Endogenous substance P inhibits the expression of corticotropin-releasing hormone during a chronic inflammatory stress.

We have investigated the effects of a chronic inflammatory stress on substance P (SP) levels in the hypothalami of rats given adjuvant-induced arthritis (AA). Fourteen days after injection of Mycobacterium butyricum, substance P concentrations in the paraventricular nucleus (PVN) and median eminence/arcuate nucleus were significantly increased. In AA rats injected intraperitoneally with the specific neurokinin-1 receptor antagonist RP67580, plasma ACTH and corticosterone concentrations were significantly elevated, and corticotropin-releasing hormone (CRH) mRNA in the PVN was increased compared to the AA group which received saline alone. The increases in hypothalamic SP in AA, together with the data demonstrating that HPA axis activity is enhanced in AA following injection of a SP antagonist, are consistent with the hypothesis that SP is acting as an inhibitor of CRH expression in this model of chronic inflammatory stress.