The role of CXCL10/ CXCR3 axis in pain and itch of cutaneous neurofibroma

Cutaneous neurofibroma (cNF), the most common subtype of neurofibroma, is a prevalent peripheral nerve sheath tumor characterized by varying degrees of pain and itch. Due to its disfiguring nature, cNF can cause considerable physical and emotional distress. Moreover, pain and itch substantially impair the quality of life in cNF patients, resulting in significant management challenges. However, the thorough characterization and underlying mechanisms of cNFs and its sensory symptoms are inadequately understood. Coupled with the absence of effective treatment options, this compounds the burden on patients' lives posed by symptomatic cNF. Recent observations have highlighted the significant role of C-X-C Motif Chemokine Receptor 3 (CXCR3)/ C-X-C motif chemokine ligand 10 (CXCL10) in the development of neurofibroma in murine models. CXCL10, a member of the CXC chemokine family, exerts its function via a specific receptor CXCR3, which is present in various immune cell types. Additionally, the association of CXCL10/CXCR3 with the transmission of pain and itch sensations has been established. Crucially, key components of the cNF microenvironment include immune cells such as mast cells, macrophages, T cells, and neutrophils, which can interact with CXCL10/CXCR3. This interaction has the potential to activate itch and pain pathways seen in various inflammatory conditions and cancers. Therefore, we hypothesize that CXCL10/CXCR3 plays a role in pain and itch in cutaneous neurofibroma. Accordingly, our study aims to characterize the features of symptomatic cNFs and propose potential targets for addressing the pain and itch associated with cNFs.