Building on seminal work from Firestein (15–17) and Straub (86–88), who postulated the CNS as a potential target for the treatment of rheumatic diseases, we experimentally confirmed their previous observations of reduced c-Fos protein expression and p38 phosphorylation locally in the spinal cord after intrathecal application of p38 or TNF-α inhibitors, simply by oral histamine supplementation. The gene discussed is TNF; the disease is rheumatic disorder.