Pain
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Randomized Controlled Trial
Combination analgesic development for enhanced clinical efficacy (the CADENCE trial): a double-blind, controlled trial of an alpha-lipoic acid-pregabalin combination for fibromyalgia pain.
Drug therapy for fibromyalgia is limited by incomplete efficacy and dose-limiting adverse effects (AEs). Combining agents with complementary analgesic mechanisms-and differing AE profiles-could provide added benefits. We assessed an alpha-lipoic acid (ALA)-pregabalin combination with a randomized, double-blind, 3-period crossover design. ⋯ Alpha-lipoic acid and pregabalin maximal tolerated doses were similar during combination and monotherapy, and AEs were not frequent with combination therapy. These results do not support any additive benefit of combining ALA with pregabalin for fibromyalgia. The observation of similarly reached maximal tolerated drug doses of these 2 agents (which have differing side-effect profiles) during combination and monotherapy-without increased side effects-provides support for future development of potentially more beneficial combinations with complementary mechanisms and nonoverlapping side effects.
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Meta Analysis
Effect modifiers of virtual reality in pain management: a systematic review and meta-regression analysis.
There is a rapidly growing body of evidence for the application of virtual reality (VR) in pain management, however, with varying effectiveness. Little is known about patient-related and VR-related factors affecting efficacy of VR. A systematic review and meta-analysis was performed including 122 randomised controlled trials (9138 patients), reporting on subjectively reported pain scores comparing an immersive VR intervention to a non-VR control group. ⋯ Heterogeneity was considerable for all meta-analyses, and risk of bias was moderate to high in most included studies. Studies on mechanisms behind VR analgesia in younger patients and patients reporting moderate to severe pain are recommended to confirm our hypotheses while taking into account risk of bias and the comparator. Optimal application of VR using treatment modules for long-term pain conditions are an important issue for future research.
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Multicenter Study
Heart rate variability is not suitable as surrogate marker for pain intensity in patients with chronic pain.
The search towards more objective outcome measurements and consequently surrogate markers for pain started decades ago; however, no generally accepted biomarker for pain has qualified yet. The goal is to explore the value of heart rate variability (HRV) as surrogate marker for pain intensity chronic pain setting. Pain intensity scores and HRV were collected in 366 patients with chronic pain, through a cross-sectional multicenter study. ⋯ The highest surrogacy point estimate was found for mean heart rate as marker for average pain intensity on the numeric rating scale with point estimates of 0.0961 (95% confidence interval [CI] 0.0384-0.1537) and 0.0209 (95% CI 0-0.05) for patients without medication use and with medication, respectively. This study indicated that HRV parameters as separate entities are no suitable surrogacy candidates for pain intensity, in a population of chronic pain patients. Further potential surrogate candidates and clinical robust true endpoints should be explored, to find a surrogate measure for the highly individual pain experience.
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Chronic pain and mental health problems have both been identified as public health emergencies and co-occur at high rates. This prospective, longitudinal investigation examined whether chronic pain status, pain-related symptoms (intensity, interference), pain catastrophizing, and insomnia severity predicted first lifetime onset of depressive and/or anxiety disorders as well as suicidality in a cohort of youth with a parental history of mood and/or anxiety disorders. Participants included 145 youth ( Mage = 13.74 years; 64% female) who completed structured diagnostic interviews at baseline and at 9- and 18-month follow-up to assess depressive and anxiety disorders as well as suicidality. ⋯ Increased pain intensity and interference at baseline predicted increased severity of suicidality at follow-up. Insomnia severity predicted increased likelihood of anxiety disorder onset. The presence of chronic pain and elevated pain-related symptoms and insomnia are premorbid risk factors for the development of significant mental health disorders and issues in youth.
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Chronic pain is a prevalent disease with increasing clinical challenges. Genome-wide association studies in chronic pain patients have identified hundreds of common pathogenic variants, yet they only explained a portion of individual variance of chronic pain. With the advances in next-generation sequencing technologies, it is now feasible to conduct rarer variants studies in large-scale databases. ⋯ These 2 rare variants were then tested for replication in 3 other biobanks, and the strongest evidence was found for rs28364172 as an individual contributor. Transcriptional analyses of Slc13a1 in rodents showed substantial regulation of its expression in the dorsal root ganglia and the sciatic nerve in neuropathic pain assays. Our results stress the importance of the SLC13A1 gene in sulfate homeostasis in the nervous system and its critical role in preventing pain states, thus suggesting new therapeutic approaches for treating chronic pain in a personalized manner, especially in people with mutations in the SLC13A1 gene.