title: Expression and functional role of metallothioneins I and II in the spinal cord in inflammatory and neuropathic pain models.
abstract: In this study, the expression and functional role of metallothioneins I and II (MT-I/II) were evaluated in the spinal cord in rat models of inflammatory and neuropathic pain. Complete Freund's adjuvant (CFA) injection into the hindpaw induced an increase in MT-I/II protein expression in bilateral dorsal and ventral horns throughout the spinal cord, while chronic constriction injury (CCI) of the sciatic nerve induced an increase in MT-I/II expression in the ipsilateral dorsal and ventral horns of the lower lumbar spinal cord. Increased MT-I/II immunoreactivity was predominantly localized to vascular endothelial cells. CFA injection- and CCI-induced MT-I/II expression was inhibited by intrathecal administration of MT-I siRNA. Treatment with MT-I siRNA before CFA injection or at early time points after CCI resulted in a significant attenuation of mechanical allodynia and thermal hyperalgesia, while treatment at later time points had no effect on established pain behaviors. Our results suggest that endogenous MT-I/II might play an important role in the pathogenesis of pain behaviors, participating in the initiation of inflammatory and neuropathic pain rather than in their maintenance.
authors.affiliation: Department of Anatomy, School of Medicine, Kyungpook National University, 2-101, Dongin Dong, Daegu 702-422, South Korea.
authors.forename: Aram
authors.initials: A
authors.lastname: Kwon
authors.forename: Sang-Min
authors.initials: SM
authors.lastname: Jeon
authors.forename: Sung-Hun
authors.initials: SH
authors.lastname: Hwang
authors.forename: Jong-Heon
authors.initials: JH
authors.lastname: Kim
authors.forename: Hee-Jung
authors.initials: HJ
authors.lastname: Cho
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D015153:Blotting, Western; D003251:Constriction, Pathologic / Q000473:pathology; D005620:Freund's Adjuvant; D007150:Immunohistochemistry; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology*; D007278:Injections, Spinal; D008297:Male; D008668:Metallothionein / Q000096:biosynthesis* / Q000502:physiology*; D009437:Neuralgia / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology*; D034741:RNA, Small Interfering / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D013116:Spinal Cord / Q000378:metabolism* / Q000502:physiology*
chemical_list: D000276:Adjuvants, Immunologic; D034741:RNA, Small Interfering; D005620:Freund's Adjuvant; D008668:Metallothionein
keywords: ANOVA; BBB; BSCB; CCI; CFA; COX-2; Endothelial cell; GLT1; ICAMs; IL; Inflammatory pain; L; MM RNA; MTs; Metallothionein; Neuropathic pain; PECAMs; RT-PCR; SEM; Spinal cord; analysis of variance; blood-brain barrier; blood-spinal cord barrier; chronic constriction injury; complete Freund's adjuvant; cyclooxygenase-2; glucose transporter 1; intercellular adhesion molecules; interleukin; lumbar; metallothioneins; mismatch RNA; platelet-endothelial cellular adhesion molecules; reverse transcription-polymerase chain reaction; standard errors of the mean