Investigation of the relationship between headache and neuroinflammatory neuropeptides in patients with mild head trauma

Objective: This study aimed to investigate the relationship between plasma levels of neuroinflammatory neuropeptides, including CGRP, SP, VIP, and PACAP-38, and the development of headache in patients with mild traumatic brain injury (TBI). Materials and Methods: A total of 40 patients aged 18-70 with mild TBI and 40 individuals in the control group were included in the study. Venous blood samples were collected in EDTA tubes from volunteers and centrifuged at 4000 rpm for 15 minutes. Plasma levels of CGRP, SP, PACAP-38, and VIP neuropeptides were measured using the ELISA method. Additionally, VAS scores were evaluated for patients on the first day and after 2 months post-trauma. Results: The mean age of all participants was 40.3 ± 15.9. When comparing CGRP, PACAP-38, SP, and VIP levels between healthy controls and patients on the 0th day post-trauma, all showed a significant increase (p<0.001). Similarly, comparing the levels of these neuropeptides between patients on the 0th and 60th days post-trauma revealed a significant increase (p<0.001). No significant relationship was found between CGRP, PACAP-38, SP, and VIP levels in patients with positive and negative CT scans on the 0th day post-trauma (p=0.017, p=0.023, p=0.266, p=0.231, respectively). The same lack of relationship was observed in patients on the 60th day post-trauma (p=0.604, p=0.705, p=0.705, p=0.769, respectively). The comparison of VAS scores between patients on the 0th and 60th days post-trauma showed a significant difference (p<0.001). VAS scores were higher in patients with positive CT scans on the 0th day, but no significant difference was found between patients with positive and negative CT scans on the 60th day (p=0.347, p=0.9, respectively). A weak correlation between CGRP and VIP has been found, and this correlation is statistically significant (rho=0.38, p=0.015). Conclusion: Our findings have demonstrated that changes in the levels of CGRP, PACAP-38, SP, and VIP neuropeptides may play a role in headache mechanisms in patients with minor TBI after head trauma. Understanding the relationship between traumatic brain injury-induced headaches and neuropeptides is a crucial step in developing potential treatment strategies. KEYWORDS: CGRP, PACAP-38, SP, VIP, Mild traumatic brain injury, VAS scor