Pain
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Comparative Study
Compared to limb pain of other origin, ultrasonographic osteodensitometry reveals loss of bone density in complex regional pain syndrome.
Local osteopenia and altered bone metabolism are major complications of complex regional pain syndrome (CRPS), but quantitative assessment is difficult unless using X-ray or dual-energy X-ray absorptiometry. Ultrasound-based measurement of bone density (UBD) is a possible alternative but has never been used to detect unilateral disease such as CRPS. Therefore, the main outcome measure of this prospective study was the diagnostic utility of UBD in patients with lower-limb CRPS. ⋯ Conversely, in patients with known systemic osteoporosis, the Z-scores were lower bilaterally with smaller side-to-side differences than in those with CRPS (P < 0.05). Compared with subjects suffering from long-term CRPS (≥2.4 years), patients with shorter disease duration exhibited significantly lower Z-scores (P < 0.05). In conclusion, UBD revealed that CRPS is associated with both local and systemic alterations of bone metabolism.
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The chronic pain syndrome inherited erythromelalgia (IEM) is attributed to mutations in the voltage-gated sodium channel (NaV) 1.7. Still, recent studies targeting NaV1.7 in clinical trials have provided conflicting results. Here, we differentiated induced pluripotent stem cells from IEM patients with the NaV1.7/I848T mutation into sensory nociceptors. ⋯ The IEM mutation induced a hyperpolarizing shift of NaV activation, which leads to activation of NaV1.7 at more negative potentials. Our results indicate that NaV1.7 is not active during subthreshold depolarizations, but that its activity defines the action potential threshold and contributes significantly to the action potential upstroke. Thus, our model system with induced pluripotent stem cell-derived sensory neurons provides a new rationale for NaV1.7 function and promises to be valuable as a translational tool to profile and develop more efficacious clinical analgesics.
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Back pain (BP) is a common condition of major social importance and poorly understood pathogenesis. Combining data from the UK Biobank and CHARGE consortium cohorts allowed us to perform a very large genome-wide association study (total N = 509,070) and examine the genetic correlation and pleiotropy between BP and its clinical and psychosocial risk factors. We identified and replicated 3 BP-associated loci, including one novel region implicating SPOCK2/CHST3 genes. ⋯ These findings corroborate with the current biopsychosocial model as a paradigm for BP. Overall, the results demonstrate BP to have an extremely complex genetic architecture that overlaps with the genetic predisposition to its biopsychosocial risk factors. The work sheds light on pathways of relevance in the prevention and management of low BP.