ArticleBritish journal of pharmacology2015
The TRPA1 channel mediates the analgesic action of dipyrone and pyrazolone derivatives.
Article in British journal of pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 77 citations in OpenAlex.
- Hematological parameters in patients with chronic pain on long-term dipyrone therapy followed in a tertiary hospital: a retrospective cohort study.Clinics (Sao Paulo, Brazil) · 2026Article
- Bortezomib-induced peripheral neuropathy: from molecular mechanisms to clinical management.Frontiers in pharmacology · 2025Review
- Article
- Roles of airway and intestinal epithelia in responding to pathogens and maintaining tissue homeostasis.Frontiers in cellular and infection microbiology · 2024Review
- Functions of TRPs in retinal tissue in physiological and pathological conditions.Frontiers in molecular neuroscience · 2024Review
- Research Progress on TRPA1 in Diseases.The Journal of membrane biology · 2023Review
- TRP Channels in Cancer: Signaling Mechanisms and Translational Approaches.Biomolecules · 2023Review
- Migraine Treatment: Towards New Pharmacological Targets.International journal of molecular sciences · 2023Review
- Neuronal and non-neuronal TRPA1 as therapeutic targets for pain and headache relief.Temperature (Austin, Tex.) · 2023Review
- Powerful Potential of Polyfluoroalkyl-Containing 4-Arylhydrazinylidenepyrazol-3-ones for Pharmaceuticals.Molecules (Basel, Switzerland) · 2022Article
- Nobel somatosensations and pain.Pflugers Archiv : European journal of physiology · 2022Review
- Real world evidence of the use of metamizole (dipyrone) by the Brazilian population. A retrospective cohort with over 380,000 patients.Einstein (Sao Paulo, Brazil) · 2022Article
- Periorbital Nociception in a Progressive Multiple Sclerosis Mouse Model Is Dependent on TRPA1 Channel Activation.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Involvement of Opioid System and TRPM8/TRPA1 Channels in the Antinociceptive Effect ofBiomolecules · 2021Article
- Pathological Mechanisms of Bortezomib-Induced Peripheral Neuropathy.International journal of molecular sciences · 2021Review
- Comparative Effects of Metamizole (Dipyrone) and Naproxen on Renal Function and Prostacyclin Synthesis in Salt-Depleted Healthy Subjects - A Randomized Controlled Parallel Group Study.Frontiers in pharmacology · 2021Article
- Metamizole relieves pain by influencing cytokine levels in dorsal root ganglia in a rat model of neuropathic pain.Pharmacological reports : PR · 2020Article
- CBBritish journal of pharmacology · 2020Article
- Eslicarbazepine acetate interacts in a beneficial manner with standard and alternative analgesics to reduce trigeminal nociception.Psychopharmacology · 2020Article
- Inhibition of microRNA-155 Reduces Neuropathic Pain During Chemotherapeutic Bortezomib via Engagement of Neuroinflammation.Frontiers in oncology · 2020Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeAlthough still used by hundreds of millions of people worldwide, the mechanism of the analgesic action of the pyrazolone derivatives (PDs), dipyrone, propyphenazone and antipyrine remains unknown. The transient receptor potential ankyrin 1 (TRPA1) channel, expressed by nociceptors, is emerging as a major pain transduction pathway. We hypothesized that PDs target the TRPA1 channel and by this mechanism produce their analgesic effect. EXPERIMENTAL APPROACH: Calcium responses and currents were studied in cultured TRPA1-expressing rodent dorsal root ganglion neurons and human cells. Acute nociception and mechanical hypersensitivity were investigated in naïve and genetically manipulated mice. KEY
resultsPyrazolone and PDs selectively inhibited calcium responses and currents in TRPA1-expressing cells and acute nocifensor responses in mice evoked by reactive channel agonists (allyl isothiocyanate, acrolein and H2 O2 ). In line with recent results obtained with TRPA1 antagonists and TRPA1 gene deletion, the two most largely used PDs, dipyrone and propyphenazone, attenuated TRPA1-mediated nociception and mechanical allodynia in models of inflammatory and neuropathic pain (formalin, carrageenan, partial sciatic nerve ligation and the chemotherapeutic drug, bortezomib). Notably, dipyrone and propyphenazone attenuated carrageenan-evoked mechanical allodynia, without affecting PGE2 levels. The main metabolites of PDs did not target TRPA1 and did not affect TRPA1-dependent nociception and allodynia. CONCLUSIONS AND IMPLICATIONS: Evidence that in rodents the nociceptive/hyperalgesic effect produced by TRPA1 activation is blocked by PDs suggests that a similar pathway is attenuated by PDs in humans and that TRPA1 antagonists could be novel analgesics, devoid of the adverse haematological effects of PDs.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.