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Traditional Chinese acupuncture and placebo (sham) acupuncture are differentiated by their effects on μ-opioid receptors (MORs)
Open accessAbstract
Controversy remains regarding the mechanisms of acupuncture analgesia. A prevailing theory, largely unproven in humans, is that it involves the activation of endogenous opioid antinociceptive systems and mu-opioid receptors (MORs). This is also a neurotransmitter system that mediates the effects of placebo-induced analgesia. This overlap in potential mechanisms may explain the lack of differentiation between traditional acupuncture and either non-traditional or sham acupuncture in multiple controlled clinical trials. We compared both short- and long-term effects of traditional Chinese acupuncture (TA) versus sham acupuncture (SA) treatment on in vivo MOR binding availability in chronic pain patients diagnosed with fibromyalgia (FM). Patients were randomized to receive either TA or SA treatment over the course of 4 weeks. Positron emission tomography (PET) with (11)C-carfentanil was performed once during the first treatment session and then repeated a month later following the eighth treatment. Acupuncture therapy evoked short-term increases in MOR binding potential, in multiple pain and sensory processing regions including the cingulate (dorsal and subgenual), insula, caudate, thalamus, and amygdala. Acupuncture therapy also evoked long-term increases in MOR binding potential in some of the same structures including the cingulate (dorsal and perigenual), caudate, and amygdala. These short- and long-term effects were absent in the sham group where small reductions were observed, an effect more consistent with previous placebo PET studies. Long-term increases in MOR BP following TA were also associated with greater reductions in clinical pain. These findings suggest that divergent MOR processes may mediate clinically relevant analgesic effects for acupuncture and sham acupuncture.
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“Pain relief produced by placebo,2,34,47,67,147 acupuncture,51 conditioned pain modulation,61 distraction,108 and hypnosis39,110 is meditated, in part, by endogenous opioidergic systems.”
From The neural mechanisms of mindfulness-based pain relief: a functional magnetic resonance imaging-based review and primer (2019) · cites this paper as [51]
In the citing paper
“Endogenous opioidergic mechanisms have been repeatedly demonstrated to mediate analgesia produced by placebo,89–93 conditioned pain modulation,94 acupuncture,95 hypnosis,96 and attentional control.97”
From Mindfulness meditation-based pain relief: a mechanistic account (2016) · cites this paper as [95]
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Metadata
- Authors
- Harris, R. E., Zubieta, J.-K., Scott, D. J., Napadow, V., Gracely, R. H., & Clauw, D. J.
- Affiliations
- University of Michigan (US)
- Omneuron (United States) (US)
- Massachusetts General Hospital (US)
- Corresponding author
- Harris, Richard E.
- Venue
- NeuroImage
- Publisher
- Elsevier BV
- Published
- 2009-09
- Volume
- 47
- Issue
- 3
- Pages
- 1077-1085
- ISSN
- 1053-8119 (ISSN-L)
- PMC
- PMC2757074
- OpenAlex
- W2156343006
- Cited by
- 296
- References
- 50
- Citations by year
- 2026: 9 · 2025: 9 · 2024: 11 · 2023: 17 · 2022: 22 · 2021: 16 · 2020: 14 · 2019: 24 · 2018: 8 · 2017: 18 · 2016: 15 · 2015: 14 · 2014: 17 · 2013: 26 · 2012: 31
- FWCI
- 61.06
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- NeuroImage (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (acceptedVersion)
- Funders
- National Center for Research Resources (M01RR000042)
- National Center for Complementary and Integrative Health (K01-AT-01111-01, R01AT001415, K01AT001111, K01AT002166, P01AT002048)
- Topics
- Health Sciences › Medicine › Complementary and alternative medicine › Acupuncture Treatment Research Studies
- Life Sciences › Neuroscience › Cognitive Neuroscience › Pain Management and Placebo Effect
- Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
- Keywords
- traditional Chinese acupuncture, sham acupuncture, mu-opioid receptor, opioid receptor binding, placebo analgesia, fibromyalgia, chronic pain, cingulate cortex, insula, amygdala, caudate nucleus, thalamus
- MeSH terms
- Adult, Brain, Brain Mapping, Chronic Disease, Female, Fibromyalgia, Humans, Image Interpretation, Computer-Assisted, Pain, Placebos, Acupuncture Analgesia, Placebo Effect, Receptors, Opioid, mu, Positron-Emission Tomography, Pain Management
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