Background: Mutations in the voltage-gated Na(V)1.7 Na+ channel alpha 1 gene SCN9A have been linked to pain disorders, such as inherited primary erythromelalgia and paroxysmal extreme pain disorder... Show moreBackground: Mutations in the voltage-gated Na(V)1.7 Na+ channel alpha 1 gene SCN9A have been linked to pain disorders, such as inherited primary erythromelalgia and paroxysmal extreme pain disorder. Both show clinical overlap with complex regional pain syndrome (CRPS), a condition that is characterized by pain in association with combinations of vasomotor, sudomotor, sensory, and motor disturbances. Therefore, we here investigated the involvement of the SCN9A gene in familial CRPS. Methods: We performed a mutation analysis of the SCN9A gene in four index cases of families with CRPS. All 26 coding exons and adjacent sequences of the SCN9A gene were analyzed for mutations using direct sequencing analysis. Results: No causal gene mutations were identified in the SCN9A gene in any of the patients. Conclusions: Despite the fact that the SCN9A gene is an excellent candidate, we did not find evidence that it plays a major role in familial CRPS. Show less
Gosso, M.F.; Rooij, A.M. de; Alsina-Sanchis, E.; Kamphorst, J.T.; Marinus, J.; Hilten, J.J. van; Maagdenberg, A.M.J.M. van den 2010
Complex regional pain syndrome type 1 (CRPS-1) is a chronic pain disorder that in some patients is associated with fixed dystonia. The pathogenesis of CRPS and its relation to dystonia remain... Show moreComplex regional pain syndrome type 1 (CRPS-1) is a chronic pain disorder that in some patients is associated with fixed dystonia. The pathogenesis of CRPS and its relation to dystonia remain poorly understood. Several genes (so-called DYT genes) identified in other causes of dystonia play a role in mechanisms that have been implicated in CRPS. Because different mutations in the same gene can result in diverse phenotypes, we sequenced all coding exons of the DYT1, DYT5a, DYT5b, DYT6, DYT11, DYT12, and DYT16 genes in 44 CRPS patients with fixed dystonia to investigate whether high-penetrant causal mutations play a role in CRPS. No such mutations were identified, indicating that these genes do not seem to play a major role in CRPS. Show less
Huehne, K.; Schaal, U.; Leis, S.; Uebe, S.; Gosso, M.F.; Maagdenberg, A.M.J.M. van den; ... ; Winterpacht, A. 2010
Complex regional pain syndrome (CRPS) is a condition that is characterized by severe pain and exaggerated neurogenic inflammation, which may develop after injury or surgery. Neurogenic inflammation... Show moreComplex regional pain syndrome (CRPS) is a condition that is characterized by severe pain and exaggerated neurogenic inflammation, which may develop after injury or surgery. Neurogenic inflammation is mediated by neuropeptides, such as calcitonin gene-related peptide (CGRP) and substance P (SP) that are released from nociceptors. Genetic factors may play a role in CRPS as was suggested by the occurrence of familial cases and several genetic association studies investigating mainly the human leukocyte antigen (HLA) system. Here we investigated the role of neutral endopeptidase (NEP), a key enzyme in neuropeptide catabolism. NEP dysfunction resulting in reduced inactivation of neuropeptides may be a possible pathomechanism in CRPS. To this end, we tested a GT-repeat polymorphism, in the NEP promoter region as well as 18 tag-SNPs in six linkage disequilibrium (LD) blocks in the NEP gene region in 320 CRPS patients and 376 controls. No significant genetic association was observed. Thus, we conclude that the NEP gene does not seem to be a major risk factor for CRPS. (C) 2010 Elsevier Ireland Ltd. All rights reserved. Show less
