Pain
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Randomized Controlled Trial Multicenter Study
A phase 3, multi-center, randomized, double-blind, placebo-controlled, safety, tolerability, and efficacy study of Xtampza ERTM in patients with moderate-to-severe chronic low back pain.
Opioid analgesics are commonly used for the treatment of chronic low back pain (CLBP); however, abuse potential is a major concern. This study used a randomized, double-blind, placebo-controlled, enriched-enrollment randomized-withdrawal study design to evaluate the safety, tolerability, and analgesic efficacy of an abuse-deterrent formulation of extended-release oxycodone, Xtampza ER, in opioid-naive and opioid-experienced adults with moderate-to-severe CLBP. Patients entered an open-label titration phase (N = 740); those who were successfully titrated on Xtampza ER (≥40 to ≤160 mg oxycodone hydrochloride equivalent per day) were randomized to active drug (N = 193) or placebo (N = 196) for 12 weeks. ⋯ There was less rescue medication (acetaminophen) use in the Xtampza ER treatment group than in the placebo group. Xtampza ER had an adverse event profile consistent with other opioids and was well tolerated; no new safety concerns were identified. In conclusion, Xtampza ER resulted in clinically and statistically significant efficacy in patients with CLBP.
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Recent failures of clinical trials of novel analgesics designed to treat neuropathic pain have led to much speculation about the underlying reasons. One often discussed possibility is that the placebo response in these trials has increased in recent years, leading to lower separation between the drug and placebo arms. Whether this has indeed occurred has not yet been adequately addressed. ⋯ Consideration of participant and study characteristics revealed that in the United States but not elsewhere, RCTs have increased in study size and length. These changes are associated with larger placebo response. Analysis of individual RCT time courses showed different kinetics for the treatment vs placebo responses, with the former evolving more quickly than the latter and plateauing, such that maximum treatment advantage was achieved within 4 weeks.
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Randomized Controlled Trial
Preoperative dexamethasone reduces acute but not sustained pain after lumbar disc surgery: a randomized, blinded, placebo-controlled trial.
Glucocorticoids have attracted increasing attention as adjuvants in the treatment of acute postoperative pain. Furthermore, anecdotal reports may support glucocorticoids for preventing sustained postoperative pain. We explored preoperative dexamethasone combined with paracetamol and ibuprofen on acute and sustained pain after lumbar disk surgery. ⋯ Sixteen percent (95% CI 7-26) vs 8% (95% CI 0-17) reported new weakness/paralysis of the legs in the dexamethasone and placebo groups, respectively, 3 months postoperatively (P = 0.20). In conclusion, preoperative dexamethasone significantly reduced pain during mobilization and vomiting, after lumbar disk surgery. No significant effects were observed 3 months postoperatively.
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Offset analgesia (OA) is a form of endogenous pain inhibition characterized by a disproportionately large reduction in pain perception after a small decrease in temperature during noxious thermal stimulation. In this study, the presence of OA was evaluated in patients with fibromyalgia and compared with healthy age-matched and sex-matched controls. Offset analgesia was induced by noxious thermal stimulation on the arm, causing a visual analog score (VAS) of about 50 mm, followed by a 1°C temperature decrease. ⋯ Decreased OA responses were not enhanced or restored by repeating the OA paradigm or by the downward step test. Defective engagement of OA had a significant effect on pain onset, as observed from the upward OA step test, with less tolerability to noxious pain stimulation in patients with fibromyalgia. In conclusion, patients with fibromyalgia showed less pain inhibition as measured by the OA paradigm, which influenced both the onset and offset of pain.