Increased expression of trpv1 in peripheral terminals mediates thermal nociception in fabry disease mouse model

Jarmila Lakomà, Roberto Rimondini, Antonio Ferrer Montiel, Vincenzo Donadio, Rocco Liguori, Marco Caprini

Research output: Contribution to journalArticlepeer-review


Fabry disease is a X-linked lysosomal storage disorder caused by deficient function of the alpha-galactosidase A (α-GalA) enzyme. α-GalA deficiency leads to multisystemic clinical manifestations caused by the preferential accumulation of globotriaosylceramide (Gb3) in the endothelium and vascular smooth muscles. A hallmark symptom of Fabry disease patients is neuropathic pain that appears in the early stage of the disease as a result of peripheral small fiber damage. The α-GalA gene null mouse model (α-GalA(-/0)) has provided molecular evidence for the molecular alterations in small type-C nociceptors in Fabry disease that may underlie their hyperexcitability, although the specific mechanism remains elusive. Here, we have addressed this question and report that small type-C nociceptors from α-GalA(-/0) mice exhibit a significant increase in the expression and function of the TRPV1 channel, a thermoTRP channel implicated in painful heat sensation. Notably, male α-GalA(-/0) mice displayed a ≈ 2-fold higher heat sensitivity than wild-type animals, consistent with the augmented expression levels and activity of TRPV1 in α-GalA(-/0) nociceptors. Intriguingly, blockade of neuronal exocytosis with peptide DD04107, a process that inhibits among others the algesic membrane recruitment of TRPV1 channels in peptidergic nociceptors, virtually eliminated the enhanced heat nociception of α-GalA(-/0) mice. Together, these findings suggest that the augmented expression of TRPV1 in α-GalA(-/0) nociceptors may underly at least in part their increased heat sensitivity, and imply that blockade of peripheral neuronal exocytosis may be a valuable pharmacological strategy to reduce pain in Fabry disease patients, increasing their quality of life.

Original languageEnglish
Pages (from-to)1-16
Number of pages16
JournalMolecular Pain
Publication statusPublished - Jan 1 2016


  • Fabry disease
  • Ion channels
  • Pain
  • Small fiber neuropathy
  • α-GalA null mice

ASJC Scopus subject areas

  • Molecular Medicine
  • Cellular and Molecular Neuroscience
  • Anesthesiology and Pain Medicine


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