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Edwards, Robert

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Edwards

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Edwards, Robert
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    The modulation effect of longitudinal acupuncture on resting state functional connectivity in knee osteoarthritis patients
    (BioMed Central, 2015) Chen, Xiaoyan; Spaeth, Rosa B.; Freeman, Sonya G.; Scarborough, Donna Moxley; Hashmi, Javeria A.; Wey, Hsiao-Ying; Egorova, Natalia; Vangel, Mark; Mao, Jianren; Wasan, Ajay D.; Edwards, Robert; Gollub, Randy; Kong, Jian
    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. Clinical trial number: NCT01079390 Electronic supplementary material The online version of this article (doi:10.1186/s12990-015-0071-9) contains supplementary material, which is available to authorized users.
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    Influence of opioid-related side effects on disability, mood, and opioid misuse risk among patients with chronic pain in primary care
    (Wolters Kluwer, 2017) Jamison, Robert; Dorado, Kathleen; Mei, Anna; Edwards, Robert; Martel, Marc O.
    Abstract Background: There is increasing concern among primary care practitioners about the use of opioids for chronic pain, including their adverse effects, but little attention has been given to how reports of side effects from prescription medication can contribute to outcomes among patients with chronic pain. The aim of this study was to investigate the impact of frequently reported side effects on mood, disability, and opioid misuse in patients with chronic pain prescribed opioids within primary care. Methods: Two hundred (N = 200) patients with chronic pain taking opioids for pain were recruited into the study. All patients completed baseline measures and a monthly side effects checklist once a month for 6 months. Patients were divided evenly based on a median split of the number of endorsed side effects over 6 months. The subjects repeated the baseline measures at the end of the study period. Results: Over time, reports of medication side effects tended to decrease, but differences in frequency of reported side effects from baseline to follow-up (6-month time) were not significant, and the order of the frequency of the reported side effects remained similar. Patients who reported significant medication-related adverse effects reported significantly greater activity interference, negative affect, and catastrophizing compared with those with fewer side effects (P < 0.01). In addition, those patients with pain who reported more side effects showed significantly higher scores on opioid misuse risk (P < 0.001). Discussion: This study demonstrates the important role of monitoring medication-related side effects among patients with chronic pain who are prescribed opioid medication for pain within primary care.
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    Neuropathic pain drives anxiety behavior in mice, results consistent with anxiety levels in diabetic neuropathy patients
    (Wolters Kluwer, 2018) Sieberg, Christine B.; Taras, Caitlin; Gomaa, Aya; Nickerson, Chelsea; Wong, Cindy; Ward, Catherine; Baskozos, Georgios; Bennett, David L.H.; Ramirez, Juan D.; Themistocleous, Andreas C.; Rice, Andrew S.C.; Shillo, Pallai R.; Tesfaye, Solomon; Edwards, Robert; Andrews, Nick A.; Berde, Charles; Costigan, Michael
    Abstract Background: Epidemiological studies in patients with neuropathic pain demonstrate a strong association with psychiatric conditions such as anxiety; however, the precipitating pathology between these symptoms remains unclear. To investigate this, we studied the effects of lifelong stress on levels of neuropathic pain–like behavior and conversely, the effects of chronic neuropathic injury on anxiety-like status in male and female mice. In addition, we assayed this link in painful and painless diabetic peripheral neuropathy patients. Methods: Male and female mice were subject to ongoing life-stress or control living conditions. Baseline sensitivity and anxiety tests were measured followed by spared nerve injury (SNI) to the sciatic nerve. Subsequent sensory testing occurred until 3 weeks after SNI followed by anxiety tests between 4 and 6 weeks after SNI. Results: Levels of tactile or cold allodynia did not differ between adult mice subject to lifelong chronic stress, relative to nonstressed controls, for at least 3 weeks after SNI. By contrast, longer-term neuropathic mice of both sexes displayed pronounced anxiety-like behavior, regardless of exposure to stress. If sex differences were present, females usually exhibited more pronounced anxiety-like behavior. These ongoing anxiety behaviors were corroborated with plasma corticosterone levels in distinct animal groups. In addition, data from patients with painful and nonpainful diabetic neuropathy showed a clear relationship between ongoing pain and anxiety, with females generally more affected than males. Discussion: Taken together, these data demonstrate a strong link between chronic neuropathic pain and chronic anxiety, with the driver of this comorbidity being neuropathic pain as opposed to on-going stress.
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    Enhancing treatment of osteoarthritis knee pain by boosting expectancy: A functional neuroimaging study
    (Elsevier, 2018) Kong, Jian; Wang, Zengjian; Leiser, Jaclyn; Minicucci, Domenic; Edwards, Robert; Kirsch, Irving; Wasan, Ajay D.; Lang, Courtney; Gerber, Jessica; Yu, Siyi; Napadow, Vitaly; Kaptchuk, Ted; Gollub, Randy
    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.
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    Androgen Deprivation Therapy Is Associated With Prolongation of QTc Interval in Men With Prostate Cancer
    (Endocrine Society, 2018) Gagliano-Jucá, Thiago; Travison, Thomas G; Kantoff, Philip W; Nguyen, Paul L; Taplin, Mary-Ellen; Kibel, Adam; Huang, Grace; Bearup, Richelle; Schram, Haley; Manley, Robert; Beleva, Yusnie M; Edwards, Robert; Basaria, Shehzad
    Abstract Context Androgen deprivation therapy (ADT) for prostate cancer (PCa) is associated with increased cardiovascular mortality and sudden cardiac death, with some events occurring early after initiation of ADT. Testosterone levels are inversely associated with corrected QT (QTc) interval duration; therefore, prolongation of QTc duration could be responsible for some of these events during ADT. Objective: To evaluate changes in QTc duration during ADT. Design and Interventions A 6-month prospective cohort study that enrolled men with PCa about to undergo ADT (ADT group) and a control group of men who previously underwent prostatectomy for PCa and never received ADT (non-ADT group). Patients At study entry, all participants were eugonadal and had no history of cardiac arrhythmias or complete bundle branch block. Outcomes Difference in change in QTc duration from baseline on a 12-lead electrocardiogram at 6, 12, and 24 weeks after initiation of ADT compared with electrocardiograms performed at the same intervals in the non-ADT group. PR, QRS, and QT interval durations were also evaluated. Results: Seventy-one participants formed the analytical sample (33 ADT and 38 non-ADT). ADT was associated with prolongation of the QTc by 7.4 ms compared with the non-ADT group [95% confidence interval (CI) 0.08 to 14.7 ms; P = 0.048]. ADT was also associated with shortening of the QRS interval by 2.4 ms (95% CI −4.64 to −0.23; P = 0.031). Electrolytes did not change. Conclusions: Men undergoing ADT for PCa experienced prolongation of the QTc. These findings might explain the increased risk of sudden cardiac death seen in these patients.
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    A Longitudinal Study of the Reliability of Acupuncture Deqi Sensations in Knee Osteoarthritis
    (Hindawi Publishing Corporation, 2013) Spaeth, Rosa B.; Camhi, Stephanie; Hashmi, Javeria A.; Vangel, Mark; Wasan, Ajay D.; Edwards, Robert; Gollub, Randy; Kong, Jian
    Deqi is one of the core concepts in acupuncture theory and encompasses a range of sensations. In this study, we used the MGH Acupuncture Sensation Scale (MASS) to measure and assess the reliability of the sensations evoked by acupuncture needle stimulation in a longitudinal clinical trial on knee osteoarthritis (OA) patients. The Knee injury and Osteoarthritis Outcome Score (KOOS) was used as the clinical outcome. Thirty OA patients were randomized into one of three groups (high dose, low dose, and sham acupuncture) for 4 weeks. We found that, compared with sham acupuncture, real acupuncture (combining high and low doses) produced significant improvement in knee pain (P = .025) and function in sport (P = .049). Intraclass correlation analysis showed that patients reliably rated 11 of the 12 acupuncture sensations listed on the MASS and that heaviness was rated most consistently. Overall perceived sensation (MASS Index) (P = .014), ratings of soreness (P = .002), and aching (P = .002) differed significantly across acupuncture groups. Compared to sham acupuncture, real acupuncture reliably evoked stronger deqi sensations and led to better clinical outcomes when measured in a chronic pain population. Our findings highlight the MASS as a useful tool for measuring deqi in acupuncture research.
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    Dissociable Neural Mechanisms Underlying the Modulation of Pain and Anxiety? An fMRI Pilot Study
    (Public Library of Science, 2014) Wiech, Katja; Edwards, Robert; Moseley, Graham Lorimer; Berna, Chantal; Ploner, Markus; Tracey, Irene
    The down-regulation of pain through beliefs is commonly discussed as a form of emotion regulation. In line with this interpretation, the analgesic effect has been shown to co-occur with reduced anxiety and increased activity in the ventrolateral prefrontal cortex (VLPFC), which is a key region of emotion regulation. This link between pain and anxiety modulation raises the question whether the two effects are rooted in the same neural mechanism. In this pilot fMRI study, we compared the neural basis of the analgesic and anxiolytic effect of two types of threat modulation: a “behavioral control” paradigm, which involves the ability to terminate a noxious stimulus, and a “safety signaling” paradigm, which involves visual cues that signal the threat (or absence of threat) that a subsequent noxious stimulus might be of unusually high intensity. Analgesia was paralleled by VLPFC activity during behavioral control. Safety signaling engaged elements of the descending pain control system, including the rostral anterior cingulate cortex that showed increased functional connectivity with the periaqueductal gray and VLPFC. Anxiety reduction, in contrast, scaled with dorsolateral prefrontal cortex activation during behavioral control but had no distinct neural signature during safety signaling. Our pilot data therefore suggest that analgesic and anxiolytic effects are instantiated in distinguishable neural mechanisms and differ between distinct stress- and pain-modulatory approaches, supporting the recent notion of multiple pathways subserving top-down modulation of the pain experience. Additional studies in larger cohorts are needed to follow up on these preliminary findings.
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    Variability in conditioned pain modulation predicts response to NSAID treatment in patients with knee osteoarthritis
    (BioMed Central, 2016) Edwards, Robert; Dolman, Andrew J.; Martel, Marc. O.; Finan, Patrick H.; Lazaridou, Asimina; Cornelius, Marise; Wasan, Ajay D.
    Background: Patients with painful knee osteoarthritis (OA) demonstrate hyperalgesia and altered pain-modulatory responses. While some prior work has demonstrated cross-sectional associations between laboratory and clinical pain measures, it is unknown whether individual variability in quantitative sensory testing (QST) responses at baseline can prospectively predict analgesic treatment responses. Method Patients with knee OA (n = 35) were compared on QST responses to a demographically-matched pain-free control group (n = 39), after which patients completed a month-long treatment study of diclofenac sodium topical gel (1 %), applied up to 4 times daily. Results: OA patients demonstrated reduced pain thresholds at multiple anatomic sites, as well as reduced conditioned pain modulation (CPM) and enhanced temporal summation of pain. The most pain-sensitive patients tended to report the most intense and neuropathic OA pain. Following diclofenac treatment, the knee OA cohort showed a roughly 30 % improvement in pain, regardless of the presence or absence of neuropathic symptoms. Baseline CPM scores, an index of endogenous pain-inhibitory capacity, were prospectively associated with treatment-related changes in clinical pain. Specifically, participants with higher CPM at baseline (i.e., better functioning endogenous pain-inhibitory systems) showed more reduction in pain at the end of treatment (p < .05). Conclusions: These results support prior findings of amplified pain sensitivity and reduced pain-inhibition in OA patients. Moreover, the moderate to strong associations between laboratory-based measures of pain sensitivity and indices of clinical pain highlight the clinical relevance of QST in this sample. Finally, the prospective association between CPM and diclofenac response suggests that QST-based phenotyping may have utility in explaining inter-patient variability in long-term analgesic treatment outcomes. Trial registration ClinicalTrials.Gov Identifier: NCT01383954. Registered June 22, 2011.
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    Well-Loved Music Robustly Relieves Pain: A Randomized, Controlled Trial
    (Public Library of Science, 2014) Hsieh, Christine; Kong, Jian; Kirsch, Irving; Edwards, Robert; Jensen, Karin B.; Kaptchuk, Ted; Gollub, Randy
    Music has pain-relieving effects, but its mechanisms remain unclear. We sought to verify previously studied analgesic components and further elucidate the underpinnings of music analgesia. Using a well-characterized conditioning-enhanced placebo model, we examined whether boosting expectations would enhance or interfere with analgesia from strongly preferred music. A two-session experiment was performed with 48 healthy, pain experiment-naïve participants. In a first cohort, 36 were randomized into 3 treatment groups, including music enhanced with positive expectancy, non-musical sound enhanced with positive expectancy, and no expectancy enhancement. A separate replication cohort of 12 participants received only expectancy-enhanced music following the main experiment to verify the results of expectancy-manipulation on music. Primary outcome measures included the change in subjective pain ratings to calibrated experimental noxious heat stimuli, as well as changes in treatment expectations. Without conditioning, expectations were strongly in favor of music compared to non-musical sound. While measured expectations were enhanced by conditioning, this failed to affect either music or sound analgesia significantly. Strongly preferred music on its own was as pain relieving as conditioning-enhanced strongly preferred music, and more analgesic than enhanced sound. Our results demonstrate the pain-relieving power of personal music even over enhanced expectations. Trial Information Clinicaltrials.gov NCT01835275.
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    The Lateral Prefrontal Cortex Mediates the Hyperalgesic Effects of Negative Cognitions in Chronic Pain Patients
    (Elsevier BV, 2015) Loggia, Marco; Berna, Chantal; Kim, Jieun; Cahalan, Christine M.; Martel, Marc-Olivier; Gollub, Randy; Wasan, Ajay D.; Napadow, Vitaly; Edwards, Robert
    While high levels of negative affect and cognitions have been associated in chronic pain conditions with greater pain sensitivity, the neural mechanisms mediating the hyperalgesic effect of psychological factors in patients with pain disorders are largely unknown. In this cross-sectional study, we hypothesized that 1) catastrophizing modulates brain responses to pain anticipation, and that 2) anticipatory brain activity mediates the hyperalgesic effect of different levels of catastrophizing, in fibromyalgia (FM) patients. Using functional Magnetic Resonance Imaging, we scanned the brains of 31 FM patients exposed to visual cues anticipating the onset of moderately intense deep-tissue pain stimuli. Our results indicated the existence of a negative association between catastrophizing and pain-anticipatory brain activity, including in the right lateral prefrontal cortex (IPFC). A bootstrapped mediation analysis revealed that pain-anticipatory activity in lateral prefrontal cortex (IPFC) mediates the association between catastrophizing and pain sensitivity. These findings highlight the role of IPFC in the pathophysiology of FM related hyperalgesia, and suggest that deficits in the recruitment of pain-inhibitory brain circuitry during pain-anticipatory periods may play an important contributory role in the association between various degrees of widespread hyperalgesia in FM and levels of catastrophizing, a well validated measure of negative cognitions and psychological distress. Perspective This article highlights the presence of alterations in pain-anticipatory brain activity in FM. These findings provide the rationale for the development of psychological or neurofeedback-based techniques aimed at modifying patients' negative affect and cognitions towards pain.