Cooling a burning mouth: is TRPM8 the therapeutically relevant target of clonazepam in burning mouth disorder?

Burning mouth disorder (BMD) is an extremely painful oral condition that occurs at the highest prevalence in post-menopausal women. Treatment options remain limited and remission rates poor, highlighting a need for identification of relevant molecular targets that can be prosecuted for effective therapeutics. One treatment that realizes benefit in patients with burning mouth disorder is clonazepam, a benzodiazepine known to work by augmenting currents through gamma aminobutyric acid A (GABAA) ion channels to inhibit neuronal firing. Here, we highlight an ancillary target for clonazepam as the transient receptor potential melastatin 8 (TRPM8) ion channel. In this commentary, evidence supporting the idea that TRPM8 acts as the therapeutically relevant local mediator of clonazepam action in BMD is summarized, with the goal of spurring new treatments for this debilitating and painful condition.