The loss of sympathetic nerve fibers is a general principle in inflammatory diseases. Since sympathetic neurotransmitters exert anti-inflammatory effects at increased concentrations, their loss is reasonable to overcome infection but detrimental in chronic inflammatory autoimmune diseases. Semaphorins are major factors involved in axon guidance and repulsion mediated by a neuropilin-2/Plexin A2 receptor-complex on nerve endings. Antagonizing semaphorin might keep nerve fibers in the inflamed area and may be a new therapeutic principle in treatment of rheumatoid arthritis. We found very effective polyclonal antibodies neutralizing the effects of semaphorin 3F-induced nerve fiber repulsion. Based on this finding we generated peptides with high binding capacity to Plexin A2 and Semaphorin 3F. Phage display is a technique to study protein–peptide binding with high throughput of up to 109 different peptides on bacteriophages. On basis of the Phages, we found possible binding sites of Plexin A2 and Semaphorin 3F and created exactly fitting peptides to this hot spots on the proteins. We found different peptides to block the binding sites on Plexin A2, Neuropilin-2 and Semaphorin 3F. First in vitro tests showed nearly complete abrogation of nerve fiber repulsion at protein concentrations of 150 nmol/l. This study provided us with an important tool to manipulate sympathetic nerve fiber repulsion. Next step is testing the effect in an arthritis mouse model.