Pain
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Randomized Controlled Trial
Tanezumab for chronic low back pain: a randomized, double-blind, placebo- and active-controlled, phase 3 study of efficacy and safety.
This randomized, double-blind, phase 3 study (56-week treatment; 24-week follow-up) assessed tanezumab in patients with chronic low back pain and history of inadequate response to standard-of-care analgesics (NCT02528253). Patients received placebo, subcutaneous tanezumab (5 or 10 mg every 8 weeks), or oral tramadol prolonged-release (100-300 mg/day). Primary endpoint was change in low back pain intensity (LBPI) at week 16 for tanezumab vs placebo. ⋯ Seven patients, all in the tanezumab 10 mg group (1.4%), underwent total joint replacement. In conclusion, tanezumab 10 mg significantly improved pain and function vs placebo in patients with difficult-to-treat chronic low back pain. Tanezumab was associated with a low rate of joint safety events, some requiring joint replacement.
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Randomized Controlled Trial
A randomized, double-blind, placebo-controlled study of daily cannabidiol for the treatment of canine osteoarthritis pain.
Over the last 2 decades, affirmative diagnoses of osteoarthritis (OA) in the United States have tripled due to increasing rates of obesity and an aging population. Hemp-derived cannabidiol (CBD) is the major nontetrahydrocannabinol component of cannabis and has been promoted as a potential treatment for a wide variety of disparate inflammatory conditions. Here, we evaluated CBD for its ability to modulate the production of proinflammatory cytokines in vitro and in murine models of induced inflammation and further validated the ability of a liposomal formulation to increase bioavailability in mice and in humans. ⋯ Liposomal CBD (20 mg/day) was as effective as the highest dose of nonliposomal CBD (50 mg/day) in improving clinical outcomes. Hematocrit, comprehensive metabolic profile, and clinical chemistry indicated no significant detrimental impact of CBD administration over the 4-week analysis period. This study supports the safety and therapeutic potential of hemp-derived CBD for relieving arthritic pain and suggests follow-up investigations in humans are warranted.
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Pain is a principal contributor to the global burden of arthritis with peripheral sensitization being a major cause of arthritis-related pain. Within the knee joint, distal endings of dorsal root ganglion neurons (knee neurons) interact with fibroblast-like synoviocytes (FLS) and the inflammatory mediators they secrete, which are thought to promote peripheral sensitization. ⋯ Electrophysiological recordings from retrograde labelled knee neurons cocultured with TNF-FLS, or supernatant derived from TNF-FLS, revealed a depolarized resting membrane potential, increased spontaneous action potential firing, and enhanced TRPV1 function, all consistent with a role for FLS in mediating the sensitization of pain-sensing nerves in arthritis. Therefore, data from this study demonstrate the ability of FLS activated by TNF-α to promote neuronal sensitization, results that highlight the importance of both nonneuronal and neuronal cells to the development of pain in arthritis.
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One of the potential mechanisms of motor cortex stimulation by noninvasive brain stimulation (NIBS) effects on pain is through the restoration of the defective endogenous inhibitory pain pathways. However, there are still limited data on quantitative sensory testing (QST), including conditioned pain modulation (CPM), supporting this mechanism. This systematic review and meta-analysis aimed to evaluate the effects of noninvasive motor cortex stimulation on pain perception as indexed by changes in QST outcomes. ⋯ Thirty-eight studies were included (1178 participants). We found significant increases of pain threshold in healthy subjects (ES = 0.16, 95% CI = 0.02-0.31, I2 = 22.2%) and pain populations (ES = 0.48, 95% CI = 0.15-0.80, I2 = 68.8%), and homogeneous higher CPM effect (pain ratings reduction) in healthy subjects (ES = -0.39, 95% CI = -0.64 to -0.14, I2 = 17%) and pain populations (ES = -0.35, 95% CI = -0.60 to -0.11, I2 = 0%) in the active NIBS group compared with sham. These results support the idea of top-down modulation of endogenous pain pathways by motor cortex stimulation as one of the main mechanisms of pain reduction assessed by QST, which could be a useful predictive and prognostic biomarker for chronic pain personalized treatment with NIBS.