Carpal tunnel syndrome (CTS), the most common entrapment neuropathy, is exceeded only by low back pain as a cause of employee absenteeism. Maladaptive neuroplasticity in the brain of CTS patients has been noted by several neuroimaging studies, and includes altered primary somatosensory cortex (SI) somatotopy and SI hyperactivation, which may be due to cortical disinhibition. We hypothesize that the disability and pain associated with CTS is not only a consequence of the peripheral nerve lesion but also relates to the observed, altered cortical sensory processing. Acupuncture has shown potential as a conservative treatment option for CTS, but its mechanisms of action are unknown. CTS is an excellent model for studying acupuncture mechanisms as clinical improvement can be evaluated by several objective outcome measures in addition to subjective symptom assessments. We propose that acupuncture, a somatosensory conditioning stimulus, can reverse CTS-associated maladaptive neuroplasticity including cortical disinhibition via use-dependent plasticity. Furthermore, it is known that repetitive stimulation - in the healthy brain - results in temporally defined changes of cortical activity, the most prominent of which is a reduction in cortical response with extended stimulus duration. This is referred to as adaptation. Cortical disinhibition is known to modulate adaptation metrics. We propose that a biobehavioral assessment of cortical disinhibition quantified by maladaptive change in adaptation metrics will be sensitive to brain abnormalities in CTS. Thus, these metrics complement our fMRI data, potentially providing important cross-validation via an independent testing protocol. CTS patients randomized to verum acupuncture (forearm acupoints) and placebo acupuncture groups will be evaluated with adaptation metrics. We hypothesize that verum, but not sham acupuncture will alleviate CTS pathology and increase cortical inhibition, leading to normalization in adaptation metrics. Improvement in adaptation metrics will correlate with fMRI biomarkers and median nerve dysfunction. Hence, we will combine biobehavioral testing with fMRI neuroimaging to better delineate the central mechanisms by which acupuncture ameliorates CTS pathology. By understanding the neural mechanisms of different forms of acupuncture therapy, we hope to refine acupuncture utility for CTS and advance rehabilitation options in CTS care.

Public Health Relevance

Carpal tunnel syndrome (CTS) is a very common ailment resulting from excessive compression of the median nerve in the wrist and consistently leads in lost work time among major disabling injuries. Acupuncture has shown potential as a conservative treatment option for CTS, but its mechanisms of action are not known. This grant will assess changes in brain activity and cortical disinhibition that accompany the dysfunction in the wrist, as well as how acupuncture might modify both local nerve health and brain function to help treat CTS patients.

National Institute of Health (NIH)
National Center for Complementary & Alternative Medicine (NCCAM)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-MOSS-L (95))
Program Officer
Huntley, Kristen V
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Massachusetts General Hospital
United States
Zip Code
Long, Xiangyu; Huang, Wenjing; Napadow, Vitaly et al. (2016) Sustained Effects of Acupuncture Stimulation Investigated with Centrality Mapping Analysis. Front Hum Neurosci 10:510
Maeda, Yumi; Kettner, Norman; Kim, Jieun et al. (2016) Primary somatosensory/motor cortical thickness distinguishes paresthesia-dominant from pain-dominant carpal tunnel syndrome. Pain 157:1085-93
Desbordes, Gaƫlle; Li, Ang; Loggia, Marco L et al. (2015) Evoked itch perception is associated with changes in functional brain connectivity. Neuroimage Clin 7:213-21
Napadow, V; Li, A; Loggia, M L et al. (2015) The imagined itch: brain circuitry supporting nocebo-induced itch in atopic dermatitis patients. Allergy 70:1485-92
Loggia, Marco L; Berna, Chantal; Kim, Jieun et al. (2015) The lateral prefrontal cortex mediates the hyperalgesic effects of negative cognitions in chronic pain patients. J Pain 16:692-9
Loggia, Marco L; Edwards, Robert R; Harris, Richard E et al. (2014) Reply: To PMID 24449585. Arthritis Rheumatol 66:1684-5
Maeda, Yumi; Kettner, Norman; Holden, Jameson et al. (2014) Functional deficits in carpal tunnel syndrome reflect reorganization of primary somatosensory cortex. Brain 137:1741-52
Ichesco, Eric; Schmidt-Wilcke, Tobias; Bhavsar, Rupal et al. (2014) Altered resting state connectivity of the insular cortex in individuals with fibromyalgia. J Pain 15:815-826.e1
Napadow, Vitaly; Li, Ang; Loggia, Marco L et al. (2014) The brain circuitry mediating antipruritic effects of acupuncture. Cereb Cortex 24:873-82
Lee, Jeungchan; Napadow, Vitaly; Kim, Jieun et al. (2014) Phantom acupuncture: dissociating somatosensory and cognitive/affective components of acupuncture stimulation with a novel form of placebo acupuncture. PLoS One 9:e104582

Showing the most recent 10 out of 36 publications