Rapid translation from bench to bedside of topical menthol, a TRPM8 agonist, for management of peripheral neuropathic pain, using an RCT with fMRI

Each year in Scotland 16,000 patients receive potentially neurotoxic chemotherapy. 90% of these develop chemotherapy-induced peripheral neuropathy (CIPN); severe peripheral pain and abnormal sensation. This can limit chemotherapy treatment and impact on survival. CIPN can continue for over a year after chemotherapy in 50% of patients, there are no proven effective treatments and the drugs used currently have side-effects often described as worse than the neuropathy itself. Our group of scientists and doctors have been working on development of a simple, non toxic but effective gel (menthol) applied to the skin to manage CIPN. We have published our highly promising findings with menthol in patients with CIPN, however, to formally prove the treatment’s value, we now need to do a randomised controlled trial where 50% of patients receive a placebo (inactive) gel twice daily, and the other 50%, menthol (with neither patients nor doctors knowing which until after the study). As well as measuring the patient’s pain scores we will use state-of-the-art brain imaging to understand changes in the brain pain pathways during pain relief. This will give us new knowledge on how the treatment works and provide the formal evidence needed before it can be made widely available to many patients.