Nesfatin-1 and Ghrelin/GOAT as Novel Biomarkers in Adolescent Headache with Temporomandibular Disorders

Abstract Background: Nesfatin-1 and Ghrelin are recently discovered peptide hormones with roles beyond energy homeostasis. This study investigated Nesfatin-1 and Ghrelin O-acetyltransferase (Ghrelin/GOAT) levels in adolescents with headaches and analyzed their correlation with temporomandibular disorders (TMD) symptoms. Methods: We measured Nesfatin-1 and Ghrelin/GOAT levels in the serum and saliva of 44 adolescents with headaches (aged 10-17 years) and 20 controls without headaches or TMD symptoms. TMD was evaluated using Diagnostic Criteria for TMD (DC/TMD) axis I and II. Participants underwent comprehensive clinical examination and biochemical analysis. Results: Significant differences were found in Nesfatin-1 and Ghrelin/GOAT levels between patients and controls (p<0.001). Nesfatin-1 levels were consistently elevated in all headache patients' blood and saliva regardless of headache type or TMD status. Ghrelin/GOAT showed a distinctive tissue-specific pattern: serum concentrations were higher (p<0.001), while salivary levels were lower (p<0.001) compared to controls. Gender-specific differences were observed in TMD manifestations: muscle pain with palpation was more common in females (74% vs 38%, p<0.016), while psychological distress was more prevalent in males (90% vs 48%, p<0.003). No significant differences in neuroendocrine markers were found between migraine and tension-type headache groups. Conclusions: Altered Nesfatin-1 and Ghrelin/GOAT levels may serve as important biomarkers for adolescent headache, regardless of TMD status. The tissue-specific regulation of Ghrelin/GOAT and gender-specific clinical manifestations highlight the complex interplay between neuroendocrine factors and pain perception. These findings provide new insights into potential diagnostic markers and therapeutic targets for adolescent headache and TMD management.