Abstract
Background: Pain and itch are unpleasant sensations specifying actual or potential tissue damage. Pain is a necessary alert signal that sets off protective responses, while itch mainly provokes the desire to scratch. Painful or itching stimulation applied to the peripheral receptors evokes a cascade of nociceptive signaling in ascending somatosensory pathways. Transient receptor potential (TRPA1 and TRPV1) channels are involved in pain and itch sensations, making them attractive targets for therapeutics.
Aims: We aimed to investigate pungent nociceptive substances, cinnamon aldehyde (CA), allyl isothiocyanate (AITC, the main compound of mustard oil), and capsaicin (CAPS) from chili peppers, which elicit thermal hyperalgesia and mechanical allodynia in mice, and studied the potential roles of TRP channels in pain modulation.
Methods: We measured nociceptive thermal paw withdrawal latencies (Hargreaves test) and mechanical thresholds (electronic von Frey test) bilaterally in mice at various time points following intraplantar applications of AITC, CA, and CAPS, which produced thermal hyperalgesia and mechanical allodynia.
Results: When pretreated with the TRPA1 antagonist (HC-030031), we found a significant reduction of these pain behavior responses to AITC and CA applications. Pretreatment with the TRPV1 antagonist (capsazepine) produced significant attenuation of thermal hyperalgesia and mechanical allodynia evoked by two doses of CAPS. We thus showed that noxious chemical irritants eliciting thermal hyperalgesia and mechanical allodynia are mediated via the activation of TRPA1 and TRPV1 cation channels.
Conclusion: The discovery of TRP channel antagonists, particularly dual antagonists that simultaneously target both TRPA1/TRPV1 channels, represents a new and promising therapeutic approach for pain treatment.