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

Abstract

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.

• Authors: M T Fallon, D J Storey, A Krishan, C J Weir, R Mitchell, S M Fleetwood-Walker, A C Scott, L A Colvin
• Journal: Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer (Support Care Cancer) Vol. 23 Issue 9 Pg. 2769-77 (Sep 2015) ISSN: 1433-7339 [Electronic] Germany
• PMID: 25680765 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics
• Antineoplastic Agents
• TRPM Cation Channels
• TRPM8 protein, human
• Menthol

Topics

• Administration, Topical
• Adult
• Aged
• Aged, 80 and over
• Analgesics (therapeutic use)
• Antineoplastic Agents (adverse effects, therapeutic use)
• Female
• Humans
• Male
• Menthol (therapeutic use)
• Middle Aged
• Neoplasms (drug therapy)
• Neuralgia (chemically induced, drug therapy, psychology)
• Surveys and Questionnaires
• TRPM Cation Channels (agonists)
• Treatment Outcome
• Young Adult