BMC oral health · 2026
Targeting CGRP signaling alleviates cancer-associated pain in oral squamous cell carcinoma.
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Chen Mingtao, Guo Yibo, Liu Zheqi, Lin Chengzhong, Wang Yang, Yang Xi, Ji Tong, Zhang Chenping, Zhang Yu
Аннотация
BACKGROUND: Pain is the most frequent complication in patients with oral squamous cell carcinoma (OSCC) and is associated with poor prognosis. Calcitonin gene-related peptide (CGRP), abundantly expressed in sensory neurons, has been implicated in multiple pain disorders; however, its role in cancer-associated pain remains unclear. We investigated the relationship between CGRP and OSCC-associated pain and evaluated the analgesic potential of Rimegepant, a CGRP-receptor antagonist approved for migraine.
METHODS: Plasma CGRP was measured in OSCC patients and correlated with preoperative pain scores and clinical outcomes over a 30-month follow-up. Immunohistochemistry quantified CGRP within tumor-infiltrating nerve fibers. In a unilateral orthotopic tongue OSCC mouse model, we compared the analgesic effects of Rimegepant with carprofen and tramadol. RNA-sequencing of ipsilateral trigeminal ganglia from treated mice was performed to explore potential mechanisms.
RESULTS: Plasma CGRP levels were positively correlated with patient-reported pain severity and were associated with reduced overall survival. Increased CGRP expression in tumor-infiltrating nerves was linked to greater pain intensity and lymph node metastasis. In an OSCC mouse model, both systemic and local administration of Rimegepant significantly attenuated facial mechanical hypersensitivity. Transcriptomic analysis of trigeminal ganglia, together with RT-qPCR validation, revealed suppression of innate immune and neuroinflammatory pathways following Rimegepant treatment.
CONCLUSIONS: Our findings link sensory-nerve-derived CGRP to OSCC-associated pain and support further evaluation of CGRP receptor antagonism as a potential analgesic strategy in cancer.
METHODS: Plasma CGRP was measured in OSCC patients and correlated with preoperative pain scores and clinical outcomes over a 30-month follow-up. Immunohistochemistry quantified CGRP within tumor-infiltrating nerve fibers. In a unilateral orthotopic tongue OSCC mouse model, we compared the analgesic effects of Rimegepant with carprofen and tramadol. RNA-sequencing of ipsilateral trigeminal ganglia from treated mice was performed to explore potential mechanisms.
RESULTS: Plasma CGRP levels were positively correlated with patient-reported pain severity and were associated with reduced overall survival. Increased CGRP expression in tumor-infiltrating nerves was linked to greater pain intensity and lymph node metastasis. In an OSCC mouse model, both systemic and local administration of Rimegepant significantly attenuated facial mechanical hypersensitivity. Transcriptomic analysis of trigeminal ganglia, together with RT-qPCR validation, revealed suppression of innate immune and neuroinflammatory pathways following Rimegepant treatment.
CONCLUSIONS: Our findings link sensory-nerve-derived CGRP to OSCC-associated pain and support further evaluation of CGRP receptor antagonism as a potential analgesic strategy in cancer.