The journal of pain : official journal of the American Pain Society
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We previously showed evidence for a genetic association of the human leukocyte antigen (HLA) system and complex regional pain syndrome (CRPS) with dystonia. Involvement of the HLA system suggests that CRPS has a genetic component with perturbed regulation of inflammation and neuroplasticity as possible disease mechanisms. However, it is at present unclear whether the observed association with HLA-B62 and HLA-DQ8 in CRPS patients with dystonia also holds true for patients without dystonia. Therefore, we tested the possible association with HLA-B62 and HLA-DQ8 in a clinically homogeneous group of 131 CRPS patients without dystonia. In addition, we investigated the possible association with other alleles of the HLA-A, HLA-B, HLA-C, HLA-DR, and HLA-DQ loci. We showed an increased prevalence of HLA-DQ8 (molecularly typed as HLA-DQB1*03:02; OR = 1.65 [95% CI 1.12-2.42], P = .014) in CRPS without dystonia, whereas no association was observed for HLA-B62 (molecularly typed as HLA-B*15:01; OR = 1.22 [95% CI .78-1.92], P = .458). Our data suggest that CRPS with and CRPS without dystonia may be genetically different, but overlapping, disease entities because only HLA-DQ8 is associated with both. The findings also indicate that distinct biological pathways may play a role in both CRPS subtypes. ⋯ This study is the first to replicate a specific HLA region conferring genetic risk for the development of CRPS. Moreover, associations of HLA-DQ8 with both CRPS with and CRPS without dystonia, and HLA-B62 only with CRPS with dystonia, suggest that these disease entities may be genetically different, but overlapping.
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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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Pain is a multidimensional phenomenon. Previous psychological studies have shown that a person's subjective pain threshold can change when certain emotions are recognized. We examined this association with magnetoencephalography. Magnetic field strength was recorded with a 306-channel neuromagnetometer while 19 healthy subjects (7 female, 12 male; age range = 20-30 years) experienced pain stimuli in different emotional contexts induced by the presentation of sad, happy, or neutral facial stimuli. Subjects also rated their subjective pain intensity. We hypothesized that pain stimuli were affected by sadness induced by facial recognition. We found: 1) the intensity of subjective pain ratings increased in the sad emotional context compared to the happy and the neutral contexts, and 2) event-related desynchronization of lower beta bands in the right hemisphere after pain stimuli was larger in the sad emotional condition than in the happy emotional condition. Previous studies have shown that event-related desynchronization in these bands could be consistently observed over the primary somatosensory cortex. These findings suggest that sadness can modulate neural responses to pain stimuli, and that brain processing of pain stimuli had already been affected, at the level of the primary somatosensory cortex, which is critical for sensory processing of pain. ⋯ We found that subjective pain ratings and cortical beta rhythms after pain stimuli are influenced by the sad emotional context. These results may contribute to understanding the broader relationship between pain and negative emotion.
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Due to high profile initiatives at the national level, awareness of inadequate pain care affecting many groups in our society has never been greater. Nevertheless, increased awareness of pain disparities and the initiatives to address these disparities have yielded only modest progress, most notably in the form of growing appreciation that pain disparities likely result from multiple factors, including biological, psychological, environmental, health system, and cultural factors. Much less progress has been made in developing interventions that target these multiple determinants to reduce pain management disparities. In this paper we discuss key ethical and methodological challenges that undermine our capacity to investigate and develop meaningful interventions to improve pain outcomes among vulnerable populations. Key challenges in the areas of research engagement, recruitment, design, and measurement are discussed from both scientific and normative standpoints. Specific opportunities within emerging research paradigms to improve designs and measures are also discussed. Finally, we conclude with identifying potential synergies between the pain management disparities research agenda and the broader areas of clinical practice, advocacy, and policy that could help to move the field forward. ⋯ Researchers studying disparities in pain care face a number of ethical and methodological challenges that must be addressed to advance the field towards eliminating disparities. We discuss these ethical and methodological challenges and propose opportunities for paradigmatic revisions in areas of research engagement, design, measurement, advocacy, and policy.