title: Spinal substance P receptor expression and internalization in acute, short-term, and long-term inflammatory pain states.
abstract: Inflammatory pain involves the sensitization of both primary afferent and spinal cord neurons. To explore the neurochemical changes that contribute to inflammatory pain, we have examined the expression and ligand-induced internalization of the substance P receptor (SPR) in the spinal cord in acute, short-term, and long-term inflammatory pain states. These inflammatory models 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 lamina I neurons at both 8 and 60 min after formalin injection. Although there 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 in neurons located in both laminae I and III-IV. In long-term inflammatory pain models (CFA and polyarthritis) the same pattern of SP release and SPR activation occurs as is observed in short-term inflammation with the addition 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 the contribution of ongoing primary afferent input in acute and persistent pain states. These stereotypical neurochemical changes suggest that there are unique neurochemical signatures for acute, short-term, and long-term inflammatory pain.
authors.affiliation: Neurosystems Center, Department of Preventive Sciences, Psychiatry and Neuroscience, University of Minnesota, Minneapolis, Minnesota 55455, USA.
authors.forename: P
authors.initials: P
authors.lastname: Honor
authors.forename: P M
authors.initials: PM
authors.lastname: Menning
authors.forename: S D
authors.initials: SD
authors.lastname: Rogers
authors.forename: M L
authors.initials: ML
authors.lastname: Nichols
authors.forename: A I
authors.initials: AI
authors.lastname: Basbaum
authors.forename: J M
authors.initials: JM
authors.lastname: Besson
authors.forename: P W
authors.initials: PW
authors.lastname: Mantyh
mesh_terms: D000208:Acute Disease; D000344:Afferent Pathways / Q000502:physiology / Q000503:physiopathology; D000818:Animals; D002351:Carrageenan; D002908:Chronic Disease; D005557:Formaldehyde; D005620:Freund's Adjuvant; D007249:Inflammation / Q000503:physiopathology*; D008297:Male; D009474:Neurons / Q000502:physiology; D010146:Pain / Q000503:physiopathology*; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000235:genetics* / Q000378:metabolism*; D013116:Spinal Cord / Q000502:physiology / Q000503:physiopathology*; D013997:Time Factors
chemical_list: D018040:Receptors, Neurokinin-1; D005557:Formaldehyde; D002351:Carrageenan; D005620:Freund's Adjuvant