The formalin test does not probe inflammatory pain but excitotoxicity in rodent skin.
TRPA1
analgesia
formaldehyde
nociception
toxicokinetics
Journal
Physiological reports
ISSN: 2051-817X
Titre abrégé: Physiol Rep
Pays: United States
ID NLM: 101607800
Informations de publication
Date de publication:
03 2022
03 2022
Historique:
revised:
19
01
2022
received:
03
09
2021
accepted:
24
01
2022
entrez:
27
3
2022
pubmed:
28
3
2022
medline:
5
4
2022
Statut:
ppublish
Résumé
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
Identifiants
pubmed: 35340127
doi: 10.14814/phy2.15194
pmc: PMC8957662
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e15194Informations de copyright
© 2022 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.
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