RESUMO
Head and neck squamous cell carcinoma (HNSCC) is painful, and perineural invasion (PNI) has been associated with worst pain. Pain due to HNSCC is diverse and may vary based on clinicopathological factors. This study aims to characterize different pain patterns linked with PNI, its influence on daily functioning, and gain insights into molecular changes and pathways associated with PNI-related pain in HNSCC patients. We conducted a cross-sectional study across three medical centers (n=114), assessing pain phenotypes and their impact on daily functioning using two self-reported pain questionnaires, given to patients prior to their cancer surgery. Furthermore, we conducted RNA-seq analysis utilizing the TCGA dataset of HNSCC tumor from patients (n=192) to identify genes relevant to both PNI and pain. Upon adjusting for demographic and clinicopathological variables using linear regression models, we found that PNI independently predicted function-evoked pain according to the UCSF Oral Cancer Pain Questionnaire, as well as the worst pain intensity reported in the Brief Pain Inventory. Distinct pain patterns were observed to be associated with daily activities in varying manners. Our molecular analyses revealed significant disruptions in pathways associated with extracellular matrix (ECM) structure and organization. The top differentially expressed genes linked to the ECM are implicated in cancer development, pain, and neurodegenerative diseases. Our data underscore the importance of properly categorizing pain phenotypes in future studies aiming to uncover mechanistic underpinnings of pain. Additionally, we have compiled a list of genes of interest that could serve as targets for both cancer and cancer pain management. PERSPECTIVE: PNI independently predicts function-evoked pain. Different pain phenotypes affect daily activities differently. We identified a list of candidate genes involved in extracellular matrix structure and function that can be targeted for both cancer and cancer pain control.