Thymic stromal lymphopoietin modification gates chronic pain via regulation of transient receptor potential vanilloid type 1-caspase1.

Aim: Given that depletion of thymic stromal lymphopoietin (TSLP) signals is a potential therapeutic option to relieve chronic pain, in this study, we aimed to explore the role of TSLP in regulation of chronic pain and clarify the interactions between TRPV1 and caspase1.

Methods: Bleomycin (BLM), one derivative of Streptomyces verticellus, was administered into mouse to generate chronic mechanical pain in wild type (WT) mice and TSLP knockout mice. Four groups were divided including WT + saline, WT+BLM, TSLP knockout + saline and TSLP knockout + BLM. Differentiated SH-SY5Y cells were then established as a neuronal cell model. Pain behavioral test, cell viability test, western blot and immunofluorescence staining were used to evaluate the effects of TSLP depletion on glial reaction, neuronal death and inflammation.

Results: Bleomycin enhanced the TRPV1-caspase1 signaling to induce chronic pain in mice. Compared to the mice receiving saline, glial reaction and neuronal death were augmented in the somatosensory cortex of the mice receiving bleomycin. In contrast, bleomycin also activated glial reaction and neuronal death in TSLP knockout mice but to a lower extent than those in WT mice with altered mechanical withdrawal threshold. In differentiated SH-SY5Y cells, silencing of TSLP decreased the expression of TRPV1-caspase1 as well as neuronal death induced by H₂O₂.

Conclusions: By regulating glial reaction, neuronal death and inflammation, TSLP is a candidate target to treat chronic pain along with TRPV1-caspase1.