Cancer treatment-related neuropathic pain: proof of concept study with menthol—a TRPM8 agonist

• Published in: Supportive care in cancer Vol. 23; no. 9; pp. 2769 - 2777
• Main Authors: Fallon, M. T., Storey, D. J., Krishan, A., Weir, C. J., Mitchell, R., Fleetwood-Walker, S. M., Scott, A. C., Colvin, L. A.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-09-2015; Springer; Springer Nature B.V
• Subjects: Administration, Topical; Adult; Aged; Aged, 80 and over; Analgesics; Analgesics - therapeutic use; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Cancer; Cancer research; Chemotherapy; Female; Humans; Male; Medicine; Medicine & Public Health; Menthol - therapeutic use; Middle Aged; Neoplasms - drug therapy; Neuralgia - chemically induced; Neuralgia - drug therapy; Neuralgia - psychology; Nursing; Nursing Research; Oncology; Original; Original Article; Pain; Pain management; Pain Medicine; Rehabilitation Medicine; Surveys and Questionnaires; Treatment Outcome; TRPM Cation Channels - agonists; Young Adult; Chemotherapy; Menthol; Pain; TRPM8; Neuropathic; Cancer
• ISSN: 0941-4355; 1433-7339
• DOI: 10.1007/s00520-015-2642-8

Purpose
Effective treatment of neuropathic pain without unacceptable side effects is challenging. Cancer sufferers increasingly live with long-term treatment-related neuropathic pain, resulting from chemotherapy-induced peripheral neuropathy (CIPN) or surgical scars. This proof-of-concept study aimed to determine whether preclinical evidence for TRPM8 ion channels in sensory neurons as a novel analgesic target could be translated to clinical benefit in patients with neuropathic pain, using the TRPM8 activator menthol.
Patients and methods
Patients with problematic treatment-related neuropathic pain underwent a baseline assessment using validated questionnaires, psychophysical testing, and objective functional measures. The painful area was treated with topical 1 % menthol cream twice daily. Assessments were repeated at 4–6 weeks. The primary outcome was the change in Brief Pain Inventory total scores at 4–6 weeks. Secondary outcomes included changes in function, mood and skin sensation.
Results
Fifty-one patients (female/male, 32/19) were recruited with a median age of 61 (ranging from 20 to 89). The commonest aetiology was CIPN (35/51), followed by scar pain (10/51). Thirty-eight were evaluable on the primary outcome. Eighty-two per cent (31/38) had an improvement in total Brief Pain Inventory scores (median, 47 (interquartile range, 30 to 64) to 34 (6 to 59),
P
 < 0.001). Improvements in mood (
P
 = 0.0004), catastrophising (
P
 = 0.001), walking ability (
P
 = 0.008) and sensation (
P
 < 0.01) were also observed.
Conclusion
This proof-of-concept study indicates that topical menthol has potential as a novel analgesic therapy for cancer treatment-related neuropathic pain. Improvements in patient-rated measures are supported by changes in objective measures of physical function and sensation. Further systematic evaluation of efficacy is required.