Please confirm that an ethics committee approval has been applied for or granted: Not relevant (see information at the bottom of this page)
Background and Aims Fabry disease is an X-linked disorder caused by mutations in the GLA gene, leading to globotriaosylceramide (Gb3) accumulation on the lysosome. Patients experience numerous forms of pain, including evoked and chronic pain. The exact cause of the pain has yet to be entirely understood. Still, the peripheral nervous system, cardiac, renal, sensory, and autonomic ganglion cells are particularly affected by the deposits of Gb3.
Methods A bioinformatic analysis of likely genes related to and signaling pathways involved in the manifestation of pain in Fabry disease was performed. A literature review on possible physiopathogenesis of pain mechanisms was also carried out.
Results In the bioinformatic analysis, we identified through the DisGeNET database around 207 genes related to chronic pain, 266 genes in inflammatory pain, and 24 genes in peripheral neuropathic pain. The Venny 2.1 online platform was used to find common genes between these pathologies, identifying around 78 common genes. An interaction network was built on the STRING platform for these 78 genes. The pathways discovered through this analysis include inflammatory mediator regulation of TRP channels, the VEGF pathway, neuroinflammation, and the relationship between COX2 and EGFR. Among the principal explanations for the physiopathogenesis in the literature, the accumulation of Gb3 in the sacral plexus, the activation of the Notch 1 pathway, and the function of ion channels (KCa3.1 channels) are involved in the mechanism of initiation.
Conclusions This analysis aims to explain unresolved key pathophysiologic features of pain without discarding the possibility of additional genomics factors and providing future investigation opportunities.