Spinal substance P receptor expression and internalization in acute, short-term, and long-term inflammatory pain states

Inflammatory pain involves the sensitization of both primary afferent and s pinal cord neurons. To explore the neurochemical changes that contribute to inflammatory pain, we have examined the expression and ligand-induced inte rnalization of the substance P receptor (SPR) in the spinal cord in acute, shortterm, and long-term inflammatory pain states. These inflammatory model s included unilateral injection of formalin (8-60 min), carrageenan (3 hr), and complete Freund's adjuvant (CFA; 3 d) into the rat hindpaw as well as adjuvant-induced polyarthritis (21 d). In acute inflammatory pain there is ongoing release of substance P (SP) as measured by SPR internalization in l amina I neurons at both 8 and 60 min after formalin injection. Although the re is no tonic release of SP in short-term inflammatory pain, at 3 hr after carrageenan injection, SP is released in response to both noxious and non- noxious somatosensory stimulation with SPR internalization being observed i n neurons located in both laminae I and III-IV. In long-term inflammatory p ain models (CFA and polyarthritis) the same pattern of SP release and SPR a ctivation occurs as is observed in short-term inflammation with the additio n that there is a significant upregulation of the SPR in lamina I neurons. These results suggest that SPR internalization might serve as a marker of t he contribution of ongoing primary afferent input in acute and persistent p ain states. These stereotypical neurochemical changes suggest that there ar e unique neurochemical signatures for acute, short-term, and long-term infl ammatory pain.