Insight neuropathic pain in Fabry disease:prokineticin system and neuroinflammation as novel therapeutic targets

Pain accompanies Fabry patients during all life. Analgesics are not fully effective, and specific therapies, such as ERT and migalastat, do not successfully relieve pain that  is often related to mood alterations. Besides, stressful events like physical activity can trigger unbearable pain crises especially in paediatric patients who refrain from socializing, for fear of triggering a crisis. In previous work, we started to look for novel treatments for pain and demonstrated in a FD-mouse model, that the antibiotic minocycline and a drug that blocks a molecule called prokineticin are effective in relieving pain.

This project wants to continue the research, considering aspects that may help to translate it to clinic. We want to investigate in the FD-mouse the effect of the combination of the novel analgesic treatments, that we demonstrated effective in pain relief, with ERT. Since physical activity often triggers pain crisis, we will set up in FD-mouse a protocol of physical exercise capable of mimicking  the pain crisis to understand the mechanisms and impact on mood. The effect of our treatments on pain crisis will be assessed to promote a strategy to prevent them and impact on wellbeing. Cultures of different types of cells that are involved in pain generation will be used to better understand the mechanisms at the basis of pain in FD. To achieve these results the most  appropriate and advanced techniques will be applied. In conclusion this study will lead to new and better treatments for pain and related psychic alterations in FD.