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Role of transient receptor potential ankyrin 1 receptors in rodent models of meningeal nociception – Experiments in vitro
Author(s) -
Denner A.C.,
Vogler B.,
Messlinger K.,
De Col R.
Publication year - 2017
Publication title -
european journal of pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.305
H-Index - 109
eISSN - 1532-2149
pISSN - 1090-3801
DOI - 10.1002/ejp.986
Subject(s) - trpv1 , transient receptor potential channel , calcitonin gene related peptide , chemistry , nociception , receptor , acrolein , pharmacology , nociceptor , trigeminal ganglion , neurogenic inflammation , medicine , endocrinology , neuroscience , biochemistry , neuropeptide , sensory system , biology , substance p , catalysis
Background The TRP channel ankyrin type 1 ( TRPA 1) is a nonselective cation channel known to be activated by environmental irritants, cold and endogenous mediators of inflammation. Activation of TRPA 1 in trigeminal afferents innervating meningeal structures has recently been suggested to be involved in the generation of headaches. Methods Two in vitro models of meningeal nociception were employed using the hemisected rodent head preparation, (1) recording of single meningeal afferents and (2) release of calcitonin gene‐related peptide ( CGRP ) from the cranial dura mater. The role of TRPA 1 was examined using the TRPA 1 agonists acrolein and mustard oil ( MO ). BCTC , an inhibitor of TRP vanilloid type 1 receptor channels ( TRPV 1), and the TRPA 1 inhibitor HC 030031 as well as mice with genetically deleted TRPA 1 and TRPV 1 proteins, were used to differentiate between effects. Results Acrolein did not cause discharge activity in meningeal Aδ‐ or C‐fibres but increased the electrical activation threshold. Acrolein was also effective in releasing CGRP from the dura of TRPV 1 −/− but not of TRPA 1 −/− mice. MO increased the discharge activity of afferent fibres from rat as well as C57 wild‐type and TRPA 1 −/− but not TRPV 1 −/− mice. The effect was higher in C57 compared to TRPA 1 −/− mice. Conclusion Sole TRPA 1 receptor channel activation releases CGRP and increases the activation threshold of meningeal afferents but does not generate propagated activity, and so would be capable of causing local effects like vasodilatation but not pain generation. In contrast, combined TRPA 1 and TRPV 1 activation may be rather pronociceptive supporting headache generation. Significance Sole activation of TRPA1 receptor channels increases the activation threshold but does not cause propagated action potentials in meningeal afferents. TRPA1 agonists cause CGRP release from rodent dura mater. Peripheral TRPA1 receptors may have a pronociceptive function in trigeminal nociception only in combination with TRPV1.