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Epiregulin and EGFR interactions are involved in pain processing
Loren J Martin1,2, Shad B Smith3, Arkady Khoutorsky4
1Department of Psychology and Alan Edwards Centre for Research on Pain, McGill University, Montreal, Quebec, Canada.
The Journal of Clinical Investigation
|August 8, 2017
Summary
Inhibiting the Epidermal Growth Factor Receptor (EGFR) with available drugs significantly reduced pain behaviors in mice. The ligand epiregulin (EREG) activates EGFR, contributing to pain via specific molecular pathways and genetic links to chronic pain.
Area of Science:
- Molecular Biology
- Neuroscience
- Pharmacology
Background:
- The Epidermal Growth Factor Receptor (EGFR) is a key member of the ErbB receptor tyrosine kinase family.
- EGFR signaling pathways are crucial for normal cellular functions like growth, proliferation, and tissue repair.
- The role of EGFR in pain processing, particularly in chronic pain conditions, remains an area of active investigation.
Purpose of the Study:
- To investigate the role of EGFR and its ligand epiregulin (EREG) in pain processing.
- To evaluate the efficacy of EGFR inhibition in preclinical models of pain.
- To elucidate the molecular mechanisms underlying EREG-mediated nociception and explore genetic associations with chronic pain.
Main Methods:
- Utilized mouse models of inflammatory and chronic pain to assess nocifensive behavior.
- Administered clinically available EGFR inhibitors to evaluate their effect on pain.
- Investigated the involvement of the PI3K/AKT/mTOR pathway and matrix metalloproteinase-9 (MMP-9) in EREG-induced nociception.
- Examined the potentiation of capsaicin-induced calcium influx in sensory neurons by EREG.
- Performed genetic association studies in clinical cohorts of temporomandibular disorder (TMD).
Main Results:
- Inhibition of EGFR with clinically available compounds significantly reduced nocifensive behavior in mouse models of inflammatory and chronic pain.
- EREG-mediated activation of EGFR enhanced nociception, involving the PI3K/AKT/mTOR pathway and MMP-9.
- EREG application potentiated capsaicin-induced calcium influx in a subset of sensory neurons.
- Genetic analysis revealed associations between EGFR and EREG genes and the development of chronic pain in TMD patient cohorts.
Conclusions:
- EGFR and its ligand EREG play a significant role in pain processing.
- EGFR inhibition demonstrates therapeutic potential for managing inflammatory and chronic pain.
- The findings suggest that EGFR and EREG are viable therapeutic targets for persistent pain conditions.
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