RNA-binding protein MBNL2 mitigates neuropathic pain after chemotherapy through destabilizing CCR2 expression in

Keshi Yan1, Ruining Ma1, Bing Wang1

  • 1Department of Anesthesiology, New Jersey Medical School, Rutgers, The State University of New Jersey, Newark, NJ 07103, USA.

Insights

Muscleblind-like protein 2 (MBNL2) downregulation in dorsal root ganglion (DRG) neurons causes chemotherapy-induced neuropathic pain (CINP) by increasing C-C chemokine receptor type 2 (CCR2). Restoring MBNL2 alleviates CINP symptoms.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Pharmacology

Background:

  • Chemotherapy-induced neuropathic pain (CINP) arises from gene expression changes in dorsal root ganglion (DRG) neurons.
  • The precise molecular mechanisms underlying these gene expression alterations in CINP remain largely unknown.

Purpose of the Study:

  • To investigate the role of muscleblind-like protein 2 (MBNL2) in the development of paclitaxel-induced neuropathic pain.
  • To elucidate the molecular mechanisms by which MBNL2 influences gene expression in DRG neurons relevant to CINP.

Main Methods:

  • Paclitaxel injection in mice to induce neuropathic pain.
  • Analysis of MBNL2 and C-C chemokine receptor type 2 (CCR2) expression in DRG neurons.
  • Experimental manipulation of MBNL2 levels in DRG neurons.
  • Assessment of pain behaviors including mechanical allodynia and thermal hyperalgesia.

Main Results:

  • Paclitaxel treatment downregulated MBNL2 expression in DRG neurons.
  • MBNL2 downregulation led to increased CCR2 expression and CINP-like symptoms.
  • Restoring MBNL2 expression in DRG neurons mitigated paclitaxel-induced pain behaviors.
  • MBNL2 directly binds to Ccr2 mRNA, regulating its stability and subsequent CCR2 protein levels.

Conclusions:

  • MBNL2 plays a critical neuroprotective role in alleviating chemotherapy-induced neuropathic pain.
  • The MBNL2-CCR2 axis in DRG neurons represents a potential therapeutic target for managing CINP.
  • Understanding MBNL2's function offers insights into novel strategies for pain management.

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