Mustard, garlic and chilli peppers all contain components that stimulate nociceptors, triggering pain, inflammation and hypersensitivity. These molecules target TRP receptors — a family of excitatory cation channels — and identifying the specific receptors for individual molecules could help to elucidate the mechanisms that underlie nociception and how pain is sensed. Writing in Cell, Bautista and colleagues report that TRPA1 is the sole receptor of the noxious components of mustard oil and garlic, and also link this receptor with inflammatory responses to environmental toxins.
"...TRPA1 is the sole receptor of the noxious components of mustard oil and garlic..."
Until now, it was not known whether TRPA1 was the exclusive target of the irritants allyl isothiocyanate and allicin — the noxious components of mustard oil and garlic, respectively. Using live-cell calcium imaging, the authors showed that only cultured trigeminal neurons from TRPA1-deficient mice were insensitive to either of the agents. Interestingly, deletion of this sensory gene also led to behavioural changes in the mice. Application of mustard oil to the paws would be expected to elicit flinching and paw licking. However, TRPA1-deficient mice showed neither of these responses. Furthermore, the mustard-oil-treated paws of the mutant mice were less swollen and sensitive to pain than those of wild-type mice.
Activation of sensory nerve endings in the lungs by irritants triggers neurogenic inflammation, which can aggravate conditions such as asthma. Structural similarities between one such agent — acrolein — and the potent ingredients in mustard oil and garlic prompted the authors to investigate whether this compound would also activate TRPA1. Indeed, only cells expressing TRPA1 showed a strong response to acrolein. As acrolein is also a toxic by-product of the metabolism of some chemotherapeutic drugs, these findings have therapeutic implications for the treatment of disorders such as asthma and cancer.
TRPA1 is also thought to mediate other sensory processes. It has been implicated in the perception of extreme cold and sound, and the depolarization of nociceptors in response to proalgesic agents such as bradykinin, which stimulates pain-sensing neurons, leading to hypersensitivity to heat or touch. Mice lacking TRPA1 had normal hearing functions and sensitivity to cold, suggesting that TRPA1 is not involved in the initial detection of these conditions. By contrast, administration of bradykinin evoked a considerably lower response in TRPA1-deficient mice, suggesting a role for TRPA1 in nociceptor excitation.
The identification of TRPA1 as the sole receptor responsible for the response to irritants in mustard oil and garlic not only provides insights into the mechanisms that underlie pain sensation, but also has therapeutic implications. Blocking TRPA1 activity has the potential to prolong cancer therapy and alleviate the symptoms of pulmonary diseases, such as asthma.