ArticlePhysiological reports2022
The formalin test does not probe inflammatory pain but excitotoxicity in rodent skin.
Article in Physiological reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 32 citations in OpenAlex.
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- Effects of a novel acetaminophen analog on cardiorespiratory compensatory responses and survival in a male rat model of traumatic hemorrhage.Physiological reports · 2025Article
- Mitogen- and stress-activated kinase 1 in primary sensory neurons contributes to formalin-induced tonic pain.Pain reports · 2025Article
- Volatilome and Antinociceptive Activity of the Traditional Preparation and Compounds from Ageratina grandifolia (Regel) R.M. King & H. Rob.Chemistry & biodiversity · 2025Article
- Preclinical Animal Models to Investigate the Role of NaLife (Basel, Switzerland) · 2025Review
- The analgesic and anti-inflammatory effects of a combined preparation based on the blunt-nosed viper's venom and oregano essential oil.The Korean journal of pain · 2025Article
- Pharmacological Evaluation of Novel Hydrazide and Hydrazone Derivatives: Anti-Inflammatory and Analgesic Potential in Preclinical Models.Molecules (Basel, Switzerland) · 2025Article
- Discordance between preclinical and clinical testing of Na V 1.7-selective inhibitors for pain.Pain · 2025Review
- Advancing Pain Understanding and Drug Discovery: Insights from Preclinical Models and Recent Research Findings.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Antinociceptive Behavior, Glutamine/Glutamate, and Neopterin in Early-Stage Streptozotocin-Induced Diabetic Neuropathy in Liraglutide-Treated Mice under a Standard or Enriched Environment.International journal of molecular sciences · 2024Article
- Low-Frequency Stimulation of Trpv1-Lineage Peripheral Afferents Potentiates the Excitability of Spino-Periaqueductal Gray Projection Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Topical Oxaliplatin Produces Gain- and Loss-of-Function in Multiple Classes of Sensory Afferents.The journal of pain · 2024Article
- Unraveling the parameters and biological mechanisms of COFrontiers in neurology · 2023Article
- The formalin test does not probe inflammatory pain but excitotoxicity in rodent skin.Physiological reports · 2022Article
- Pregabalin attenuates long-lasting post-inflammatory nociplastic mechanical sensitization in mice.Neurobiology of pain (Cambridge, Mass.)Article
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The most widely used formalin test to screen antinociceptive drug candidates is still apostrophized as targeting inflammatory pain, in spite of strong opposing evidence published. In our rat skin-nerve preparation ex vivo, recording from all classes of sensory single-fibers (n = 32), 30 units were transiently excited by formaldehyde concentrations 1-100 mM applied to receptive fields (RFs) for 3 min, C and Aδ-fibers being more sensitive (1-30 mM) than Aβ-fibers. From 30 mM on, ~1% of the concentration usually injected in vivo, all RFs were defunctionalized and conduction in an isolated sciatic nerve preparation was irreversibly blocked. Thus, formaldehyde, generated a state of 'anesthesia dolorosa' in the RFs in so far as after a quiescent interphase all fibers with unmyelinated terminals developed a second phase of vigorous discharge activity which correlated well in time course and magnitude with published pain-related behaviors. Sural nerve filament recordings in vivo confirmed that higher formalin concentrations (> 42 mM) have to be injected to the skin to induce this second phase of discharge. Patch-clamp and calcium-imaging confirmed TRPA1 as the primary transducer of formaldehyde (10 mM) effects on mouse sensory neurons. However, stimulated CGRP release from isolated skin of TRPA1
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