Question: 

TRPA1 receptor channels are known to be activated by environmental irritants as well as by endogenous mediators released in inflammatory conditions. Activation of these receptors of trigeminal afferents innervating meningeal structures have recently been suggested to be involved in the generation of headaches. Therefore we investigated the role of TRPA1 in meningeal nociception in four different rat models.

Methods: 

1. The hemisected cranial preparation was used to sample fluid containing calcitonin gene-related peptide (CGRP) released from the dura mater and measured by an ELISA. 2. In a similar preparation the discharge activity of meningeal afferents innervating the cranial dura mater was recorded. 3. Meningeal blood flow was monitored in the exposed dura mater using laser Doppler flowmetry. 4. The activity of second order neurons in the spinal trigeminal nucleus with afferent input from the dura mater was recorded. In all preparations acrolein (10^-4 M) was used as a TRPA1 agonist and applied on the dura mater.

Results: 

During 5 min superfusion acrolein caused significant CGRP release and increased meningeal blood flow. Both responses were suppressed by the TRPA1 inhibitor HC030031. In contrast, acrolein did not cause discharges in meningeal Ad- or C-fibres in vitro and did not change the discharge activity of second order neurons with meningeal receptive fields.

Conclusions: 

TRPA1 channel activation causes Ca²⁺-dependent neuropeptide release in meningeal afferents but this seems not to be sufficient to generate action potentials dependent on voltage-gated sodium channels. Therefore a decisive role of TRPA1 receptor channels in headache generation appears questionable.