Pain
-
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.
-
Extracellular high mobility group box-1 protein (HMGB1) plays important roles in the pathogenesis of nerve injury- and cancer-induced pain. However, the involvement of spinal HMGB1 in arthritis-induced pain has not been examined previously and is the focus of this study. Immunohistochemistry showed that HMGB1 is expressed in neurons and glial cells in the spinal cord. ⋯ Furthermore, the pro-nociceptive effect of i.t. injection of HMGB1 persisted in Tlr2- and Rage-, but was absent in Tlr4-deficient mice. The same pattern was observed for HMGB1-induced spinal microglia and astrocyte activation and cytokine induction. These results demonstrate that spinal HMGB1 contributes to nociceptive signal transmission via activation of TLR4 and point to disulfide HMGB1 inhibition as a potential therapeutic strategy in treatment of chronic inflammatory pain.
-
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.
-
Missing data in clinical trials can bias estimates of treatment effects. Statisticians and government agencies recommend making every effort to minimize missing data. Although statistical methods are available to accommodate missing data, their validity depends on often untestable assumptions about why the data are missing. ⋯ Last observation carried forward imputation was used most commonly (42%). Thirteen articles reported more than 1 method to accommodate missing data; however, the majority of methods, including last observation carried forward, were not methods currently recommended by statisticians. Authors, reviewers, and editors should prioritize proper reporting of missing data and appropriate use of methods to accommodate them so as to improve the deficiencies identified in this systematic review.