Sphingosine-1-phosphate acting via the S1P1 receptor is a downstream signaling pathway in ceramide-induced hyperalgesia

► Inhibition of sphingosine kinase 1 and 2 prevents ceramide-induced hyperalgesia. ► Inhibition of TNF-α signaling reduces ceramide-induced hyperalgesia. ► The S1P receptor 1 antagonist, W146, blocks ceramide-induced hyperalgesia. ► The S1P pathway may be a novel therapeutic approach in pain management.