Mol Pain
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Randomized Controlled Trial Clinical Trial
The modulation effect of longitudinal acupuncture on resting state functional connectivity in knee osteoarthritis patients.
Recent advances in brain imaging have contributed to our understanding of the neural activity associated with acupuncture treatment. In this study, we investigated functional connectivity across longitudinal acupuncture treatments in older patients with knee osteoarthritis (OA). Over a period of 4 weeks (six treatments), we collected resting state functional magnetic resonance imaging (fMRI) scans from 30 patients before and after their first, third and sixth treatments. Clinical outcome showed a significantly greater pain subscore on the Knee Injury and Osteoarthritis Outcome Score (KOOS) (indicative of improvement) with verum acupuncture than with sham acupuncture. Independent component analysis (ICA) of the resting state fMRI data showed that the right frontoparietal network (rFPN) and the executive control network (ECN) showed enhanced functional connectivity (FC) with the rostral anterior cingulate cortex/medial prefrontal cortex, a key region in the descending pain modulatory system, in the verum groups as compared to the sham group after treatments. We also found that the rFPN connectivity with the left insula is (1) significantly associated with changes in KOOS pain score after treatments, and (2) significantly enhanced after verum acupuncture treatments as compared to sham treatment. Analysis of the acupuncture needle stimulation scan showed that compared with sham treatment, verum acupuncture activated the left operculum/insula, which also overlaps with findings observed in resting state analysis. Our results suggest that acupuncture may achieve its therapeutic effect on knee OA pain by modulating functional connectivity between the rFPN, ECN and the descending pain modulatory pathway. ⋯ NCT01079390.
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Randomized Controlled Trial
A simplified up-down method (SUDO) for measuring mechanical nociception in rodents using von Frey filaments.
The measurement of mechanosensitivity is a key method for the study of pain in animal models. This is often accomplished with the use of von Frey filaments in an up-down testing paradigm. The up-down method described by Chaplan et al. (J Neurosci Methods 53:55-63, 1994) for mechanosensitivity testing in rodents remains one of the most widely used methods for measuring pain in animals. However, this method results in animals receiving a varying number of stimuli, which may lead to animals in different groups receiving different testing experiences that influences their later responses. To standardize the measurement of mechanosensitivity we developed a simplified up-down method (SUDO) for estimating paw withdrawal threshold (PWT) with von Frey filaments that uses a constant number of five stimuli per test. We further refined the PWT calculation to allow the estimation of PWT directly from the behavioral response to the fifth stimulus, omitting the need for look-up tables. ⋯ SUDO thus offers an accurate, fast and user-friendly replacement for the widely used up-down method of Chaplan et al.
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Randomized Controlled Trial
Lidocaine patch (5%) is no more potent than placebo in treating chronic back pain when tested in a randomised double blind placebo controlled brain imaging study.
The 5% Lidocaine patch is used for treating chronic neuropathic pain conditions such as chronic back pain (CBP), diabetic neuropathy and complex regional pain syndrome, but is effective in a variable proportion of patients. Our lab has reported that this treatment reduces CBP intensity and associated brain activations when tested in an open labelled preliminary study. Notably, effectiveness of the 5% Lidocaine patch has not been tested against placebo for treating CBP. In this study, effectiveness of the 5% Lidocaine patch was compared with placebo in 30 CBP patients in a randomised double-blind study where 15 patients received 5% Lidocaine patches and the remaining patients received placebo patches. Functional MRI was used to identify brain activity for fluctuations of spontaneous pain, at baseline and at two time points after start of treatment (6 hours and 2 weeks). ⋯ These findings suggest that although the 5% Lidocaine is not better than placebo in its effectiveness for treating pain, the patch itself induces a potent placebo effect in a significant proportion of CBP patients.
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Randomized Controlled Trial
Imaging the functional connectivity of the Periaqueductal Gray during genuine and sham electroacupuncture treatment.
Electroacupuncture (EA) is currently one of the most popular acupuncture modalities. However, the continuous stimulation characteristic of EA treatment presents challenges to the use of conventional functional Magnetic Resonance Imaging (fMRI) approaches for the investigation of neural mechanisms mediating treatment response because of the requirement for brief and intermittent stimuli in event related or block designed task paradigms. A relatively new analysis method, functional connectivity fMRI (fcMRI), has great potential for studying continuous treatment modalities such as EA. In a previous study, we found that, compared with sham acupuncture, EA can significantly reduce Periaqueductal Gray (PAG) activity when subsequently evoked by experimental pain. Given the PAG's important role in mediating acupuncture analgesia, in this study we investigated functional connectivity with the area of the PAG we previously identified and how that connectivity was affected by genuine and sham EA. ⋯ Our findings indicate the intrinsic functional connectivity changes among key brain regions in the pain matrix and default mode network during genuine EA compared with sham EA. We speculate that continuous genuine EA stimulation can modify the coupling of spontaneous activity in brain regions that play a role in modulating pain perception.