Background & Aims
Pain and itch commonly accompany malignant diseases, posing
significant challenges for effective management of cancer patients. In cutaneous
neurofibroma (cNF), both pain and itch further diminish patients’ quality of life.
Understanding the underlying causes of these symptoms and developing successful treatments are ongoing pursuits. Recent research has highlighted the role of emerging inflammatory chemokines, such as the CXCL10/CXCR3 axis, in neurofibroma progression and its pain and itch disorders.
Our study aims to evaluate the correlation between CXCL10/CXCR3 and the clinical or pathological features of pain and itch cutaneous neurofibromas.
Methods
Patients with solitary neurofibroma were evaluated based on clinical, and pathological findings. The severity of pain and itch with detailed characterization is documented by the Short-form McGill Pain Questionnaire and Eppendorf Itch Questionnaire. The expression of CXCL10/CXCR3 and its association of immune cells were evaluated in the pathological samples by
immunohistochemical and immunofluorescence staining from patients with solitary neurofibroma. Also, the stained areas were quantified to look for the association between expression of these cytokines and other factors such as patient characteristics, size and distribution of tumor, itch, and pain symptoms will be assessed.
Results
We have analyzed pain, itch, and pathology profiling of 42 human cutaneous neurofibroma. Interestingly, there is male predominance in the patients reporting pain (male: female = 10:1). Among the current 42 NF specimens, we have observed a trend for increased tumor sizes and depth in the patients reporting pain (p=0.03 and p=0.03, respectively). For the symptomatic patients, there is significant higher dermal and tumoral CXCR3 signals for both pain and itchy NF (p<0.0001 and p=0.03), for pain NF (p<0.0001 and p= 0.04), and for itchy NF (p=0.0005 and p=0.053) suggesting that CXCL10-CXCR3 axis may be involved in the pain and itch for NF.
Conclusions
CXCL10-CXCR3 signaling may exerts a significant influence on local immune and nervous systems, resulting in pain and itch in solitary NF in human. This suggests that the therapy targeting CXCL10-CXCR3 can help to eliminate solitary NF tumor and also its pain and itch symptoms.
References
Guiraud, M., et al., Cutaneous neurofibromas: patients’ medical burden, current management and therapeutic expectations: results from an online European patient community survey. Orphanet Journal of Rare Diseases, 2019. 14: p. 1-11.
Brosseau, J.-P., et al., The biology of cutaneous neurofibromas: consensus recommendations for setting research prioritiesBrosseau, J.-P., et al., The biology of cutaneous neurofibromas: consensus recommendations for setting research priorities. Neurology, 2018. 91(2 Supplement 1): p. S14-S20.. Neurology, 2018. 91(2 Supplement 1): p. S14-S20.
Jouhilahti, E.-M., et al., The development of cutaneous neurofibromas. The American journal of pathology, 2011. 178(2): p. 500-505.
Fletcher, J.S., et al., Cxcr3-expressing leukocytes are necessary for neurofibroma formation in mice. JCI insight, 2019. 4(3).
Pawlik, K., et al., Blockade of CC Chemokine Receptor Type 3 Diminishes Pain and Enhances Opioid Analgesic Potency in a Model of Neuropathic Pain. Front Immunol, 2021. 12: p. 781310.
Presenting Author
Pham Quoc Thao Trang
Poster Authors
Quoc Thao Trang Pham
MD
Taipei Medical University
Lead Author
Chung-Ping Liao MD.
PhD.
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University
Lead Author
Hao-Jui Weng MD.
PhD.
Department of Dermatology, Taipei Medical University-Shuang Ho Hospital
Lead Author
Topics
- Models: Chronic Pain - Neuropathic