Author response: Characterization of small fiber pathology in a mouse model of Fabry disease

Hofmann, Lukas; Hose, Dorothea; Grießhammer, Anne; Blum, Robert; Döring, Frank; Dib‐Hajj, Sulayman D.; Waxman, Stephen G.; Sommer, Claudia; Wischmeyer, Erhard; Üçeyler, Nurcan

doi:10.7554/elife.39300.014

Cited by 1 publication

(8 citation statements)

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“…Tetrodotoxin-sensitive Na V currents decreased in GLAko DRGs, with a decrease in conductance that could contribute to the hyposensitivity in mice and FD patients to noxious stimuli 17 Consistent with this finding, Hofmann et al determined a reduction of Na V 1.7 currents in aged GLAko mice, as well as HEK cells in which a-Gal A had been silenced. 6 In addition, they show an increase in Na V 1.8 protein levels in younger GLAko mice.…”

Section: Ion Channels and Pain In Fdmentioning

confidence: 96%

“…4 Decreased or absent activity of a-Gal A leads to the accumulation of glycosphingolipids, mainly globotriaosylceramide (Gb3), in lysosomes of various cell types: endothelial and vascular smooth muscle cells, cardiomyocytes, kidney cells 5 and sensory and autonomic ganglia of the peripheral nervous system. 6,7 In addition, the deacylated form of Gb3, globotriaosylsphingosine (LysoGb3), is dramatically increased in plasma of "classically" affected male Fabry patients and plasma and tissues of Fabry mice. 8 Also, gender differences have been referred to in relation to pain in FD, and while the traditional view assumed females as carriers (ie, asymptomatic or mildly symptomatic), a more recent position suggests that the onset of Fabry disease symptoms in females may be comparable with that of males.…”

Section: An Overview Of Fabry Diseasementioning

confidence: 99%

“…Zhu et al 75 Hofmann et al 6 Epidermis of frontal paw glabrous skin from Glako male mice TRPV1 protein levels increased.…”

Section: Lenders Et Al 54mentioning

confidence: 99%

“…Hofmann et al documented alteration of HCN2 and the sodium channel Na V 1.7, in the GLAko (C57BL/6 backcrossed) mouse compared to control animals. 6 Even though other ion channels might also be involved, this demonstrated that increased amounts of Gb3 can lead to pathological, physiological, and behavioral signs of neuropathy. 109 Neuron hyperexcitability in DRGs soma has been analyzed in relation to Na v channels.…”

Section: Ion Channels and Pain In Fdmentioning

confidence: 99%

“…92 In a rat model of bone cancer pain, pharmacological blockade of Nav1.8 alleviated mechanical allodynia and thermal hyperalgesia. 112 Both channels were analyzed in association with FD 6,100 (see Table 3). Namer et al analyzed conduction velocities (CV) of C fibers in FD patients and a mouse GLAko model.…”

Section: Ion Channels and Pain In Fdmentioning

confidence: 99%

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Ion channels and pain in Fabry disease

et al. 2021

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Fabry disease (FD) is a progressive, X-linked inherited disorder of glycosphingolipid metabolism due to deficient or absent lysosomal α-galactosidase A (α-Gal A) activity which results in progressive accumulation of globotriaosylceramide (Gb3) and related metabolites. One prominent feature of Fabry disease is neuropathic pain. Accumulation of Gb3 has been documented in dorsal root ganglia (DRG) as well as other neurons, and has lately been associated with the mechanism of pain though the pathophysiology is still unclear. Small fiber (SF) neuropathy in FD differs from other entities in several aspects related to the perception of pain, alteration of fibers as well as drug therapies used in the practice with patients, with therapies far from satisfying. In order to develop better treatments, more information on the underlying mechanisms of pain is needed. Research in neuropathy has gained momentum from the development of preclinical models where different aspects of pain can be modelled and further analyzed. This review aims at describing the different in vitro and FD animal models that have been used so far, as well as some of the insights gained from their use. We focus especially in recent findings associated with ion channel alterations -that apart from the vascular alterations-, could provide targets for improved therapies in pain.

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Section: Ion Channels and Pain In Fdmentioning

confidence: 96%