Dr. Maria Maiarú completes Early Career Research Grant Project

Apr 27, 2020

IASP is excited to report on the research of 2017 Early Career Research Grant recipient, Dr. Maria Maiarú. The IASP Early Career Research Grant facilitates the development of young researchers just starting their careers as independent investigators. 

IASP: Can you give us a summary of your project? What were your conclusions?

Maiarú: With the Early Career Research Grant I was able to demonstrate that autophagy is engaged in the spinal cord of mice in different models of chronic pain. Specifically, I found that pain models have different effects on the activation of the autophagic pathway; that autophagy is differently activated between FKBP5 KO and WT mice in a naïve state; that autophagy is promoted in FKBP5 KO mice starting at 5 days after SNI surgery; and that, using a model of chemotherapy-induced neuropathy, autophagy is upregulated in the spinal cord of FKBP5 KO mice compared to WT. Overall, our data suggest that in persistent pain states induced by damage to peripheral nerves following SNI surgery or Paclitaxel injection, global deletion of FKBP5 prevents the nerve injury-induced impairment of autophagy in the spinal cord and this is associated with a reduced development of hypersensitivity.

What exactly is autophagy?

Autophagy is a physiological mechanism in the cell that contributes to protein and organelle degradation, cellular remodelling and survival. Breaking down the roots of the word, "auto” means self and “phagy” means eat. Autophagy literally means "self-eating." Basically, autophagy is the body's way of cleaning out damaged cells, in order to regenerate newer, healthier cells.

Did your research support your hypothesis? 

Yes! The results of this project support my hypothesis that a different modulation of autophagy between FKBP51 KO and WT mice could be one of the mechanisms underlying the difference in the development of mechanical hypersensitivity observed between the two genotypes.

This graphical abstract (below) is a model of FKBP5’s role in directing autophagy in chronic pain states due to nerve injury. Increased induction of autophagy induced by FKBP51 induces impairment of autophagosome’s clearance after nerve injury resulting in a state of hypersensitivity. Knocking down FKBP5 prevents the accumulation of autophagosomes, resulting in a reduced pain sensitivity after nerve injury.

Have you been able to present these results anywhere or form any collaborations? 

Thanks to the data collected with this grant I started two international collaborations with institutions in Italy, and I have been recently awarded a research grant to further expand my research. I presented the data at the 2019 NeupSIG Meeting in London and am currently writing a research paper to be submitted for publication shortly.

Has the grant allowed you to learn anything outside of the specific research findings?

I think this grant was really important in that it also allowed me to manage the grant and plan the experimental which are useful learning outcomes for my future career. 

How will this research impact your future career? 

The IASP Early Career Research Grant has given me the opportunity to carry out important preclinical research to test the potential of targeting FKBP51 and the autophagic pathway for pain relief. There is evidence for the role of autophagy in the development and maintenance of neuropathic pain, but very little is known about its involvement in the pathogenesis of chronic-inflammatory pain. The successful results obtained with this project are encouraging me to further investigate whether autophagy is a critical event in the development and maintenance of chronic pain.

I highly recommend this scheme to all the young scientists who wish to start their own line or research. This grant has helped me to start my career as an independent research and I have been recently appointed as Lecturer at the University of Reading, where I will continue my research on autophagy and pain. I highly recommend this scheme to all the young scientists who wish to start their own line or research.