The journal of pain : official journal of the American Pain Society
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We have previously established a thrombus-induced ischemic pain (TIIP) model in the rat, which mimics the pathophysiology of ischemic pain in patients with peripheral arterial disease. Because ischemia commonly induces acidosis and ATP release, one of the goals of this study was to investigate the role of acid-sensing ion channels (ASICs), transient receptor potential vanilloid-1 (TRPV1) receptors, and P2X receptors in the maintenance of ischemia-induced mechanical allodynia (MA). To test this, amiloride (an ASIC blocker), AMG-9810 (a TRPV1 blocker), or PPADS (a P2Xs antagonist) was intraplantarly injected at day 3 after FeCl(2) application onto the femoral artery. Ipsilateral administration of amiloride or PPADS but not AMG-9810 dose-dependently reduced MA. However, contralateral amiloride or PPADS did not suppress contralateral MA. Interestingly, co-administration of submaximal doses of amiloride and PPADS produced a significantly prolonged suppression of MA. Furthermore, ipsilateral EGTA (a calcium chelator) or chelerythrine (a protein kinase C inhibitor) also significantly reduced MA. Collectively, these findings suggest that peripheral ASICs and P2X receptors are involved in the maintenance of TIIP, which is possibly mediated by a Ca(2+)-protein kinase C signaling mechanism. These results provide mechanistic information about peripheral ischemic nociception that may be useful for developing better therapeutic management of ischemic pain in patients with peripheral arterial disease. ⋯ The results of the current study demonstrate that peripheral administration of an ASICs blocker or P2X antagonist significantly suppress TIIP. Co-administration of submaximal doses of ASIC and P2X antagonists produced an even greater effect. These results implicate peripheral ASICs and P2X receptors in the maintenance of thrombus-induced ischemic pain.
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Pain is a debilitating condition affecting millions each year, yet what predisposes certain individuals to be more sensitive to pain remains relatively unknown. Several psychological factors have been associated with pain perception, but the structural relations between multiple higher- and lower-order constructs and pain are not well understood. Thus, we aimed to examine the associations between pain perception using the cold pressor task (CPT), higher-order personality traits (neuroticism, negative affectivity, trait anxiety, extraversion, positive affectivity, psychoticism), and lower-order pain-related psychological constructs (pain catastrophizing [pre- and post-], fear of pain, anxiety sensitivity, somatosensory amplification, hypochondriasis) in 66 pain-free adults. Factor analysis revealed 3 latent psychological variables: pain- or body-sensitivity, negative affect/neuroticism, and positive affect/extraversion. Similarly, pain responses factored into 3 domains: intensity, quality, and tolerance. Regression and correlation analyses demonstrated that: 1) all the lower-order pain constructs (fear, catastrophizing, and hypochondriasis) are related through a single underlying latent factor that is partially related to the higher-order negative-valence personality traits; 2) pain- or body-sensitivity was more strongly predictive of pain quality than higher-order traits; and 3) the form of pain assessment is important-only qualitative pain ratings were significantly predicted by the psychological factors. ⋯ Consistent with the biopsychosocial model, these results suggest multiple pain-related psychological measures likely assess a common underlying factor, which is more predictive of qualitative than intensity pain ratings. This information may be useful for the development and advancement of pain assessments and treatments while considering the multidimensional nature of pain.
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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.