huang, Wenjing; Napadow, Vitaly et al. (2016) Sustained Effects of Acupuncture Stimulation Investigated with Centrality Mapping Analysis. Front Hum Neurosci 10:510
Ellingsen, D-M; Garcia, R G; Lee, J et al. (2016) Cyclic Vomiting Syndrome is characterized by altered functional brain connectivity of the insular cortex: a cross-comparison with migraine and healthy adults. Neurogastroenterol Motil :
Wang, Xiaoyun; Wang, Zengjian; Liu, Jian et al. (2016) Repeated acupuncture treatments modulate amygdala resting state functional connectivity of depressive patients. Neuroimage Clin 12:746-752
Sclocco, Roberta; Kim, Jieun; Garcia, Ronald G et al. (2016) Brain Circuitry Supporting Multi-Organ Autonomic Outflow in Response to Nausea. Cereb Cortex 26:485-97
Tao, Jing; Liu, Jiao; Egorova, Natalia et al. (2016) Increased Hippocampus-Medial Prefrontal Cortex Resting-State Functional Connectivity and Memory Function after Tai Chi Chuan Practice in Elder Adults. Front Aging Neurosci 8:25
As-Sanie, Sawsan; Kim, Jieun; Schmidt-Wilcke, Tobias et al. (2016) Functional Connectivity is Associated With Altered Brain Chemistry in Women With Endometriosis-Associated Chronic Pelvic Pain. J Pain 17:1-13
Li, Zhengjie; Liu, Mailan; Lan, Lei et al. (2016) Altered periaqueductal gray resting state functional connectivity in migraine and the modulation effect of treatment. Sci Rep 6:20298
Hwang, J W; Xin, S C; Ou, Y M et al. (2016) Enhanced default mode network connectivity with ventral striatum in subthreshold depression individuals. J Psychiatr Res 76:111-20

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