Cytokines - possible biomarkers for headache syndromes, with special reference to migraine

Abstract

Background: The trigeminovascular theory suggests that neurogenic inflammation and cytokines play an important role in migraine pathophysiology. Previous studies have linked different cytokines to migraine pathogenesis, but the results have been conflicting. Today, no biomarkers are known for primary headaches. The objectives for this thesis were to: 1. Identify cytokines as possible specific biomarkers for migraine, cluster headache and tension-type headache. 2. Define cytokine secretion as possible inflammatory response to pain. 3. Evaluate the use of ELISA assay and ELISpot assay for the purpose of this study. 4. Evaluate strengths and flaws of this pilot study and suggest improvements for future studies. Methods: Too few tension-type headache patients, and no cluster headache patients, agreed to participate in this study. The only headache group consisted of 11 migraineurs. Control groups consisted of 7 low back pain patients and 21 healthy, pain free individuals. Blood samples were taken both during attack/pain period and attack free/pain free period. Peripheral blood mononuclear cell samples were analyzed using ELISpot assay and serum samples were analyzed using multiplex ELISA assay. Frequencies of cytokine secreting cells and blood cytokine levels were determined, and levels of cytokine production were compared within and between groups. Results: A higher frequency of TNF-α secreting cells than IL-10 secreting cells was observed in migraineurs. Lower MCP-1 and IL-10 levels and higher TNF-α levels were observed in both migraineurs and low back pain patients compared to healthy, pain free controls. Conclusions: No cytokines were revealed as possible biomarkers for migraine. A possible upregulation of TNF-α and downregulation of MCP-1 and IL-10 may be of relevance, if not specifically for migraine, at least for pain in general. The results obtained from the ELISpot assay and the ELISA assay were not identical. The two methods provide information about cytokine production from different cell sources. Further investigation of cytokine production and comparison of the two assays are needed.