Research Review By Dr. Ceara Higgins©


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Date Posted:

May 2016

Study Title:

Does Acupuncture Alter Pain-Related Functional Connectivity of the Central Nervous System? A Systematic Review


Villarreal Santiago M, Tumilty S, Macznik A, Mani R

Author's Affiliations:

Centre for Health, Activity and Rehabilitation Research, School of Physiotherapy, University of Otago, Dunedin, New Zealand.

Publication Information:

Journal of Acupuncture and Meridian Studies 2016; 9(4): 167-77.

Background Information:

Acupuncture has long been used to treat pain-related disorders. The current evidence attributes the effects of acupuncture to physiological mechanisms such as peripheral, central, and neurohormonal responses (1). Since their development, neuroimaging techniques such as functional magnetic resonance imaging (fMRI), positron emission tomography (PET), single photon emission computed tomography (SPECT), electroencephalography, and magnetoencephalography have allowed us to examine the effects of acupuncture treatment on the functional connectivity of the brain (2).

Notable differences in brain activity are often seen when comparing acute to chronic pain populations. Chronic pain patients typically show high levels of abnormal functional neuroplastic change in regional brain connectivity, which is correlated with pain intensity (6). Interestingly, these areas of abnormal activity associated with chronic pain are different than areas of brain activation visualized in acute pain states (5).

Current evidence defines the following cortical and subcortical areas as the “pain matrix” (4):
  1. Primary somatosensory cortex (S1)
  2. Secondary somatosensory cortex (S2)
  3. Insular cortex (IC)
  4. Anterior cingulate cortex (ACC)
  5. Amygdala
  6. Prefrontal cortex (PFC)
  7. Thalamus
Acupuncture studies using neuroimaging have shown brain activation in the IC, thalamus, ACC, S1, S2, inferior frontal cortex, superior temporal cortex, superior temoporal gyrus, and cerebellum; and deactivation in the medial prefrontal cortex, subgenual ACC, caudate, hippocampus, and cerebellum (8) with acupuncture treatments. However, most of these studies were performed on healthy individuals (2), which calls into question the validity of these findings in pain patients. Therefore, the aim of this systematic review was to evaluate existing evidence for the effectiveness of acupuncture in influencing the functional connectivity of the central nervous system in patients with musculoskeletal pain.

Pertinent Results:

Included Studies:
Seven studies were included in this review. Of these, three were RCTs (9-11) and four were non-RCTs (12-15). The studies involved a total of 191 participants, of which 83% were between 31-60 years of age. The clinical conditions represented among these studies included osteoarthritis (9, 15), chronic low back pain (12), carpal tunnel syndrome (10, 13, 14), and fibromyalgia (11) with a minimum pain duration of 3 months in five studies, 1 year in 1 study, and no duration reported in 1 study.

Summary of Included Studies:
Acupuncture was utilized in four studies (9, 11, 12, 15), electroacupuncture in one (10), and a combination of acupuncture and electroacupuncture in the remaining two (13, 14). Intervention periods ranged from four to five weeks, with 6-13 sessions in five studies (9, 11-14) while the remaining two studies utilized a single session (10, 15). Comparison interventions included sham acupuncture or electroacupuncture (9-11, 15) or healthy participants receiving no acupuncture (12-14). In five studies, fMRI was used (9, 10, 12-14) and in two PET scanning was utilized (11,15). Two studies performed the neuroimaging during treatment (10, 15), while the other five either performed neuroimaging before or after treatment with a variety of timeframes and number of sessions (9, 11-14). When assessed using a modified Downs and Black questionnaire, six studies were rated of high methodological quality and one of moderate quality.

Five studies assessed the effect of acupuncture on pain, with four of these studies reporting a significant reduction in pain post-intervention. All of these studies showed brain activation in the PFC (85% of cases), ACC (71%), and IC (57%), regardless of the length of the acupuncture intervention. Brain activation was also commonly visualized in areas associated with the pain matrix, namely the amygdala, S1, S2, and thalamus (3).

Previous studies have also proven the existence of abnormal connectivity in both cortical and subcortical regions of the brain in chronic pain patients (7). The five studies which focused on chronic pain all showed that long-term acupuncture interventions showed positive functional changes or alterations in connectivity in the above brain areas, resulting in a reversal of abnormal plasticity (9, 11-14). In three of these studies, restoring normal plasticity was positively correlated with a clinical reduction in pain (9, 11, 12).

In the four studies that investigated the short-term response to acupuncture, activation of the pain matrix was seen (10, 11, 14, 15). However, no conclusions can be drawn with regards to abnormal plasticity and only one study showed positive correlations with clinical pain (10). Sham acupuncture was shown to have no significant effect on pain and no restoration of abnormal connectivity was noted.

Clinical Application & Conclusions:

Acupuncture has been proven to cause important changes in chronic pain states and is most effective in these patients when used as a long-term intervention. More specifically, functional connectivity changes have been noted among patients with chronic pain and this restoration of normal functional connectivity has been correlated with pain reduction. Thus, acupuncture can be utilized as an effective intervention in patients with chronic pain.

Study Methods:

The authors searched and extracted relevant studies from multiple databases. Two independent reviewers first screened articles by title, next by abstract, and finally by full-text using the inclusion/exclusion criteria outlined below. Any disagreements about study inclusion were resolved through discussion. A third reviewer was consulted if consensus was not reached.

Inclusion Criteria:
  • Randomized Controlled Trials (RCTs) and nonrandomized studies
  • Published in peer-reviewed journals
  • Participants with acute or chronic musculoskeletal pain
  • Studies using acupuncture or electroacupuncture
  • Studies using sham acupuncture or no intervention as a control
  • Studies using fMRI, PET, SPECT, electroencephalography, or magnetoencephalography to assess functional connectivity
Exclusion Criteria:
  • Non-English language publications
  • Studies using ear acupuncture, moxibustion, acupressure, laser acupuncture, or dry needling
Data was extracted from the selected studies by one reviewer and checked for accuracy by a second reviewer. Extracted data included:
  • Study design
  • Study participants’ demographics
  • Details of intervention
  • Brain imaging technique and assessment time frame
  • Results
The data was then categorized into long-term (multiple sessions of acupuncture) and short-term (one session of acupuncture) intervention periods under the following categories:
  • Brain imaging techniques
  • Diagnosis
  • Activated/deactivated brain areas
  • Reported reduction in pain

Study Strengths / Weaknesses:

  • The review was conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines
  • Search strategies were developed with the guidance of a university librarian.
  • It was difficult to compare the study outcomes due to logistical reasons, such as brain deactivation/activation variability, lack of information regarding neuroimaging data reports, and reporting styles.
  • Studies commonly lacked information on depth of needle insertion, needle retention time, and needle type.
  • This review included a limited number of studies.
  • No description of the pain matrix was included. As the activation of areas of the brain overlying this area was noted as important, it would be helpful to have a description of what this is in order to contextualize the importance of the activation of overlying areas.
  • There was no discussion of the importance, or lack thereof, of needling traditional acupuncture points in order to elicit the noted responses.

Additional References:

  1. Zhao ZQ. Neural mechanism underlying acupuncture analgesia. Prog Neurobiol 2008; 85: 355-375.
  2. Dhond RP, Kettner N, Napadow V. Neuoimaging acupuncture effects in the human brain. J Altern Complem Med 2007; 13: 603-616.
  3. Apkarian AV, Bushnell MC, Treede RD, et al. Human brain mechanisms of pain perception and regulation in health and disease. Eur J Pain 2005; 9: 463-484.
  4. Iannetti GD, Mouraux A. From the neuromatrix to the pain matrix (and back). Exp Brain Res 2010; 205: 1-12.
  5. May A. Neuroimaging: visualising the brain in pain. Neurol Sci 2007; 28(Suppl 2): S101-S107.
  6. Farmer MA, Baliki MN, Apkarian AV. A dynamic network perspective of chronic pain. Neurosci Lett 2012; 520: 197-203.
  7. Henry DE, Chiodo AE, Yang W. Central nervous system reorganization in a variety of chronic pain states: a review. PM R 2011; 3: 1116-1125.
  8. Chae Y, Chang DS, Lee SH, et al. Inserting needles into the body: a meta-analysis of brain activity associated with acupuncture needle stimulation. J Pain 2013; 14: 215-222.
  9. Chen X, Spaeth RB, Retzepi, et al. Acupuncture modulates cortical thickness and functional connectivity in knee osteoarthritis patients. Sci Rep 2014; 4: 6482.
  10. Maeda Y, Kettner N, Lee J, et al. Acupuncture-evoked response in somatosensory and prefrontal cortices predicts immediate pain reduction in carpal tunnel syndrome. Evid Based Complement Alternat Med 2013; 2013: 1-13.
  11. Harris RE, Zubieta JK, Scott DJ, et al. Traditional Chinese acupuncture and placebo (sham) acupuncture are differentiated by their effects on mu-opiod receptors (MORs). Neuroimage 2009; 47: 1077-1085.
  12. Li J, Zhang JH, Yi T, et al. Acupuncture treatment of chronic low back pain reverses an abnormal brain default mode network in correlation with clinical pain relief. Acupunct Med 2014; 32: 102-108.
  13. Napadow V, Liu J, Li M, et al. Somatosensory cortical plasticity in carpal tunnel syndrome treated by acupuncture. Hum Brain Mapp 2007; 28: 159-171.
  14. Napadow V, Kettner N, Liu J, et al. Hypothalamus and amygdala response to acupuncture stimuli in carpal tunnel syndrome. Pain 2007; 130: 254-266.
  15. Pariente J, White P, Frackowiak RS, et al. Expectancy and belief modulate the neuronal substrates of pain treated by acupuncture. Neuroimage 2005; 25: 1161-1167.