The journal of pain : official journal of the American Pain Society
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The aim of the current study was to estimate the prevalence and time trend of invalidating musculoskeletal pain in the Spanish population and its association with socio-demographic factors, lifestyle habits, self-reported health status, and comorbidity with other diseases analyzing data from 1993-2006 Spanish National Health Surveys (SNHS). We analyzed individualized data taken from the SNHS conducted in 1993 (n = 20,707), 2001 (n = 21,058), 2003 (n = 21,650) and 2006 (n = 29,478). Invalidating musculoskeletal pain was defined as pain suffered from the preceding 2 weeks that decreased main working activity or free-time activity by at least half a day. We analyzed socio-demographic characteristics, self-perceived health status, lifestyle habits, and comorbid conditions using multivariate logistic regression models. Overall, the prevalence of invalidating musculoskeletal pain in Spanish adults was 6.1% (95% CI, 5.7-6.4) in 1993, 7.3% (95% CI, 6.9-7.7) in 2001, 5.5% (95% CI, 5.1-5.9) in 2003 and 6.4% (95% CI 6-6.8) in 2006. The prevalence of invalidating musculoskeletal pain among women was almost twice that of men in every year (P < .05). The multivariate analysis showed that occupational status (unemployed), sleep <8 hours/day and having any accident in the preceding year were significantly associated in both gender with a higher likelihood of suffering from invalidating musculoskeletal pain among Spanish adults. Within men, other predictors of invalidating musculoskeletal pain were to be married and lower educational level, whereas in women were age of 45-64 years old (OR 1.89, 95% CI 1.32-2.7), obesity (OR 1.23, 95% CI 1.06-1.42), a sedentary lifestyle (OR 1.23, 95% CI 1.06-1.42), and presence of comorbid chronic diseases (OR 1.32, 95% CI 1.14-1.53). Further, worse self-reported health status was also related to a greater prevalence of invalidating musculoskeletal pain (OR 6.88, 95% 5.62-8.40 men, OR 7.24, 95% 6.11-8.57 women). Finally, we found that the prevalence of invalidating musculoskeletal pain increased from 1993 to 2001 for both men (OR 1.31, 95% 1.08-1.58) and women (OR 1.19, 95% 1.03-1.39) with no significant increase from the remaining surveys. Our results suggest that invalidating musculoskeletal pain deserves an increased awareness among health professionals. More educational programs which address postural hygiene, physical exercise, and how to prevent obesity and sedentary lifestyle habits should be provided by Public Health Services. ⋯ This population-based study indicates that invalidating musculoskeletal pain that reduces main working activity is a public health problem in Spain. The prevalence of invalidating musculoskeletal pain was higher in women than in men and associated to lower income, poor sleeping, worse self-reported health status, and other comorbid conditions. Further, the prevalence of invalidating musculoskeletal pain increased from 1993 to 2001, but remained stable from the last years (2001 to 2006).
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We previously reported that endothelin A (ET-A) receptor antagonism attenuates carcinoma-induced pain in a cancer pain mouse model. In this study, we investigated the mechanism of ET-A receptor-mediated antinociception and evaluated the role of endogenous opioid analgesia. Squamous cell carcinoma (SCC) cell culture treated with the ET-A receptor antagonist (BQ-123) at 10(-6) M and 10(-5) M significantly increased production and secretion of beta-endorphin and leu-enkephalin, respectively. Behavioral studies were performed by inducing tumors in the hind paw of female nude mice with local injection of cells derived from a human oral SCC. Significant pain, as indicated by reduction in withdrawal thresholds in response to mechanical stimulation, began at 4 days after SCC inoculation and lasted to 18 days, the last day of measurement. Local administration of either naloxone methiodide (500 microg/kg), selective antagonists for mu-opioid receptor (CTOP, 500 microg/kg), or delta-opioid receptor (naltrindole, 11 mg/kg) but not kappa-opioid receptor (nor-BNI, 2.5 mg/kg) significantly reversed antinociception observed from ET-A receptor antagonism (BQ-123, 92 mg/kg) in cancer animals. These results demonstrate that antagonism of peripheral ET-A receptor attenuates carcinoma pain by modulating release of endogenous opioids to act on opioid receptors in the cancer microenvironment. ⋯ This article proposes a novel mechanism for ET-A receptor antagonist drugs in managing cancer-induced pain. An improved understanding of the role of innate opioid analgesia in ET-A receptor-mediated antinociception might provide novel alternatives to morphine therapy for the treatment of cancer pain.
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Review Meta Analysis Comparative Study
Comparative efficacy and harms of duloxetine, milnacipran, and pregabalin in fibromyalgia syndrome.
Duloxetine (DLX), milnacipran (MLN), and pregabalin (PGB) are the only drugs licensed by the US Food and Drug Administration (FDA) for fibromyalgia syndrome (FMS). Evidence on the comparative benefits and harms is still accruing. The authors searched MEDLINE, SCOPUS, Cochrane Central Register of Controlled Trials, and sought unpublished data from the databases of FDA, US National Institutes for Health, and Industry through May 2009 for randomized controlled trials. Outcomes of interest were symptom reduction (pain, fatigue, sleep disturbance, depressed mood, reduced health-related quality of life), and adverse events. 17 studies with 7,739 patients met the inclusion criteria. The 3 drugs were superior to placebo except DLX for fatigue, MLN for sleep disturbance, and PGB for depressed mood. Adjusted indirect comparisons indicated no significant differences for 30% pain relief and dropout rates due to adverse events between the 3 drugs. Significant differences in average symptom reduction were found: DLX and PGB were superior to MLN in reduction of pain and sleep disturbances. DLX was superior to MLN and PGB in reducing depressed mood. MLN and PGB were superior to DLX in reducing fatigue. The risk of headache and nausea with DLX and MLN was higher compared with PGB. The risk of diarrhea was higher with DLX compared to MLN and PGB. There is evidence for the short-term (up to 6 months) efficacy of DLX, MLN, and PGB. Differences with regard to the occurrence of the key symptoms of FMS and to drug-specific adverse events may be relevant for the choice of medication. ⋯ This article presents comparative data on the efficacy and harms of duloxetine, milnacipran, and pregabalin in fibromyalgia syndrome. The results can help clinicians in choosing medication since the 3 drugs have different effects on the key symptoms of fibromyalgia syndrome and differences in side effects, contraindications, and warnings.
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Randomized Controlled Trial
A randomized, controlled, open-label study of the long-term effects of NGX-4010, a high-concentration capsaicin patch, on epidermal nerve fiber density and sensory function in healthy volunteers.
Desensitization of nociceptive sensory nerve endings is the basis for the therapeutic use of capsaicin in neuropathic pain syndromes. This study evaluated the pharmacodynamic effects of a single 60-minute application of NGX-4010, a high-concentration (8% w/w) capsaicin patch, on both thighs of healthy volunteers. Epidermal nerve fiber (ENF) density and quantitative sensory testing (QST) using thermal, tactile, and sharp mechanical-pain (pinprick) stimuli were evaluated 1, 12 and 24 weeks after capsaicin exposure. After 1 week, there was about an 80% reduction of ENF density compared to unexposed sites. In addition, there was about an 8% increase in tactile thresholds compared to baseline and the proportion of stimuli reported as sharp mechanical pain decreased by about 15 percentage points. Twelve weeks after exposure to capsaicin, ENF regeneration was evident, but not complete, and sharp mechanical-pain sensation and tactile thresholds did not differ from unexposed sites. Nearly full (93%) ENF recovery was observed at 24 weeks. No statistically significant changes in heat- or cold-detection thresholds were observed at any time point. NGX-4010 was generally well tolerated. Transient, mild warming or burning sensations at the site of application were common adverse effects. ⋯ This article evaluates the effect of a single 60-minute NGX-4010 application on ENF density and QST in healthy volunteers followed for 24 weeks. The results help predict the long-term safety of NGX-4010 applications in patients.