Patients will be recruited who have peripheral neuropathy due to chemotherapy. They will be given a blinded treatment of gel containing either menthol (3%) or placebo to be applied for 6 weeks, twice a day. Assessments of pain, neuropathic symptoms and impact on quality of life will be done at baseline, 6 weeks and 12 weeks. Functional magnetic resonance imaging (fMRI) scans will be done at baseline and 6 weeks. Physical activity data will also be collected to be analysed in conjunction with pain assessments.

Modern cancer treatments, while more effective at prolonging life, are associated with some long lasting effects, especially nerve pain. This occurs in up to 90% of patients and 50% of patients still experience nerve pain a year after treatment. Not only is this distressing in itself but the investigators now understand that this treatment-related pain is exacerbating other pains, making cancer pain more difficult to control. The problem with managing nerve pain caused by treatment is that there is no predictable and effective treatment.

Our team has discovered that menthol cream or gel applied to the skin in the area of nerve pain can be effective. This trial seeks to provide better evidence of using this simple, cheap, non-toxic treatment. Participants will be given either menthol gel to the affected area or a placebo gel which smells, looks like and has the same texture as menthol but has no active drug. The gel will be applied twice a day for 6 weeks.

Participants will initially be assessed for pain and its impact on function, mood and quality of life and, if possible, will also have an fMRI scan immediately before starting menthol treatment and after 6 weeks of treatment. They will also have some assessments a further 6 weeks after treatment finishes. As part of impact on function assessment, participants will be asked to wear a physical activity monitor for a few days prior to each of the three main assessment points.

Our group has used special scans of the brain called fMRI to help identify if a treatment has real potential for patients. Sometimes, in early studies of a new treatment, patients can believe that the treatment has a real effect, but in fact it is a placebo effect. FMRI scans in this study will help to identify if menthol gel is having a true pain relieving effect, by comparing the patient's reports of pain with their scan findings. This will be very helpful in aiding the decision of how the research team conduct any future larger clinical trial.

Inclusion Criteria:

1. Patients have received any neurotoxic chemotherapy.
2. Patients have experienced post treatment Chemotherapy Induced Peripheral Neuropathy (CIPN) pain for a minimum of 3 months after completing chemotherapy.
3. Patients reporting a distressing or uncomfortable neuropathic symptom (such as pain or tingling) with an average score in the last 24 hours of ≥5 on a scale of 0-10 with 0 being none, according to the Numeric Rating Scale for pain.
4. Aged 18 years or over at study entry.
5. Patient's Oncology team agrees to their taking part in the study.
6. Patients are able to provide written informed consent to participation in the study after explanation of the study protocol.
7. In the opinion of the investigator, the patient is able to complete the various assessments.
8. Neuropathy must be confined to the distal extremities (distal to elbows and/or knees).

Exclusion Criteria:

1. Pre-existing or history of peripheral neuropathy due to any cause other than chemotherapy (diabetes, alcohol, toxin, hereditary, etc.).
2. Patients with any contraindication to the use of topical therapy or menthol.
3. Neurological conditions which may influence findings (such as Multiple Sclerosis or residual signs/symptoms from a previous stroke).
4. Skin conditions which prevent assessment of the relevant areas affected by peripheral neuropathy.
5. Suffering from significant psychiatric illness, which would hinder their completion of the study in the opinion of the investigator.
6. General medical condition is unstable or rapidly deteriorating, such that they are unlikely to be able to contribute to the study.
7. In the opinion of the Research Team or their usual medical team, would be unable to complete the study protocol for any other reason.
8. Current treatment of ≤ 30 days duration with topical lidocaine patch/gel or anticonvulsants, tricyclic antidepressants, MAO inhibitor, or other neuropathic pain medication agents such as carbamazepine, phenytoin, valproic acid, gabapentin/pregabalin, lamotrigine or amifostine. (If on the same dose of any of these medications for >31 days, patients will be asked to continue these for the duration of the study. Analgesic agents such as acetaminophen, nonsteroidal anti-inflammatory agents, or opioids, are allowed if on the same doses for >31 days).
9. Application of capsaicin cream or patch (to the limb extremities) currently or within the last 30 days (as this would interfere with application of the menthol gel and potentially study outcome).
10. Patients with significant pain other than CIPN (ie pain worse than the CIPN).
11. Other medical conditions, which in the opinion of the treating physician/allied health professional would make this protocol unreasonably hazardous for the patient.
12. Participants previously randomised into this study.
13. Participants not prepared to stop using any other physical activity meter.
14. Co-enrolment in any other pain treatment studies.

Anyone interested in secondary analysis of the data should contact the Chief Investigator in the first instance.

Gel tubes will be supplied with similar labelling, identified by blinded drug pack numbers which can be linked to the treatment allocation if an emergency need arises. The menthol and placebo gels have a similar blue colour and both have a minty odour.