TRPV3 Channel in Keratinocytes in Scars with Post-Burn Pruritus

Abstract

Post-burn pruritus is a common and distressing sequela of burn scars. Empirical antipruritic treatments usually fail to have a satisfactory outcome because of their limited selectivity and possible side effects. Therefore, novel drug targets need to be identified. Here, we aimed to investigate the possible role of protease-activated receptor 2 (PAR2) and transient receptor potential vanniloid 3 (TRPV3), along with the relation of TRPV3 to thymic stromal lymphopoietin (TSLP). Specimens from normal (unscarred) or burn-scarred (with or without pruritus) tissue were obtained from burn patients for this study. In each sample, the keratinocytes were isolated and cultured, and the intracellular Ca2+ level at the time of stimulation of each factor was quantified and the interaction was screened. PAR2 function was reduced by antagonism of TRPV3. Inhibiting protein kinase A (PKA) and protein kinase C (PKC) reduced TRPV3 function. TSLP mRNA and protein, and TSLPR protein expressions, increased in scars with post-burn pruritus, compared to scars without it or to normal tissues. In addition, TRPV1 or TRPV3 activation induced increased TSLP expression. Conclusively, TRPV3 may contribute to pruritus in burn scars through TSLP, and can be considered a potential therapeutic target for post-burn pruritus.

Aberrant Expression of Histamine-independent Pruritogenic Mediators in Keratinocytes may be Involved in the Pathogenesis of Prurigo Nodularis

“…Moreover, increased epidermal TSLP and TSLPR have been reported in scars with post-burn pruritus compared with scars without pruritus or normal tissues. Additionally, an enhanced number of epidermal PGP 9.5-positive nerve fibres has also been observed in scars with post-burn pruritus, suggesting that higher expression of TSLP-TSLPR in epidermis is related to neurohyperplasia in post-burn scars (33). In PN lesions, no intraepidermal neurohyperplasia has been reported, but intraepidermal neurohypoplasia has been observed (18,26,34).…”

Genetic Signature of Acute Lymphoblastic Leukemia and Netherton Syndrome Co-incidence—First Report in the Literature

“…Activation of TRPV3 in skin keratinocytes causes skin barrier formation, hair growth, wound healing, temperature sensing, itch, and pain perception (27). Its dysfunction leads to the occurrence of Olmsted syndrome (28), allergic dermatitis (29), and also promotes the formation of scars (30). Potentially, the coexistence of SPINK5 and TRPV3 mutations could lead to a more aggressive course of NS, but so far, this relationship has not been described in the literature.…”

Nerve reinnervation and itch behavior in a rat burn wound model

“…These local mediators include those produced by keratinocytes, like nerve growth factor, acting on tyrosine kinase A receptors and thymic stromal lymphopoietin (TSLP) acting on TSLP receptors, while others are produced by mast cells, like serotonin and tryptase, which act on serotonin and PAR2 receptors respectively. Most of these receptors are G protein coupled receptors, which use various transient receptor potential (TRP) ion channels, especially TRPV1, TRPV3, and TRPA1 to exert their effect on neurons . In addition, Toll‐like and Mas‐related G‐protein coupled receptor A3 are also involved in producing itch …”

“…Most of these receptors are G protein coupled receptors, which use various transient receptor potential (TRP) ion channels, especially TRPV1, TRPV3, and TRPA1 to exert their effect on neurons. 41 In addition, Toll-like and Mas-related G-protein coupled receptor A3 are also involved in producing itch. 42 In addition to the various peripheral mediators and receptors, there may are also mechanisms in the spinal cord that may lead to increased sensitivity to the activity of itch fibers, 43 which further adds to the complexity of itch produced by burn wounds.…”