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Targeting TRPA1 antagonists for nociplastic pain: systematic review and meta-analysis of preclinical evidence

Caren Antoniazzi1, Helen Alves Brito1, Patrícia Rodrigues1

  • 1Graduate Program in Biological Sciences: Pharmacology, Federal University of Santa Maria (UFSM), Santa Maria, RS, 97105-900, Brazil.

European Journal of Pharmacology
|August 1, 2026
PubMed

Insights

Transient receptor potential ankyrin 1 (TRPA1) antagonists effectively reduce pain hypersensitivity in preclinical models of nociplastic pain. This review supports TRPA1 as a promising therapeutic target for difficult-to-treat pain conditions.

Area of Science:

  • Neuroscience and Pharmacology
  • Pain Research and Therapeutics

Background:

  • Nociplastic pain, characterized by altered pain processing without tissue damage, presents significant treatment challenges.
  • Limited biomarkers and poor response to conventional analgesics necessitate novel therapeutic targets.
  • Transient receptor potential ankyrin 1 (TRPA1) channels are implicated in pain hypersensitivity and neuroinflammation.

Purpose of the Study:

  • To systematically review and meta-analyze preclinical evidence on the efficacy of TRPA1 antagonists in modulating nociplastic pain.
  • To evaluate the therapeutic potential of TRPA1 antagonism for conditions like migraine, chronic post-ischemia pain (CPIP), and fibromyalgia.

Main Methods:

  • Systematic literature search of PubMed, Scopus, and Web of Science (2011-2024).
  • Inclusion of 12 in vivo rodent studies evaluating TRPA1 antagonists in relevant nociplastic pain models.
  • Meta-analysis using a random-effects model to assess antinociceptive effects, primarily mechanical allodynia.

Main Results:

  • TRPA1 antagonists demonstrated consistent antinociceptive effects across various nociplastic pain models.
  • Significant reductions in mechanical and cold allodynia were observed, with high-quality evidence for CPIP and migraine models.
  • Efficacy was consistent across different doses, administration routes, and types of TRPA1 antagonists.

Conclusions:

  • Preclinical data strongly support TRPA1 as a viable therapeutic target for nociplastic pain.
  • Despite methodological limitations in some studies, TRPA1 antagonists show significant promise for translational research.
  • Further investigation is warranted to translate these findings into effective clinical treatments for chronic pain.
Keywords:
A-967079CPIPFibromyalgiaHC-030031Migraine

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