Dataset Information

Enhancing treatment of osteoarthritis knee pain by boosting expectancy: A functional neuroimaging study.

ABSTRACT:

Objectives

Expectation can significantly modulate pain and treatment effects. This study aims to investigate if boosting patients' expectancy can enhance the treatment of knee osteoarthritis (KOA), and its underlying brain mechanism.

Methods

Seventy-four KOA patients were recruited and randomized to three groups: boosted acupuncture (with a manipulation to enhance expectation), standard acupuncture, or treatment as usual (TAU). Each patient underwent six treatments before being debriefed, and four additional treatments after being debriefed. The fMRI scans were applied during the first and sixth treatment sessions.

Results

We found significantly decreased knee pain in the boosted acupuncture group compared to the standard acupuncture or TAU groups after both six and ten treatments. Resting state functional connectivity (rsFC) analyses using the nucleus accumbens (NAc) as the seed showed rsFC increases between the NAc and the medial prefrontal cortex (MPFC)/rostral anterior cingulate cortex (rACC) and dorsolateral prefrontal cortex in the boosted group as compared to the standard acupuncture group after multiple treatments. Expectancy scores after the first treatment were significantly associated with increased NAc-rACC/MPFC rsFC and decreased knee pain following treatment.

Conclusions

Our study provides a novel method and mechanism for boosting the treatment of pain in patients with KOA. Our findings may shed light on enhancing outcomes of pharmacological and integrative medicines in clinical settings.

SUBMITTER: Kong J

PROVIDER: S-EPMC5984593 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Enhancing treatment of osteoarthritis knee pain by boosting expectancy: A functional neuroimaging study.

Kong Jian J Wang Zengjian Z Leiser Jaclyn J Minicucci Domenic D Edwards Robert R Kirsch Irving I Wasan Ajay D AD Lang Courtney C Gerber Jessica J Yu Siyi S Napadow Vitaly V Kaptchuk Ted J TJ Gollub Randy L RL

NeuroImage. Clinical 20180228

<h4>Objectives</h4>Expectation can significantly modulate pain and treatment effects. This study aims to investigate if boosting patients' expectancy can enhance the treatment of knee osteoarthritis (KOA), and its underlying brain mechanism.<h4>Methods</h4>Seventy-four KOA patients were recruited and randomized to three groups: boosted acupuncture (with a manipulation to enhance expectation), standard acupuncture, or treatment as usual (TAU). Each patient underwent six treatments before being de ...[more]

PMID: 29868449

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Project description:Placebo treatments and healing rituals share much in common, such as the effects of expectancy, and have been used since the beginning of human history to treat pain. Previous mechanistic neuroimaging studies investigating the effects of expectancy on placebo analgesia have used young, healthy volunteers. Using functional magnetic resonance imaging (fMRI), we aimed to investigate the neural mechanisms by which expectancy evokes analgesia in older adults living with a chronic pain disorder and determine whether there are interactions with active treatment. In this fMRI study, we investigated the brain networks underlying expectancy in participants with chronic pain due to knee osteoarthritis (OA) after verum (genuine) and sham electroacupuncture treatment before and after experiencing calibrated experimental heat pain using a well tested expectancy manipulation model. We found that expectancy significantly and similarly modulates the pain experience in knee OA patients in both verum (n?=?21, 11 female; mean?±?SD age 57?±?7 years) and sham (n?=?22, 15 female; mean?±?SD age 59?±?7 years) acupuncture treatment groups. However, there were different patterns of changes in fMRI indices of brain activity associated with verum and sham treatment modalities specifically in the lateral prefrontal cortex. We also found that continuous electroacupuncture in knee OA patients can evoke significant regional coherence decreases in pain associated brain regions. Our results suggest that expectancy modulates the experience of pain in knee OA patients but may work through different pathways depending on the treatment modality and, we speculate, on pathophysiological states of the participants. PERSPECTIVE:To investigate the neural mechanisms underlying pain modulation, we used an expectancy manipulation model and fMRI to study response to heat pain stimuli before and after verum or sham acupuncture treatment in chronic pain patients. Both relieve pain and each is each associated with a distinct pattern of brain activation.

Project description:BackgroundIncreased expression of nerve growth factor in injured or inflamed tissue is associated with increased pain. This proof-of-concept study was designed to investigate the safety and analgesic efficacy of tanezumab, a humanized monoclonal antibody that binds and inhibits nerve growth factor.MethodsWe randomly assigned 450 patients with osteoarthritis of the knee to receive tanezumab (administered at a dose of 10, 25, 50, 100, or 200 μg per kilogram of body weight) or placebo on days 1 and 56. The primary efficacy measures were knee pain while walking and the patient's global assessment of response to therapy. We also assessed pain, stiffness, and physical function using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC); the rate of response using the criteria of the Outcome Measures for Rheumatology Committee and Osteoarthritis Research Society International Standing Committee for Clinical Trials Response Criteria Initiative (OMERACT-OARSI); and safety.ResultsWhen averaged over weeks 1 through 16, the mean reductions from baseline in knee pain while walking ranged from 45 to 62% with various doses of tanezumab, as compared with 22% with placebo (P<0.001). Tanezumab, as compared with placebo, was also associated with significantly greater improvements in the response to therapy as assessed with the use of the patients' global assessment measure (mean increases in score of 29 to 47% with various doses of tanezumab, as compared with 19% with placebo; P≤0.001). The rate of response according to the OMERACT-OARSI criteria ranged from 74 to 93% with tanezumab treatment, as compared with 44% with placebo (P<0.001). The rates of adverse events were 68% and 55% in the tanezumab and placebo groups, respectively. The most common adverse events among tanezumab-treated patients were headache (9% of the patients), upper respiratory tract infection (7%), and paresthesia (7%).ConclusionsIn this proof-of-concept study, treatment with tanezumab was associated with a reduction in joint pain and improvement in function, with mild and moderate adverse events, among patients with moderate-to-severe osteoarthritis of the knee. (Funded by Rinat Neuroscience; ClinicalTrials.gov number, NCT00394563.).

Project description:IntroductionKnee osteoarthritis is a common disease in the elderly. Patients suffer from long-term chronic pain and reduced life quality. Acupuncture has been proven to be an effective treatment for KOA. However, the neural mechanism of acupuncture is unclear, so far. Periaqueductal gray (PAG) and raphe nuclei (RPN) are essential structures associated with chronic pain in human brains. This study aims to investigate functional connectivity (FC) changes of PAG and RPN in KOA to interpret the neural mechanism of acupuncture.MethodsIn 15 patients with KOA and 15 healthy controls (HC), we acquired Visual Analog Scale (VAS) scores and resting-state fMRI images of each participant before and after acupuncture stimulation on EX-LE5 acupoint. Then, PAG and RPN were selected as seeds to perform FC analysis based on resting-state fMRI images. Finally, we compared FC patterns of PAG and RPN between patients with KOA and HC, then between pre-acupuncture and post-acupuncture. Correlations between FC values and VAS scores were calculated as well.ResultsFor PAG, FC of patients with KOA was lower in the right lingual gyrus at post-acupuncture compared with HC (p <0.001, uncorrected). For dorsal RPN, FC of patients with KOA was significantly higher in right putamen at post-acupuncture compared with HC (p <0.001, corrected with FDR), and FC changes were significant between pre-acupuncture and post-acupuncture in patients with KOA. Post-acupuncture FC values between dorsal RPN and right putamen were correlated with VAS scores. For medial RPN, FC of patients with KOA was lower in the right cerebellum at post-acupuncture compared with HC (p <0.001, uncorrected), but no significant FC changes were found between pre-acupuncture and post-acupuncture in patients with KOA. FC values between medial RPN and right cerebellum were not correlated with VAS scores at pre-acupuncture and post-acupuncture.DiscussionOur study demonstrated that acupuncture enhanced FC between dorsal RPN and the right putamen in patients with KOA, which was associated with chronic pain intensity. This result suggests that acupuncture stimulation can enhance FC between dorsal raphe and striatum, illustrating a neural mechanism that acupuncture can drive the patients' brain, with KOA, to perceive pain.

Dataset Information

Enhancing treatment of osteoarthritis knee pain by boosting expectancy: A functional neuroimaging study.

Objectives

Methods

Results

Conclusions

Publications

Enhancing treatment of osteoarthritis knee pain by boosting expectancy: A functional neuroimaging study.

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