ENDOGENOUS SUBSTANCE-P INHIBITS THE DEPRESSION OF CORTICOTROPIN-RELEASING HORMONE DURING A CHRONIC INFLAMMATORY STRESS

We have investigated the effects of a chronic inflammatory stress on s ubstance P (SP) levels in the hypothalami of rats given adjuvant-induc ed arthritis (AA). Fourteen days after injection of Mycobacterium buty ricum, 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 rece ptor 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 receive d saline alone. The increases in hypothalamic SP in AA, together with the data demonstrating that HPA axis activity is enhanced in AA follow ing injection of a SP antagonist, are consistent with the hypothesis t hat SP is acting as an inhibitor of CRH expression in this model of ch ronic inflammatory stress.