English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

There is increasing evidence that CD4(+) T-cell-dependent responses are associated with the maintenance of neuropathic pain. However, little is known about the precise mechanism(s) underlying the activation of CD4(+) T-cells. We herein show that inhibition of cathepsin S (CatS) activity, either through genetic deletion or via a pharmacological inhibitor, Z-Phe-Leu-COCHO (Z-FL), significantly attenuated the maintenance of tactile allodynia, splenic hypertrophy, increased number of splenic CD4(+) T-cells and the final cleavage step of the MHC class II-associated invariant chain following peripheral nerve injury. It was also noted that splenectomy significantly attenuated the peripheral nerve injury-induced tactile allodynia, whereas the adoptive transfer of splenic CD4(+) T-cells from neuropathic wild-type mice significantly increased the pain level of splenectomized wild-type or CatS(-/-) mice. Furthermore, CatS deficiency or Z-FL treatment also significantly inhibited the infiltration of CD4(+) T-cells that expressed interferon-γ (IFN-γ) in the dorsal spinal cord. Signal transducer and activator of transcription 1, a molecule downstream of IFN-γ receptor activation, was activated exclusively in microglia 7 d after peripheral nerve injury. Moreover, CatS deficiency, Z-FL treatment, or splenectomy significantly attenuated the proliferation of microglia 14 d after peripheral nerve injury. These results show a peripheral pivotal role of CatS in the development of neuropathic pain through the antigen-specific activation of CD4(+) T-cells. After activation, CD4(+) T-cells infiltrate into the dorsal spinal cord and secrete IFN-γ to reactivate microglia, which contribute to the transition of acute pain to a chronic pain state.

Peripheral Role of Cathepsin S in Th1 Cell-Dependent Transition of Nerve Injury-Induced Acute Pain to a Chronic Pain State