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

Abstract

PurposeEffective 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 methodsPatients 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.ResultsFifty-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.ConclusionThis 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.

Role of miR-145 in chronic constriction injury in rats

“…Clinically, sciatica and chronic back pain are the most common types of neuropathic pain, and the pathogenesis is complicated (2). The primary causes are the degeneration of the corresponding organs, lumbar disc herniation caused by trauma, nerve damage, calcification of ligaments, bone hyperplasia, inflammation and tumors (3)(4)(5). Due to the long period of clinical treatment, disease recurrence and poor prognosis, the quality of life of patients with neuropathic pain is greatly affected.…”

The role of topiceuticals in cancer pain

“…A recent proof of concept study looked at the potential of menthol as a clinically useful analgesic in patients with chemotherapy induced peripheral neuropathy(CIPN) and scar related pain [35]. This was on the basis of basic science findings that activation of the TRPM8 ion channel by topical agents produced significant analgesia [36].…”

“…This was on the basis of basic science findings that activation of the TRPM8 ion channel by topical agents produced significant analgesia [36]. The small numbered study found that 82% of subjects had an improvement in brief pain inventory (BPI) scores [35].…”

Topical Menthol Gel Versus a Placebo Gel on Postmanipulation Pain and Range of Motion in Patients With Mechanical Neck Pain

“…15 Topical application of menthol has long been considered to be an effective treatment for mild-to-moderate pain. 16 Investigators have confirmed the painrelieving effects of topical application of menthol on a variety of conditions including neuropathic pain, 17 knee osteoarthrosis, 18 and carpal tunnel syndrome.…”