Pain
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Randomized Controlled Trial Comparative Study
Biased agonism of the mu opioid receptor by TRV130 increases analgesia and reduces on-target adverse effects versus morphine: a randomized, double-blind placebo-controlled crossover study in healthy volunteers.
Opioids provide powerful analgesia but also efficacy-limiting adverse effects, including severe nausea, vomiting, and respiratory depression, by activating μ-opioid receptors. Preclinical models suggest that differential activation of signaling pathways downstream of these receptors dissociates analgesia from adverse effects; however, this has not yet translated to a treatment with an improved therapeutic index. Thirty healthy men received single intravenous injections of the biased ligand TRV130 (1.5, 3, or 4.5mg), placebo, or morphine (10mg) in a randomized, double-blind, crossover study. ⋯ TRV130 was generally well tolerated, and exposure was dose proportional. Thus, in this study, TRV130 produced greater analgesia than morphine at doses with less reduction in respiratory drive and less severe nausea. This demonstrates early clinical translation of ligand bias as an important new concept in receptor-targeted pharmacotherapy.
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Randomized Controlled Trial Multicenter Study
Nurse Practitioners can effectively deliver Pain Coping Skills Training to osteoarthritis patients with chronic pain: A randomized, controlled trial.
A multisite, randomized, controlled clinical effectiveness trial was conducted for osteoarthritis patients with chronic pain of the knee or hip. Adult health nurse practitioners provided a 10-session intervention, pain coping skills training (PCST), in patients' doctors' offices (N=129 patients); the control group received usual care (N=127 patients). Primary outcomes assessed at baseline, posttreatment, 6-month follow-up, and 12-month follow-up were: pain intensity, physical functioning, psychological distress, self-efficacy, catastrophizing, use of coping strategies, and quality of life. ⋯ Per-protocol analyses did not yield greater effect sizes. Comparisons of PCST patients who were more vs less treatment adherent suggested greater effectiveness for patients with high adherence. Results support the effectiveness of nurse practitioner delivery of PCST for chronic osteoarthritis pain.
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Randomized Controlled Trial Multicenter Study
Long-term safety and effectiveness of tanezumab as treatment for chronic low back pain.
A noncontrolled, randomized, multicenter study (NCT00924664) evaluated long-term safety and effectiveness of tanezumab in patients with chronic low back pain following a randomized placebo- and active-controlled parent study that evaluated analgesic efficacy. Patients were randomized to tanezumab 10mg (n=321) or 20mg (n=527) administered at 8-week intervals via 3 intravenous injections followed by 4 subcutaneous injections. Effectiveness analyses included change from parent study baseline in Brief Pain Inventory Short Form, Roland Morris Disability Questionnaire, and Patient's Global Assessment of low back pain. ⋯ A blinded, independent adjudication committee reviewed all 6 patients with reported osteonecrosis and 4 of the 9 patients undergoing TJR. Adjudication outcomes were osteonecrosis (n=0), worsening osteoarthritis (n=5; 1 rapidly progressive), and another diagnosis or indeterminate (n=5). Tanezumab 10mg had better tolerability than tanezumab 20mg, and may represent an effective long-term treatment for chronic low back pain.