Chemotherapy-induced peripheral neuropathy (CIPN) occurs in up to 70% of patients receiving chemotherapy for cancer. Safe, effective analgesia for CIPN patients is an important unmet need. Assessment of new analgesics by randomised controlled trials (RCTs) is complicated by the subjective nature of pain and the influence of an active placebo response, resulting in analgesic RCTs often describing small effect sizes, which are difficult to interpret clinically. Specifically in CIPN, the varied individual experiences of neuropathic pain, not easy to standardise clinically or with Quantitative Sensory Testing (QST), make the assessment of new analgesics particularly difficult.
The advent of fMRI as a research tool, with its ability to detect alterations in regional CNS activity underpinning behavioural changes, has greatly aided in unravelling processes of plasticity in the CNS. In our earlier preclinical work we discovered that peripheral activation of non-nociceptive afferents, which express the TRPM8 ion channel (and normally participate in sensing innocuous cool temperatures) results in central suppression of hypersensitive neuropathic pain. The mechanism appears to involve non-opioid gating within the spinal dorsal horn, but how this impacts on supraspinal pain processing is unknown. Our group and others have provided case study and proof-of-concept open label trial data establishing the clinical efficacy of this strategy in neuropathic pain patients. Evolving this evidence is now very important clinically. Our RCT of topical menthol vs placebo for CIPN, with embedded fMRI should enhance the evidence base significantly. The study will provide important new opportunities to assess alignment between clinical, QST and fMRI evaluation of the efficacy of TRPM8 agonist treatment and further, gain insights into functional (and connectivity) changes in forebrain regions registering affective, as well as sensory-discriminitive pain responses.
For details of this project with Prof Marie Fallon, Dr Heather Whalley, Prof Susan Fleetwood-Walker and Dr Paul Mitchell at the University of Edinburgh, go to https://www.findaphd.com/search/ProjectDetails.aspx?PJID=98990
The deadline for application is 7 August 2018