title: Increased neuronal expression of neurokinin-1 receptor and stimulus-evoked internalization of the receptor in the rostral ventromedial medulla of the rat after peripheral inflammatory injury.
abstract: This study examined possible mechanisms by which Substance P (Sub P) assumes a pronociceptive role in the rostral ventromedial medulla (RVM) under conditions of peripheral inflammatory injury, in this case produced by intraplantar (ipl) injection of complete Freund's adjuvant (CFA). In saline- and CFA-treated rats, neurokinin-1 receptor (NK1R) immunoreactivity was localized to neurons in the RVM. Four days after ipl injection of CFA, the number of NK1R-immunoreactive neurons in the RVM was increased by 30%, and there was a concomitant increase in NK1R-immunoreactive processes in CFA-treated rats. Although NK1R immunoreactivity was increased, tachykinin-1 receptor (Tacr1) mRNA was not increased in the RVM of CFA-treated rats. To assess changes in Sub P release, the number of RVM neurons that exhibited NK1R internalization was examined in saline- and CFA-treated rats following noxious heat stimulation of the hind paws. Only CFA-treated rats that experienced noxious heat stimulation exhibited a significant increase in the number of neurons showing NK1R internalization. These data suggest that tonic Sub P release is not increased as a simple consequence of peripheral inflammation, but that phasic or evoked release of Sub P in the RVM is increased in response to noxious peripheral stimulation in a persistent inflammatory state. These data support the proposal that an upregulation of the NK1R in the RVM, as well as enhanced release of Sub P following noxious stimulation, underlie the pronociceptive role of Sub P under conditions of persistent inflammatory injury.
authors.affiliation: Department of Anesthesia, University of Iowa, Iowa City, Iowa, 52242.
authors.forename: Marta V
authors.initials: MV
authors.lastname: Hamity
authors.forename: Roxanne Y
authors.initials: RY
authors.lastname: Walder
authors.forename: Donna L
authors.initials: DL
authors.lastname: Hammond
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D005620:Freund's Adjuvant / Q000633:toxicity; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006930:Hyperalgesia / Q000473:pathology; D007249:Inflammation / Q000209:etiology* / Q000473:pathology*; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism; D059348:Peripheral Nerve Injuries / Q000139:chemically induced / Q000150:complications*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000235:genetics / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism
chemical_list: D005904:Glial Fibrillary Acidic Protein; D018040:Receptors, Neurokinin-1; D013373:Substance P; D005620:Freund's Adjuvant; D010751:Phosphopyruvate Hydratase
keywords: Substance P; Tacr1; complete Freund's adjuvant; hyperalgesia; nociception