The pain relief gel, Cryo-Soothe, offers effective cold therapy and consists of the plant compounds Menthol and Ilex Paraguariensis. While Menthol is considered the active pain-relieving ingredient, Ilex Paraguariensis has been proposed to possess anti-oxidant, anti-inflammatory and anti-mutagenic properties. Menthol exerts its pain relieving effects via a counter-irritant effect; a process in which the application of one irritant (Menthol) counteracts the action of another irritant (Pain).   The counter-irritation stems from an interaction between pain-transmitting and non-pain transmitting neurons. A process coined neuronal gate control. 
The Gate Control Theory of Pain, first described by Melzack and Wall, depicts the involvement of three nerve fibre subtypes in pain transmission: larger, myelinated A-delta fibres involved in the rapid transmission of intense pain signals, smaller, unmyelinated C fibres known to transmit dull, throbbing chronic pain signals and the inhibitory, non-pain transmitting A-beta fibres. The Gate Control Theory states that pain signals transmitted via either A-delta or C fibres can be modulated and weakened by the activation of the inhibitory A-beta fibres. A variety of factors have been proposed to activate these inhibitory fibres. These include: cold therapy, pharmaceutical agents, environmental factors and state of mood. 
Cryo-Soothe, analgesic gel, exerts topical pain relief via the activation of A-beta fibres.  But, little is still known on how Menthol activates these inhibitory fibres. Recently, Menthol has been shown to activate the cold-responsive ion channel, TRPM8 receptor. Moreover, the activation of this receptor has been linked to the pain relieving properties of Menthol.
Cryo-Soothe: Effective Pain Relief
Cold therapies, including Menthol, the active ingredient in Cryo-Soothe, have been used for centuries as an herbal remedy of pain. Recently, doctors and scientists have begun to initiate clinical trials putting Menthol-induced pain relief to the test.
In a first trial, the effectiveness of Menthol transdermal patches was evaluated in a double-blind, parallel-group, placebo-controlled, randomized treatment assignment, multicentre trial of over 200 patients with mild to moderate muscle strain. Findings from this study demonstrated that patients treated with Menthol had significantly improved topical pain relief compared to placebo-treated patients. Furthermore, the majority of Menthol patients rated their pain relief as either very good or good. Moreover, significantly fewer Menthol patients rated their pain relief as poor compared to the placebo group. In this study, the safety of Menthol therapy was also addressed. Most importantly, no significant increase in adverse events was observed in patients treated with Menthol.
A second randomized, double-blind, placebo-controlled trial demonstrated the pain relieving properties of Menthol in a population of patients receiving chiropractic adjustments for chronic lower back pain. Interestingly, a significant reduction in pain was shown following only one week of Menthol treatment.
Another randomized, double-blind, placebo-controlled trial examined pain relief induced by a Menthol-containing herbal remedy in osteoarthritis patients with proven joint involvement. A significant decrease in both joint pain and stiffness was observed following 2 weeks of Menthol treatment. In fact, an astonishing 77% decrease in joint pain and 86% decrease in joint stiffness were observed in Menthol-treated patients. 
Recently, Menthol has been shown to not only reduce pain, but block pain-inducing inflammation. In fact, one study has demonstrated that Menthol ointment application can significantly reduce vascular conductance, the blow flow involved in the initiation of inflammation. More interestingly, the reduction in vascular conductance was observed within 60 seconds of ointment application and that this reduction was maintained for at least 10 minutes following its application.  The vascular effect of Menthol was further confirmed in a second study that demonstrated that Menthol rapidly reduced both arterial blood flow and arterial diameter.
Together, these findings suggest that Menthol, the active ingredient in the pain relief gel Cryo-Soothe, can significantly reduce pain in patients suffering from mild to moderate muscle strains, lower back pain and osteoarthritis. Moreover, this analgesic gel also mediates pain by reducing blood flow that can lead to the development of inflammation. Furthermore, doctors and scientists are actively evaluating the benefits of Menthol in a variety of clinical trials focussed on the pain relieving properties of Menthol in non-complicated neck pain, hand pain and exercise-induced blood flow and pain.
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