title: Preserved acute pain and impaired neuropathic pain in mice lacking protein interacting with C Kinase 1.
abstract: Protein interacting with C Kinase 1 (PICK1), a PDZ domain-containing scaffolding protein, interacts with multiple different proteins in the mammalian nervous system and is believed to play important roles in diverse physiological and pathological conditions. In this study, we report that PICK1 is expressed in neurons of the dorsal root ganglion (DRG) and spinal cord dorsal horn, two major pain-related regions. PICK1 was present in approximately 29.7% of DRG neurons, most of which were small-less than 750 μm(2) in cross-sectional area. Some of these PICK1-positive cells co-labeled with isolectin B4 or calcitonin-gene-related peptide. In the dorsal horn, PICK1 immunoreactivity was concentrated in the superficial dorsal horn, where it was prominent in the postsynaptic density, axons, and dendrites. Targeted disruption of PICK1 gene did not affect basal paw withdrawal responses to acute noxious thermal and mechanical stimuli or locomotor reflex activity, but it completely blocked the induction of peripheral nerve injury-induced mechanical and thermal pain hypersensitivities. PICK1 appears to be required for peripheral nerve injury-induced neuropathic pain development and to be a potential biochemical target for treating this disorder.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Petralia
authors.forename: Kogo
authors.initials: K
authors.lastname: Takamiya
authors.forename: Jun
authors.initials: J
authors.lastname: Xia
authors.forename: Yun-Qing
authors.initials: YQ
authors.lastname: Li
authors.forename: Richard L
authors.initials: RL
authors.lastname: Huganir
authors.forename: Yuan-Xiang
authors.initials: YX
authors.lastname: Tao
authors.forename: Myron
authors.initials: M
authors.lastname: Yaster
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins; D004705:Endocytosis; D005727:Ganglia, Spinal / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity; D009437:Neuralgia / Q000378:metabolism* / Q000503:physiopathology; D009687:Nuclear Proteins / Q000172:deficiency* / Q000378:metabolism; D020671:Posterior Horn Cells / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; C091822:Prkcabp protein, mouse; D018091:Receptors, AMPA; D015740:Calcitonin Gene-Related Peptide; C104722:glutamate receptor ionotropic, AMPA 2