Although acupuncture has been used to relieve pain for thousands of years, recent clinical trials investigating its efficacy on chronic pain have shown contradictory results. This ambiguity may derive from acupuncture's sizeable placebo effects, dosage imprecision as well as highly variable individual response to treatment. The mechanisms underlying these potential confounders remain unknown. In parallel, development in brain imaging provide scientists with new tools for investigating the neurobiological mechanisms underlying acupuncture treatment, and have advanced our understanding of the brain effects of acupuncture stimulation. However, most acupuncture neuroimaging studies to date have been conducted on healthy subjects using a single acupuncture needle in a single treatment session. This gap between the real clinical acupuncture practice and mechanistic research significantly hinders progress in the field and limits the implications of these research findings. In this proposal, we plan to dynamically investigate brain response to verum acupuncture (of two different """"""""doses"""""""") and placebo acupuncture, using a paradigm that approximates clinical acupuncture practice across multiple treatment sessions in knee osteoarthritis (OA) patients. This proposal aims to: 1) characterize session-to-session brain responses to verum / sham acupuncture treatment (reliability of response) for OA patients, and 2) investigate how different """"""""doses"""""""" of acupuncture influence brain response and acupuncture efficacy (impact of dose). Without such a clear mechanistic understanding of the variability in acupuncture response between different treatment sessions and the variability dependent on acupuncture """"""""dosage,"""""""" investigation of acupuncture's potential utility for clinical care will be severely limited. We have identified acupuncture treatment for OA as the most critical and urgent study population because acupuncture holds great promise for OA and there is a pressing need to clarify why well-designed acupuncture clinical trials have produced contradictory results. We believe this research takes a critical step forward in applying brain imaging tools to clinical studies of acupuncture. It will help deepen our biological understanding of acupuncture mechanisms and refine future clinical research protocols evaluating the therapy's potential benefits.

Public Health Relevance

Despite the fact that acupuncture has been used for more than 2000 years to relieve pain, scientific validation of the therapy and its underlying mechanisms remain poorly understood. This proposal will use a neuroimaging tool (fMRI) to investigate the brain response reliability and dose effect of acupuncture treatment on chronic pain patients. The findings of this project will deepen our biological understanding on why and how acupuncture can treat chronic pain and what happens in the brain during the multiple- session acupuncture treatment.

Agency
National Institute of Health (NIH)
Institute
National Center for Complementary & Alternative Medicine (NCCAM)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AT004497-01A2
Application #
7737968
Study Section
Special Emphasis Panel (ZAT1-LD (30))
Program Officer
Khalsa, Partap Singh
Project Start
2009-08-01
Project End
2011-04-30
Budget Start
2009-08-01
Budget End
2010-04-30
Support Year
1
Fiscal Year
2009
Total Cost
$375,207
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
Gollub, Randy L; Kirsch, Irving; Maleki, Nasim et al. (2018) A Functional Neuroimaging Study of Expectancy Effects on Pain Response in Patients With Knee Osteoarthritis. J Pain 19:515-527
Egorova, Natalia; Gollub, Randy L; Kong, Jian (2015) Repeated verum but not placebo acupuncture normalizes connectivity in brain regions dysregulated in chronic pain. Neuroimage Clin 9:430-5
Chen, Xiaoyan; Spaeth, Rosa B; Freeman, Sonya G et al. (2015) The modulation effect of longitudinal acupuncture on resting state functional connectivity in knee osteoarthritis patients. Mol Pain 11:67
Jensen, Karin B; Kaptchuk, Ted J; Chen, Xiaoyan et al. (2015) A Neural Mechanism for Nonconscious Activation of Conditioned Placebo and Nocebo Responses. Cereb Cortex 25:3903-10
Chen, Xiaoyan; Spaeth, Rosa B; Retzepi, Kallirroi et al. (2014) Acupuncture modulates cortical thickness and functional connectivity in knee osteoarthritis patients. Sci Rep 4:6482
Jensen, K B; Petrovic, P; Kerr, C E et al. (2014) Sharing pain and relief: neural correlates of physicians during treatment of patients. Mol Psychiatry 19:392-8
Yu, Rongjun; Gollub, Randy L; Spaeth, Rosa et al. (2014) Disrupted functional connectivity of the periaqueductal gray in chronic low back pain. Neuroimage Clin 6:100-8
Yu, Rongjun; Gollub, Randy L; Vangel, Mark et al. (2014) Placebo analgesia and reward processing: integrating genetics, personality, and intrinsic brain activity. Hum Brain Mapp 35:4583-93
Kong, Jian; Jensen, Karin; Loiotile, Rita et al. (2013) Functional connectivity of the frontoparietal network predicts cognitive modulation of pain. Pain 154:459-67
Spaeth, Rosa B; Camhi, Stephanie; Hashmi, Javeria A et al. (2013) A longitudinal study of the reliability of acupuncture deqi sensations in knee osteoarthritis. Evid Based Complement Alternat Med 2013:204259

Showing the most recent 10 out of 26 publications