Objective. - To investigate changes in the levels of calcitonin gene- related peptide and its intracellular messenger cyclic adenosine monophosphate in serial samples of internal jugular blood taken from migraine patients without aura assessed during attacks, and to assess their relationship with the levels of IL- 8, MCP- 1, and RANTES in the same samples. Background. - Calcitonin gene- related peptide, the marker of trigeminovascular activation, is released in both the internal and external jugular venous blood of migraine patients during attacks. Experimental evidence demonstrated that when released from C- type sensory neurons in inflammatory pain models, it differentially induced expression of neutrophil chemotactic chemokine IL- 8, but not monocyte chemotactic chemokine MCP- 1 or lymphocyte chemotactic chemokine RANTES. These chemokines were never investigated in migraine. Design/Methods. - Eight migraine without aura patients were admitted to the hospital during the attacks. Internal jugular venous blood samples were taken immediately after catheter insertion, at the 1st, 2nd, and 4th hours after attack onset, and within 2 hours from its cessation. The levels of the sensory neuropeptide calcitonin gene- related peptide and the messenger cyclic adenosine monophosphate were measured by RIA method, and those of IL- 8, MCP- 1,and RANTES were measured by ELISA method. Results. - Higher calcitonin gene- related peptide levels were found in the internal jugular venous blood of migraine without aura patients compared with the time of catheter insertion (ANOVA: P < .0001) with a peak at the first hour (52.6 ± 9.2 ng/mL). A transient increase in IL- 8 was observed at the 2nd and 4th hours (P < .01 and P < .002, respectively), whereas no changes in the levels of MCP- 1 and RANTES were found at any time of the study. The increase in IL- 8 was accompanied by a parallel increase in cyclic adenosine monophosphate. Conclusions. - The present study confirms previous findings of an increase in calcitonin gene- related peptide in internal jugular venousblood of migraine without aura patients during attacks. The transient increase in the levels of IL- 8 concurs with the results of recent experimental research showing a calcitonin gene- related peptide- induced activation of IL- 8 gene expression, but not RANTES and MCP- 1, via the transcriptional factor AP- 2, which mediates transduction in response to cyclic adenosine monophosphate. Although IL- 8 is transiently increased during migraine attacks, an accumulation of leukocytes secondary to neurogenic inflammation is unlikely, as it is for other inflammatory events, because they are self limiting. Other events, including nitric oxide production, may contribute to counteract meningeal transvascular leukocyte migration during migraine attacks, as suggested by the model of sterile inflammation. Objective-To investigate changes in the levels of calcitonin gene-related peptide and its intracellular messenger cyclic adenosine monophosphate in serial samples of internal jugular blood taken from migraine patients without aura assess during attacks, and to assess their relationship with the levels of IL- 8, MCP-1, and RANTES in the same samples. Background. - Calcitonin gene-related peptide, the marker of trigeminovascular activation, is released in both the internal and external jugular venous blood of migraine patients during attacks. Experimental evidence of that when released from C-type sensory neurons in inflammatory pain models, it differentially induced expression of neutrophil chemotactic chemokine IL-8, but not monocyte chemotactic chemokine MCP-1 or lymphocyte chemotactic chemokine RANTES. These chemokines were never investigated in migraine. Design / Methods. - Eight migraine without aura patients were admitted to the hospital during the attacks. Inte rnal jugular venous blood samples were taken immediately after catheter insertion, at the 1st, 2nd, and 4th hours after attack onset, and within 2 hours from its cessation. The levels of the sensory neuropeptide calcitonin gene- related peptide and the messenger cyclic adenosine monophosphate were measured by RIA method, and those of IL-8, MCP-1, and RANTES were measured by ELISA method. Results. - Higher calcitonin gene- related peptide levels were found in the internal jugular venous blood of migraine without aura patient compared with (ANOVA: P <.0001) with a peak at the first hour (52.6 ± 9.2 ng / mL). A transient increase in IL-8 was observed at the 2nd and 4th hours (P <.01 and P <.002, respectively), no changes in the levels of MCP-1 and RANTES were found at any time of the study. The increase in IL-8 was accompanied by a parallel increase in cyclic adenosine monophosphate. Conclusions. - The present study confirms previous findings oThe transient increase in the levels of IL-8 concurs with the results of recent experimental research showing a calcitonin gene-related peptide-induced activation of IL-8 gene expression, but not RANTES and MCP-1, via the transcriptional factor AP-2, which mediates transduction in response to cyclic adenosine monophosphate. IL-8 is transiently increased during migraine attacks, an accumulation of leukocytes secondary to neurogenic inflammation events are unlikely as as is for other inflammatory events, because they are self limiting.