Neurogenic inflammation is caused by neuropeptides which are released by peripheral neurons and induce inflammatory signals. Two of the main neuropeptides involved are substance P (SP) and calcitonin gene related peptide (CGRP),1 both acting through several molecular mechanisms including activation of transient receptor potential vanilloid (TRPV) cation channels, particularly TRPV1 (also called vanilloid receptor type 1 or capsaicin (CAP) receptor).2 ,3 SP and CGRP have been found increased in synovial fluid from rheumatoid arthritis (RA) patients4 ,5 and may induce the production of interleukin (IL)-6 and IL-8 in RA synoviocytes,6 suggesting that neuropeptides may have a role in joint inflammation during RA. Interestingly, TRPV cation channels are expressed in various non-neuronal cell types and, recently, they have been found expressed in human synoviocytes.7

No previous study has investigated the possible link among SP, CGRP and TRPV channels in the inflammation process driven by RA synoviocytes. The aim of our work was to investigate whether SP, CGRP and CAP, a potent activator (agonist) of TRPV1, can increase IL-6 and IL-8 production by RA and healthy fibroblast-like synoviocytes, and whether neuropeptides may modulate TRPV1 expression in RA and healthy cells. Synoviocytes were obtained from knee-biopsy of three patients with active RA diagnosed according to the American College of Rheumatology 1987 revised criteria undergoing surgical joint replacement. Patients had not received any disease-modifying antirheumatic drug treatment. Healthy synoviocytes were collected from knee-biopsy of three subjects who underwent surgical intervention after accidental trauma. Synoviocytes (passage 2–4) were cultured at confluence, serum-starved for 24 h and incubated for …