Tachykinin receptor modulators: novel therapeutics for rheumatoid arthritis

The activation of a cellular immune response in a genetically susceptible individual is widely recognised as a main step in triggering rheumatoid arthritis (RA). The tachykinins, substance P (SP) and neurokinin A (NKA), can play a major role in different immune diseases. In patients with inflammatory joint disease, elevated levels of SP have been demonstrated in the synovial fluid of affected joints. It is well known that SP and, to a lesser extent, NKA are deeply involved in the processing of nociceptive signals and exert many pro-inflammatory actions, which may be elicited by an increased neuronal neurokinin release in arthritis; the mechanism behind this increase remains to be fully elucidated. Different observations suggest that one approach to the treatment of RA might be to inhibit the local effects of neurokinins in the affected joints. This review will summarise the more relevant aspects of this topic.