title: Tonic inhibition of chronic pain by neuropeptide Y.
abstract: Dramatically up-regulated in the dorsal horn of the mammalian spinal cord following inflammation or nerve injury, neuropeptide Y (NPY) is poised to regulate the transmission of sensory signals. We found that doxycycline-induced conditional in vivo (Npy(tet/tet)) knockdown of NPY produced rapid, reversible, and repeatable increases in the intensity and duration of tactile and thermal hypersensitivity. Remarkably, when allowed to resolve for several weeks, behavioral hypersensitivity could be dramatically reinstated with NPY knockdown or intrathecal administration of Y1 or Y2 receptor antagonists. In addition, Y2 antagonism increased dorsal horn expression of Fos and phosphorylated form of extracellular signal-related kinase. Taken together, these data establish spinal NPY receptor systems as an endogenous braking mechanism that exerts a tonic, long-lasting, broad-spectrum inhibitory control of spinal nociceptive transmission, thus impeding the transition from acute to chronic pain. NPY and its receptors appear to be part of a mechanism whereby mammals naturally recover from the hyperalgesia associated with inflammation or nerve injury.
authors.affiliation: Tulane University Health Sciences Center, New Orleans, LA 70112, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Solway
authors.forename: Soma C
authors.initials: SC
authors.lastname: Bose
authors.forename: Gregory
authors.initials: G
authors.lastname: Corder
authors.forename: Renee R
authors.initials: RR
authors.lastname: Donahue
authors.forename: Bradley K
authors.initials: BK
authors.lastname: Taylor
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D001552:Benzazepines / Q000494:pharmacology*; D002908:Chronic Disease; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D009478:Neuropeptide Y / Q000378:metabolism*; D009619:Nociceptors / Q000378:metabolism; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism; D020671:Posterior Horn Cells / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D001552:Benzazepines; D009478:Neuropeptide Y; D016760:Proto-Oncogene Proteins c-fos; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; D001120:Arginine; C403256:BIIE 0246; C117416:BIBO 3304