title: Cancer treatment-related neuropathic pain: proof of concept study with menthol--a TRPM8 agonist.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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: Edinburgh Cancer Research Centre (IGMM), University of Edinburgh, Edinburgh, EH4 2XR, UK, Marie.Fallon@ed.ac.uk.
authors: M T
authors: MT
authors: Fallon
authors: D J
authors: DJ
authors: Storey
authors: A
authors: A
authors: Krishan
authors: C J
authors: CJ
authors: Weir
authors: R
authors: R
authors: Mitchell
authors: S M
authors: SM
authors: Fleetwood-Walker
authors: A C
authors: AC
authors: Scott
authors: L A
authors: LA
authors: Colvin
mesh_terms: D000287:Administration, Topical; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000700:Analgesics / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008610:Menthol / Q000627:therapeutic use*; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D009437:Neuralgia / Q000139:chemically induced / Q000188:drug therapy* / Q000523:psychology; D011795:Surveys and Questionnaires; D050053:TRPM Cation Channels / Q000819:agonists*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000700:Analgesics; D000970:Antineoplastic Agents; D050053:TRPM Cation Channels; C425966:TRPM8 protein, human; D008610:Menthol