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Introduction: Lumbosacral radiculopathy (LR), also known as sciatica, is a common type of radiating neurologic pain involving burning, tingling, and numbness in the lower extremities. It has an estimated lifetime prevalence as high as 43%. Objectives: The objective of this randomized controlled trial was to evaluate the impact of virtually delivered Mindfulness-Oriented Recovery Enhancement (MORE) on patients with LR during the COVID-19 pandemic. Methods: Potentially eligible patients were identified using electronic health record queries and phone screenings. Participants were then randomized to MORE or treatment-as-usual (TAU) for 8 weeks, with pain intensity assessed daily. At baseline and follow-up visits, participants completed questionnaires assessing the primary outcome, disability, as well as quality of life, depression, mindful reinterpretation of pain, and trait mindfulness. Results: In our study, patients undergoing virtual delivery of MORE had greater improvements in daily pain intensity (P = 0.002) but not in disability (P = 0.09), depression (P = 0.26), or quality of life (P = 0.99 and P = 0.89, SF-12 physical and mental component scores, respectively), relative to TAU patients. In addition, patients in MORE experienced significantly greater increases in mindful reinterpretation of pain (P = 0.029) and trait mindfulness (P = 0.035). Conclusion: Among patients with lumbar radiculopathy, MORE significantly reduced daily pain intensity but did not decrease disability or depression symptoms. Given the long duration of symptoms in our sample, we hypothesize the discrepancy between changes in daily pain intensity and disability is due to fear avoidance behaviors common in patients with chronic pain. As the first trial of a mindfulness intervention in patients with LR, these findings should inform future integrative approaches to LR treatment, particularly when considering the increasing use of virtual interventions throughout the COVID-19 pandemic.
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Introduction: Centella asiatica is an herbaceous plant reputed in Eastern medicine to improve memory. Preclinical studies have shown that C. asiatica aqueous extract (CAW) improves neuronal health, reduces oxidative stress, and positively impacts learning and cognition. This study aimed to develop and validate bioanalytical methods for detecting known bioactive compounds from C. asiatica in human biological matrices and apply them to a human pharmacokinetic trial in healthy older adults. Methods: High performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was used for detecting triterpenes and caffeoylquinic acids from C. asiatica, or their metabolites, in human plasma and urine. Validation parameters including linearity, precision, accuracy, recovery and thermal stability were evaluated. The method was applied to a Phase I, randomized, double-blind, crossover trial of two doses (2 or 4 g) of a standardized C. asiatica water extract product (CAP) in eight healthy older adults. Pharmacokinetic parameters were measured over a 12-h post administration period and acute safety was assessed. Results: The method satisfied US Food & Drug Administration criteria for linearity and recovery of the analytes of interest in human plasma and urine. The method also satisfied criteria for precision and accuracy at medium and high concentrations. Single administration of 2 and 4 g of CAP was well tolerated and safe in healthy older adults. The parent triterpene glycosides, asiaticoside and madecassoside, were not detected in plasma and in minimal amounts in urinary excretion analyses, while the aglycones, asiatic acid and madecassic acid, showed readily detectable pharmacokinetic profiles. Similarly, the di-caffeoylquinic acids and mono-caffeoylquinic acids were detected in low quantities, while their putative metabolites showed readily detectable pharmacokinetic profiles and urinary excretion. Discussion: This method was able to identify and calculate the concentration of triterpenes and caffeoylquinic acids from C. asiatica, or their metabolites, in human plasma and urine. The oral absorption of these key compounds from CAP, and its acute safety in healthy older adults, support the use of this C. asiatica product in future clinical trials.
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Introduction: Lumbosacral radiculopathy/radiculitis (LR) or "sciatica" is a commonly intractable sequelae of chronic low back pain (LBP), and challenges in the treatment of LR indicate that persistent pain may have both mechanical and neuropathic origins. Mindfulness-based interventions have been demonstrated to be effective tools in mitigating self-reported pain in LBP patients. This paper describes the protocol for a randomized controlled trial (RCT) evaluating the effects of the specific mindfulness-based intervention Mindfulness-Oriented Recovery Enhancement (MORE) on LR symptoms and sequelae, including mental health and physical function. Methods: Participants recruited from the Portland, OR area are screened before completing a baseline visit that includes a series of self-report questionnaires and surface electromyography (sEMG) of the lower extremity. Upon enrollment, participants are randomly assigned to the MORE (experimental) group or treatment as usual (control) group for 8 weeks. Self-reported assessments and sEMG studies are repeated after the intervention is complete for pre/post-intervention comparisons. The outcome measures evaluate self-reported pain, physical function, quality of life, depression symptoms, trait mindfulness, and reinterpretation of pain, with surface electromyography (sEMG) findings evaluating objective physical function in patients with LR. To our knowledge, this is the first trial to date using an objective measure, sEMG, to evaluate the effects of a mindfulness-based intervention on LR symptoms. Hypotheses: We hypothesize that MORE will be effective in improving self-reported pain, physical function, quality of life, depression symptoms, mindfulness, and reinterpretation of pain scores after 8 weeks of mindfulness training as compared to treatment as usual. Additionally, we hypothesize that individuals in the MORE group with abnormal sEMG findings at baseline will have improved sEMG findings at their 8-week follow-up visit.
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Centella asiatica is reputed in Eastern medicine to improve cognitive function in humans. Preclinical studies have demonstrated that aqueous extracts of C. asiatica improve cognition in mouse models of aging and Alzheimer's disease (AD) through the modulation of mitochondrial biogenesis and nuclear factor-erythroid-2-related factor 2 (Nrf2)-dependent antioxidant response genes. This randomized, double-blind, crossover Phase I trial explored the oral bioavailability and pharmacokinetics of key compounds from two doses (2 g and 4 g) of a standardized C. asiatica aqueous extract product (CAP), over 10 h, in four mildly demented older adults on cholinesterase inhibitor therapy. The analysis focused on triterpenes (TTs) and caffeoylquinic acids (CQAs), which are known to contribute to C. asiatica's neurological activity. The acute safety of CAP and the effects on NRF2 gene expression in peripheral blood mononuclear cells were evaluated. Single administration of 2 g or 4 g of CAP was safe and well-tolerated. The TT aglycones, asiatic acid and madecassic acid, were identified in plasma and urine, while the parent glycosides, asiaticoside and madecassoside, although abundant in CAP, were absent in plasma and had limited renal excretion. Similarly, mono- and di-CQAs showed delayed absorption and limited presence in plasma or urine, while the putative metabolites of these compounds showed detectable plasma pharmacokinetic profiles and urinary excretion. CAP elicited a temporal change in NRF2 gene expression, mirroring the TT aglycone's pharmacokinetic curve in a paradoxical dose-dependent manner. The oral bioavailability of active compounds or their metabolites, NRF2 target engagement, and the acute safety and tolerability of CAP support the validity of using CAP in future clinical studies.