What is a PAR 2 Inhibitor?

Protease Activated Receptor 2 is abundantly produced by almost all cell types, especially in keratinocytes and itch sensitive C-fibre endings. This, in essence, the third leg of inflammation after erythema and edema. Adding a Par 2 inhibitor to Lorenol® II helps block pain and itch often associated with inflammatory skin issues.


Par 2:

  • Is the “Crosstalk between mast cells and nerve endings” (itch sensitive, unmyelinated C-fibers) signaling itching to the brain

  • Links erythema and edema in the “triangle effect” (Itch and pain typically go hand in hand)

Activation of PAR 2 induces:

  • The release of neuropeptides like CGRP (calcitonin gene-related peptide) and SP (substance P) from sensory nerve endings, triggering itch and inflammation pathways

  • Mast cell degranulation via SP release

  • Up-regulation of inflammation mediators like IL8 and IL6

  • Itch signaling to the brain

  • Neurogenic inflammation, and nociception (via activation of the TPRV1 receptor)

Accumulating evidence of the effects of PAR 2 activation can be found in research related to:

  • Aged Skin

  • Atopic Dermatitis (AD)

  • Barrier Homeostasis

  • Dry skin (Skin Toning)

  • Itchy Skin

  • Inflammation

  • Predisposed AD

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Mast cell activation releases tryptase, one site of action for which is PAR-2, a receptor located on adjacent C neurone terminals and causes them to release substance P. Substance P activates dermal mast cells via NK1 receptors, resulting in increased release of TNF-α, which in turn sensitises nociceptor nerve terminals, and enhances their responsiveness. The antipruritic capsaicin desensitises C neurones and depletes substance P from terminals via VR-1 receptors. TNF=tumour necrosis factor; TNF-R=TNF receptor; H1=histamine H1 receptor; PAR=proteinase activated receptor; NK1=neurokinin receptor 1; SP=substance P; VR1=vanilloid receptor 1.


Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(03)12570-6/fulltext