TRPM8 Activators for Peripheral Neuropathy

Peripheral neuropathy (PN) is a condition characterized by damage or dysfunction of the peripheral nerves, leading to sensory, motor, or autonomic impairments. Symptoms often include numbness, tingling, burning sensations, muscle weakness, and paresthesia. Chemotherapy-induced peripheral neuropathy (CIPN) and diabetic peripheral neuropathy (DPN) are two of the most prevalent causes of PN. Current pharmacological treatments, such as analgesics, anticonvulsants, antidepressants, and opioids, often provide limited efficacy and are frequently associated with significant adverse effects.

Study Rationale and Mechanism of Action:

The "Speedell" hand and foot mask is a novel product formulated to act primarily as a TRPM8 activator. TRPM8 is a non-selective cation channel with six transmembrane domains, widely expressed in human nerve cells. Upon activation by temperatures between 8-28°C or by specific agonists, TRPM8 generates cold signals that are transmitted to the somatosensory cortex.

Scientific literature suggests that the activation of TRPM8-whether by agonists or moderate cooling-induces the release of glutamate at central synapses. This glutamate subsequently activates inhibitory group II/III metabotropic glutamate receptors (mGluRs) located on injured nociceptive afferent neurons or postsynaptic receptors in the dorsal horn, thereby attenuating neuropathic hypersensitivity.

Furthermore, Speedell is designed to deliver natural cooling agents efficiently to the extremities, where they interact with TRPM8 receptors to provide immediate sensory relief. Evidence suggests that these components may contribute to the reduction of tissue damage caused by cellular inflammation. This pilot study aims to clinically validate the efficacy of the Speedell hand and foot mask in alleviating neuropathic discomfort and improving quality of life in patients suffering from chemotherapy-induced or diabetic peripheral neuropathy.

Inclusion criteria

• Patients aged 20 years or older who are currently receiving or have previously received chemotherapy and have clinical features of chemotherapy-induced peripheral neuropathy (CIPN).
• Diabetic patients aged 20 years or older who have clinical features of diabetic peripheral neuropathy (DPN).
• Patients who meet criteria 1 or 2, are willing to participate, and are able to sign an informed consent form.

Exclusion criteria

• Poorly controlled diabetes (HbA1c > 8%).
• Peripheral vascular disease.
• Chronic kidney disease (eGFR < 30 ml/min/m²).
• Depression, history of surgery on the hands, feet, or back.
• Skin conditions such as leprosy and connective tissue disorders, familial neuropathy.
• Pregnant or breastfeeding women.
• Individuals with allergic symptoms.
• Individuals with a history of convulsions.
• Individuals with G6PD deficiency (favism).