The journal of pain : official journal of the American Pain Society
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Randomized Controlled Trial
Tanezumab reduces osteoarthritic knee pain: results of a randomized, double-blind, placebo-controlled phase III trial.
The objective of this study was to compare the analgesic efficacy of tanezumab versus placebo in patients with osteoarthritis (OA) of the knee. This was a 32-week, randomized, double-blind, placebo-controlled phase III trial (NCT00733902). The patient criteria included diagnosis of OA; Western Ontario and McMaster Universities OA Index (WOMAC) Pain and Physical Function subscale scores of ≥5 and ≥4, respectively; Patient's Global Assessment of Osteoarthritis (PGA) ≥3; and failure of nonopiate pain medications or candidacy for invasive interventions. Patients received 3 intravenous doses of tanezumab (2.5, 5, or 10 mg) or placebo. The co-primary efficacy end points were changes in WOMAC subscales and PGA at week 16. Adverse events were monitored throughout. Overall, 690 patients (61% female) were randomized and treated. Those treated with tanezumab showed significant improvement in the 3 co-primary end points (P ≤ .015 for all). The incidence of adverse events was 55 to 60% for tanezumab-treated patients versus 48% for placebo-treated patients. Joint replacement was reported in 4 patients, 1 in each treatment group; a total of 5 joints were replaced (1 index knee and 4 hips). The tanezumab OA clinical program is currently on clinical hold due to potential adverse reactions leading to joint replacement. ⋯ This is the first phase III randomized, controlled trial to demonstrate that nerve growth factor blockade by tanezumab has superior analgesic efficacy in OA of the knee compared with placebo. Tanezumab was well tolerated, and reports of worsening OA and/or joint replacement were evenly distributed across the treatment groups.
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In the present study, patients with musculoskeletal pain conditions (n = 55) were filmed while performing a lifting task designed to elicit pain behaviors. Patients were asked to perform the lifting task twice, under 2 distinct conditions. In the first condition, patients were asked to rate their pain while lifting a series of weights. In the second condition, patients were asked to estimate the weight of the objects they lifted. The weight estimation condition was conceived as a way to increase the cognitive load associated with the lifting task. The primary purpose of the present study was to examine whether manipulation of cognitive load differentially influenced the expression of pain behaviors in high and low catastrophizers. During the pain rating condition, results indicated that high catastrophizers displayed significantly higher levels of communicative and protective pain behaviors than low catastrophizers. During the weight estimation condition, however, high and low catastrophizers no longer differed in the expression of communicative pain behaviors. These results suggest that increasing cognitive load during a pain-eliciting task may interfere with the expression of communicative pain behaviors in high catastrophizers. The discussion addresses the potential role of automatic and cognitive control processes in the expression of pain behaviors. ⋯ The present study provides new insights into the processes that might underlie the expression of pain behaviors in patients with high levels of catastrophizing. Our findings could have implications for the management of patients presenting with pain conditions, particularly those with high levels of catastrophizing.
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Human and animal studies suggest that estrogens are involved in the processing of nociceptive sensory information and analgesic responses in the central nervous system. Rapid pronociceptive estrogenic effects have been reported, some of which likely involve G protein-coupled estrogen receptor (GPER) activation. Membrane depolarization and increases in cytosolic calcium and reactive oxygen species (ROS) levels are markers of neuronal activation, underlying pain sensitization in the spinal cord. Using behavioral, electrophysiological, and fluorescent imaging studies, we evaluated GPER involvement in spinal nociceptive processing. Intrathecal challenging of mice with the GPER agonist G-1 results in pain-related behaviors. GPER antagonism with G15 reduces the G-1-induced response. Electrophysiological recordings from superficial dorsal horn neurons indicate neuronal membrane depolarization with G-1 application, which is G15 sensitive. In cultured spinal sensory neurons, G-1 increases intracellular calcium concentration and induces mitochondrial and cytosolic ROS accumulation. In the presence of G15, G-1 does not elicit the calcium and ROS responses, confirming specific GPER involvement in this process. Cytosolic calcium concentration elevates faster and with higher amplitude following G-1 intracellular microinjections compared to extracellular exposure, suggesting subcellular GPER functionality. Thus, GPER activation results in spinal nociception, and the downstream mechanisms involve cytosolic calcium increase, ROS accumulation, and neuronal membrane depolarization. ⋯ Our results suggest that GPER modulates pain processing in spinal sensory neurons via cytosolic calcium increase and ROS accumulation. These findings extend the current knowledge on GPER involvement in physiology and disease, providing the first evidence of its pronociceptive effects at central levels and characterizing some of the underlying mechanisms.
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In 2008, according to the Medical Expenditure Panel Survey (MEPS), about 100 million adults in the United States were affected by chronic pain, including joint pain or arthritis. Pain is costly to the nation because it requires medical treatment and complicates treatment for other ailments. Also, pain lowers worker productivity. Using the 2008 MEPS, we estimated 1) the portion of total U.S. health care costs attributable to pain; and 2) the annual costs of pain associated with lower worker productivity. We found that the total costs ranged from $560 to $635 billion in 2010 dollars. The additional health care costs due to pain ranged from $261 to $300 billion. This represents an increase in annual per person health care costs ranging from $261 to $300 compared to a base of about $4,250 for persons without pain. The value of lost productivity due to pain ranged from $299 to $335 billion. We found that the annual cost of pain was greater than the annual costs of heart disease ($309 billion), cancer ($243 billion), and diabetes ($188 billion). Our estimates are conservative because they do not include costs associated with pain for nursing home residents, children, military personnel, and persons who are incarcerated. ⋯ This study estimates that the national cost of pain ranges from $560 to $635 billion, larger than the cost of the nation's priority health conditions. Because of its economic toll on society, the nation should invest in research, education, and training to advocate the successful treatment, management, and prevention of pain.
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Randomized Controlled Trial Multicenter Study Comparative Study
Comparative responsiveness of pain measures in cancer patients.
Brief measures to assess and monitor pain in cancer patients are available, but few head-to-head psychometric comparisons of different measures have been reported. Baseline and 3-month data were analyzed from 274 patients enrolled in the Indiana Cancer Pain and Depression (INCPAD) trial. Participants completed the Brief Pain Inventory (BPI), the PEG (a 3-item abbreviated version of the BPI), the short form (SF)-36 pain scale, and a pain global rating of change measure. The global rating was used as the criterion for standardized response mean and receiver operating characteristic curve analyses. To assess responsiveness to the trial intervention, we evaluated standardized effect size statistics stratified by trial arm. All measures were responsive to global improvement, discriminated between participants with and without improvement, and detected a significant intervention treatment effect. Short and longer measures were similarly responsive. Also, composite measures that combined pain severity and interference into a single score (BPI total, PEG, SF-36 pain) performed comparably to separate measures of each domain (BPI severity and BPI interference). ⋯ Pain measures as brief as 2 or 3 items that provide a single score are responsive in patients with cancer-related pain. Ultra-brief measures offer a valid and efficient means of assessing and monitoring pain for the clinical management as well as research of cancer-related pain.