In conclusion, the actions of MG through TRPA1 activation on predominantly mechano-insensitive C fibers might be involved in spontaneously perceived pain in diabetic neuropathy and hyperalgesia as well as allodynia.
PERSPECTIVE: This study demonstrates that the activation of Cavα2δ1 and the downstream PKC-TRPA1/GJ signaling pathway contributes greatly to trigeminal nerve injury-induced secondary mechanical and cold hyperalgesia.
The observation that the TRPA1 irritant cinnamaldehyde induced heat hyperalgesia at an effect sizes comparable with that of capsaicin attributes TRPA1 a role in human heat-induced pain.
Accumulating evidences indicates that antagonists of TRPA1 and TRPM8 may protect against cisplatin, oxaliplatin, and paclitaxel-induced mitochondrial oxidative stress, inflammation, cold allodynia, and hyperalgesia.
These findings support a critical involvement of TRPA1 channels in the pathophysiology of migraine, and show their active role in counteracting hyperalgesia at the trigeminal level.
The prevention of this hyperalgesia by diclofenac (1-10μg), the inhibitors of COX-1 SC-560 (0.1-1μg) or COX-2 celecoxib (1-5μg), the TRPV1 antagonist capsazepine (0.03-0.3μg) or the TRPA1 antagonist HC030031 (10-50μg) demonstrates the involvement of prostaglandin synthesis and TRP sensitization in CCL5-evoked hyperalgesia.
Antagonism of the transient receptor potential ankyrin 1 (TRPA1) attenuates hyperalgesia and urinary bladder overactivity in cyclophosphamide-induced haemorrhagic cystitis.
Because TRPV1 and TRPA1 channels play important roles in controlling hyperalgesia in inflammatory pain models, we investigated their modulation by WIN and AM1241.
Data in our study provided evidence that pain upon injection of clinical aqueous etomidate formulations is not an unspecific effect of hyperosmolarity but rather due to a specific action mediated by activated nociceptive TRPA1 and TRPV1 ion channels in sensory neurons.
TRPA1 channels expressed in the central nervous system (CNS) have a critical role in the modulation of cortical spreading depression (CSD), which is a key pathophysiological basis of migraine pain.
Molecular docking and site-directed mutagenesis analyses suggested that saikosaponins bind to the hydrophobic pocket in TRPA1 near the Asn855 residue, which, when mutated to Ser, was previously associated with enhanced pain perception in humans.