Neurocosmetics are treatments designed to stimulate or inhibit neuro receptors in skin. Neurosensory receptors located in skin have a profound impact on consumer perception of cooling, warming, stinging, burning, itching, tightness, and pain. All cooling and warming sensates currently used in cosmetic formulations work by activating these receptors and some irritation caused by cosmetics is related to the activation of specific types of neurosensory receptors.
The skin contains sensory receptors that can detect touch/pressure (mechanoreceptors), pain (nociceptors), and temperature (thermoreceptors) and these receptors are found in the upper layers of the epidermis.
Neuro responsive transient receptor potential cation channels (TRP channels) are a family of receptors that respond to cold, heat, and pain that occur at neurons. Temperature sensation is dependent on thermosensitive nerve cells present in the epidermis and dermis. A signal is triggered by the flow of intracellular Calcium ions across the temperature activated TRP ion channels. This increases the Calcium concentration into the nerve cell which induces an impulse. TRP channels consist of six protein families located mostly on the plasma membrane of numerous cell types and there are about 28 TRP channels that share structural similarities (1).
Warming/cooling sensates all work by activating different TRP channels. The challenge in using sensates is that all produce some irritation along with a cooling or warming response. Different parts of the body vary significantly in their sensory response depending on the localized concentration of TRPs present and how fast the sensates penetrate skin.
Relative Skin Sensitivity to Cooling: Eyes>>Tongue>Interior Buccal Region>Ano-Genital Area>Lips>Trigeminal Area>Other Face Areas>Armpits>Inside Forearm, Breast>Other Arm Areas, Thigh, Back>Hands, Feet>>Palm, Soles (2)
Different TRPs have been identified that respond to different temperature ranges (6)
- TRPV-3 (32-39C) and TRPV-4 (27-35C) are heat receptors
- TRPV-1 (>43C) and TRPV-2 (>52C) are heat/pain receptors
- TRPA-1 cold/pain (<17C), TRPM-8 cold (<25-28C)
- TRPV3 and TRPV4 activation can positively influence skin barrier formation. TRPV3 activation has been shown to control keratinocyte migration, wound healing and to stimulate skin growth factors TGF-α/ EGF
- TRPV-1, 3, 4, TRPA-1 are produced by Keratinocytes
The only warming sensate currently used in skincare is Vanillyl Butyl Ether (VBE), which is known to activate the TRPV-1 channel and induce vasodilation. VBE used at topically at .4% takes several minutes to be noticeable and produces its maximum heat response after around 15 minutes with approximately 30% of subjects experiencing burning, stinging, or redness reactions. Thermolat (Vanillyl Butyl Ether (and) 1,2-Hexanediol (and) Caprylyl Glycol (and) Ascorbyl Palmitate, 40% active-Symrise) claims to help reduce VBE induced skin irritation by inhibiting the TREK-1 receptor using 1,2 Hexanediol (7). A novel application of VBE is to use a low level combined with a coolant to intensify the cooling response. This suggests that the reverse may be true to intensify the warming response.
All cooling sensates activate the TRPM-8 receptor with most being noticeable within 1 to 2 minutes after application. They typically have a duration of around 10-15 minutes. Menthol is the most common and least expensive coolant used in personal care products however it has disadvantages having of having a strong smell bitter taste/odor, and causing a burning/stinging sensation in some consumers. Derivatives of Menthol are currently used that have reduced smell and irritation however most do not provide the same cooling intensity as Menthol and are significantly more expensive. The commonly used Menthol derivatives include Menthyl Lactate, Menthoxypropanediol, Menthanediol and Menthone Glycerin Acetal.
In the US, approximately 51% of women and 38% of men claim to have sensitive or very sensitive skin. In sensitive skin, the nerve response to stimuli are exaggerated and many of the negative reactions consumers experience may due to over stimulation of neuroreceptors like TRPV-1 (3). This can cause burning, stinging, and tingling sensations in skin. Activation of TRVP-1 can also cause inflammation by activating NF-KB which can cause the release of inflammatory cytokines. Commonly used ingredients like Retinol, Phenoxyethanol, and Benzyl alcohol have been shown to activate TRPV-1 and cause stinging/burning reactions. TRPV-1 inhibitors like SymSitive 1609 (Pentylene Glycol (and) 4-t-Butylcyclohexanol-Symrise) have been shown to reduce these types of reactions (4). Combining a TRPV1-inhibitor with a anti-inflammatory can further improve subjective and objective symptoms of sensitive skin: Eye stinging reactions may also be related to TRPV-1 activation (9). Children products marketed as no more tears/tear free have been shown not to induce TRPV1 activation compared to regular shampoos (5).
Neurosensory receptor activators are approved by the FDA as topical counter irritants for pain relief. Counter irritants represent a class of analgesics that can activate TRPs and desensitize or over activate pain sensory receptors. This results in a sensation that can override the feeling of pain. Approved actives include Menthol, Camphor, Methyl Salicylate, and Capsaicin.
- R.Watson, et. al., New compounds with the menthol cooling effect. Soc. Cosmet. Chem., 29, 185-200 (1978).
- US patent 2014/0364418A1, Johnson and Johnson, December 11, 2014.
- Inada, Tominaga. Cellular Engineering vol. 26. No. 8. 2007 (in Japanese)
- Thermolat presentation (Symrise)
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One Response to “Cool Off or Warm Up with Neurocosmetics”
A very informative and interesting article.