Is neuronal nitric oxide involved in adjuvant-induced joint inflammation?

Involvement of PKA-dependent upregulation of nNOS–CGRP in adrenomedullin-initiated mechanistic pathway underlying CFA-induced response in rats

“…administration of the receptor agonist rAM 1-50 produces long-lasting hyperalgesia (Ma et al, 2006). In accordance with previous studies (Chu et al, 2005;Pozza et al, 1998), the present study showed that CFA injection induced an increase in the level of nNOS in the spinal dorsal horn and small-and medium-diameter neurons of DRG. Interestingly, the i.t.…”

“…AM 22-52 also inhibits CFA-induced hyperalgesia (Hong et al, 2009), our result is in agreement with the purported role of nNOS in inflammatory hyperalgesia as evidenced by the finding that the i.t. administration of the nNOS inhibitor L-NAME (Chu et al, 2005) or 7-nitroindazole (Chu et al, 2005;Pozza et al, 1998) attenuates inflammatory hyperalgesia. Therefore, the present study suggests that the AM bioactivity in inflammatory pain is ascribed to the enhanced nNOS expression.…”

“…nNOS likely plays an important role in the pathogenesis of inflammatory hyperalgesia because the expression of nNOS in the lumbar spinal dorsal horn (Boettger et al, 2007;Chu et al, 2005) and sensory ganglia (Pozza et al, 1998) is increased in CFA-induced inflammation and i.t. administration of nNOS inhibitor (Osborne and Coderre, 1999;Roche et al, 1996) or depletion of nNOS gene (Boettger et al, 2007;Chu et al, 2005) markedly attenuates inflammatory pain.…”

“…In particular, nNOS contributes to the induction of inflammatory hyperalgesia as evidenced by the increase of expression of nNOS, but not the other isoforms of NOS (inducible NOS and endothelial NOS), in the spinal cord of the CFA model of inflammatory hyperalgesia (Boettger et al, 2007;Chu et al, 2005). Moreover, the administration of nNOS inhibitor (Pozza et al, 1998) or the targeted disruption of the nNOS gene (Chu et al, 2005) markedly attenuated CFA-induced hyperalgesia. The present study was designed to examine the hypothesis that AM recruits nNOS/CGRP cascade in CFA-induced inflammation.…”

Selective Inhibition of Inducible Nitric Oxide Synthase Exacerbates Erosive Joint Disease

“…Deletion of the iNOS gene by homologous recombination in mutant mice renders these animals more susceptible to adjuvant (24) and septic (25) arthritis, consistent with our findings. Significantly, administration of a selective neuronal NOS inhibitor 7-nitroindazole reduced adjuvant-induced joint inflammation in rats (26), suggesting an inexplicable role for nNOS in arthritic pathology. These studies highlight the complexity of the pro-and anti-inflammatory activities of iNOS (27)(28)(29) and define a previously unrecognized role for the constitutively expressed NOS in the evolution of acute and chronic inflammatory synovial pathology.…”