The journal of pain : official journal of the American Pain Society
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A cross-sectional nationwide epidemiological study was performed in a random sample of the Portuguese adult population, aiming to describe the prevalence and impact of chronic pain (CP). The 5,094 participants were selected by random digit dialing, between January 2007 and March 2008, and estimates were adequately weighted for the population. Prevalence of CP was 36.7% (95% confidence interval [CI] [35.3-38.2]), based on the definition of the International Association for the Study of Pain. Recurrent or continuous pain was present in 85% of those with CP, and moderate-to-severe intensity and disability were present in 68 and 35%, respectively. Highest CP prevalence was observed among the elderly, retired, unemployed, and less educated. Highest disability was found in relation with family/home responsibilities, recreational activities, occupation/work, and sleep/rest; 13% reported a diagnosis of depression and 49% reported interference in their job. The main factors associated with disability were sex, pain intensity, and depression or depressive symptoms. CP is highly prevalent, causes high personal and social burden, and affects particularly the most vulnerable subgroups. Portugal, depending on CP definition, could be placed in the lower prevalence group in Europe. Improvement in pain intensity management and special attention to affective components of CP are recommended. ⋯ In this cross-sectional nationwide epidemiological study, we showed that chronic pain is a significant problem that is present in 37% of the Portuguese adult general population, is associated with high personal, family, and social burden, and affects in particular the most vulnerable subgroups of the population.
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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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Randomized Controlled Trial
Respiration-induced hypoalgesia: exploration of potential mechanisms.
Slow breathing is used as a means to reduce pain, yet the mechanisms responsible for respiration-induced hypoalgesia are poorly understood. The present study asked 30 healthy participants (M(age) = 21 years, M(education) = 15 years, 80% white non-Hispanic) to breathe at normal, slow (50% normal), and fast (125% normal) rates while constant-intensity, suprathreshold electric stimulations were delivered to the sural nerve to elicit pain and the nociceptive flexion reflex (NFR, a measure of spinal nociception). Stimulations were equally balanced across inhalations and exhalations to determine whether parasympathetic activation during exhalations contributes to hypoalgesia. Respiration rate, heart rate variability (HRV, a measure of parasympathetic activity), heart rate, and subjective arousal were assessed as manipulation checks. Slow breathing reduced pain relative to normal breathing and fast breathing, but NFR was not influenced by breathing. Further, pain and NFR did not differ between exhalations and inhalations, and changes in HRV did not correlate with changes in pain or NFR. Together, these findings suggest that respiration-induced hypoalgesia does not require gating of spinal nociception or changes in parasympathetic activity. ⋯ Slow breathing reduced pain relative to normal and fast breathing. This respiration-induced hypoalgesia does not appear to be due to gating of spinal nociception or changes in parasympathetic activity.
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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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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.