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Steroidal and non-steroidal third-generation aromatase inhibitors induce pain-like symptoms via TRPA1

Camilla Fusi1, Serena Materazzi1, Silvia Benemei1

  • 1Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Florence 50139, Italy.

Nature Communications
|December 9, 2014
PubMed

Insights

Aromatase inhibitors (AIs) used in breast cancer therapy cause pain by activating the TRPA1 channel. Blocking this channel may treat AI-induced pain and inflammation.

Area of Science:

  • Pain research
  • Oncology
  • Neuroscience

Background:

  • Aromatase inhibitors (AIs) are crucial for breast cancer treatment.
  • Severe pain is a common side effect of AIs, but its mechanism is unclear.
  • The TRPA1 channel is implicated in pain and inflammation.

Purpose of the Study:

  • To investigate the mechanism underlying AI-induced pain.
  • To determine if AIs target the TRPA1 channel.
  • To explore TRPA1 antagonists as a potential treatment for AI-associated pain.

Main Methods:

  • Electrophysiological recordings in rodent nociceptors and human cells.
  • In vivo studies in mice, including behavioral assays and assessment of neurogenic inflammation.
  • Pharmacological blockade and genetic deletion of the TRPA1 channel.

Main Results:

  • AIs activate TRPA1 channels, leading to calcium responses and currents.
  • AIs induce acute nociception, neurogenic inflammation, mechanical allodynia, and decreased grip strength in mice.
  • These effects are significantly reduced in TRPA1-deficient mice and by TRPA1 blockade.

Conclusions:

  • TRPA1 channel activation is a key mechanism for AI-induced pain and inflammation.
  • TRPA1 plays a major role in the pro-inflammatory and pro-algesic effects of AIs.
  • TRPA1 antagonists represent a promising therapeutic strategy for managing AI-associated pain.

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