| First Author | Lakomá J | Year | 2014 |
| Journal | PLoS One | Volume | 9 |
| Issue | 10 | Pages | e108641 |
| PubMed ID | 25337704 | Mgi Jnum | J:223547 |
| Mgi Id | MGI:5649486 | Doi | 10.1371/journal.pone.0108641 |
| Citation | Lakoma J, et al. (2014) Pain related channels are differentially expressed in neuronal and non-neuronal cells of glabrous skin of fabry knockout male mice. PLoS One 9(10):e108641 |
| abstractText | Fabry disease (FD) is one of the X-linked lysosomal storage disorders caused by deficient functioning of the alpha-galactosidase A (alpha-GalA) enzyme. The alpha-GalA deficiency leads to multi-systemic clinical manifestations caused by the preferential accumulation of globotriaosylceramide in the endothelium and vascular smooth muscles. A hallmark symptom of FD patients is peripheral pain that appears in the early stage of the disease. Pain in FD patients is a peripheral small-fiber idiopathic neuropathy, with intra-epidermal fiber density and integrity being used for diagnosing FD in humans. However, the molecular correlates underlying pain sensation in FD remain elusive. Here, we have employed the alpha-GalA gene KO mouse as a model of FD in rodents to investigate molecular changes in their peripheral nervous system that may account for their algesic symptoms. The alpha-GalA null mice display neuropathic pain as evidenced by thermal hyperalgesia and mechanical allodynia, with histological analyses showing alterations in cutaneous innervation. Additionally, KO mice showed a decreased and scattered pattern of neuronal terminations consistent with the reduction in neuronal terminations in skin biopsies of patients with small fiber neuropathies. At the molecular level KO animals showed an increase in the expression of TRPV1 and Nav1.8, and a decrease in the expression of TRPM8. Notably, these alterations are observed in young animals. Taken together, our findings imply that the alpha-GalA KO mouse is a good model in which to study the peripheral small fiber neuropathy exhibited by FD patients, and provides molecular evidence for a hyperexcitability of small nociceptors in FD. |
