Role of CGRP-mediated neuroinflammation in trigeminal nerve injury

Abstract

Background. Calcitonin gene-related peptide (CGRP) is associated with various types of pain, with elevated levels noted in musculoskeletal pain. Trigeminal nerve injury (TNI), often resulting from facial fractures, can lead to chronic orofacial pain and neuroinflammation, contributing to atypical trigeminal neuralgia. Aim: CGRP is crucial in migraine and headache disorders, with elevated α-CGRP levels linked to trigeminal neuralgia, migraine, and cluster headaches. This study examined the role of CGRP in neuroinflammation following trigeminal nerve injury. Method: Four tissue samples from each oral quadrant (upper left, upper right, lower left, lower right) were collected from six patients post-TNI. Samples were fixed, cryosectioned, and immunohistochemically stained for CGRP. Analysis was performed using a Nikon epifluorescence microscope, recording CGRP levels and measuring fluorescence intensity in relative fluorescence units (RFU). Statistical analysis was conducted using ANOVA. Results. CGRP levels showed distinct patterns. In patient 1, values ranged from 67.7 RFU to 75.3 RFU in each oral quadrant. For patient 2, values ranged from 68.94 RFU to 72.45 RFU. Control values varied between 68.42 RFU and 72.7 RFU. These variations indicate differences in neuroinflammation and nerve function alterations, highlighting the differential impact of nerve injury on facial regions. Twopoint discrimination tests showed thresholds of 3.1 mm for the inferior alveolar nerve and 2.8 mm for the infraorbital nerve, with statistical analysis confirming significance (p < 0.05). Conclusion. The results confirmed that CGRP plays a significant role in neuroinflammation with distinct patterns across different oral quadrants, indicating region-specific neuroinflammatory responses. These findings support the importance of targeted therapeutic strategies for managing neuropathic pain and neuroinflammation, emphasizing CGRP as a critical mediator in these processes.