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Expression of the neuropeptide calcitonin gene‐related peptide (CGRP) in trigeminal ganglion is implicated in neurovascular headaches and temporomandibular joint disorders. Elevation of cytokines contributes to the pathology of these diseases. However, a connection between cytokines and CGRP gene expression in trigeminal ganglion nerves has not been established. We have focused on the effects of the cytokine tumor necrosis factor‐α (TNF‐α). TNFR1 receptors were found on the majority of CGRP‐containing rat trigeminal ganglion neurons. Treatment of cultures with TNF‐α stimulated CGRP secretion. In addition, the intracellular signaling intermediate from the TNFR1 receptor, ceramide, caused a similar increase in CGRP release. TNF‐α caused a coordinate increase in CGRP promoter activity. TNF‐α treatment activated the transcription factor NF‐κB, as well as the Jun N‐terminal kinase (JNK) and p38 …