title: Intrathecally administered Sema3A protein attenuates neuropathic pain behavior in rats with chronic constriction injury of the sciatic nerve.
abstract: Semaphorins, one of the repulsive axonal guidance factors during development, are produced under pathological conditions in adult animals. In the neuropathic pain state associated with peripheral nerve injury, synaptic reorganization occurs in spinal cord dorsal horn. In the present study, we investigated the roles of intrathecal administration of Sema3A, a secreted semaphorin, in the spinal cord of chronic constriction injury (CCI) model rat. Neuropilin 1 (NPR1) and Plexin A (PlexA), co-receptors of Sema3A, were expressed in the dorsal horn of naïve rats. NPR1, and not PlexA, protein expression increased in the dorsal spinal cord of CCI rats. Recombinant Sema3A protein attenuated mechanical allodynia and heat hyperalgesia in CCI rats, whereas heat-inactivated Sema3A had no effect. Immunohistochemistry revealed that Sema3A partially restored the decrease of isolectin B4-positive unmyelinated nerve terminals in lamina II of the ipsilateral dorsal horn of CCI rats. Contrary to our expectations, Sema3A did not change the distribution of myelinated fibers in lamina II at 7 days after CCI. Those results suggested that the suppressive role for Sema3A in the development of neuropathic pain associated with peripheral nerve injury in adult rats, which seemed to be independent from prevention of the myelinated fiber sprouting into lamina II.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Yokohama City University Graduate School of Medicine, Kanazawa-ku, Yokohama, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Hayashi
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Kamiya
authors.forename: Hideki
authors.initials: H
authors.lastname: Itoh
authors.forename: Tomoko
authors.initials: T
authors.lastname: Higashi
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Miyazaki
authors.forename: Kengo
authors.initials: K
authors.lastname: Funakoshi
authors.forename: Naoya
authors.initials: N
authors.lastname: Yamashita
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Goshima
authors.forename: Tomio
authors.initials: T
authors.lastname: Andoh
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Yamada
authors.forename: Takahisa
authors.initials: T
authors.lastname: Goto
mesh_terms: D000818:Animals; D003251:Constriction, Pathologic / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism; D006930:Hyperalgesia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007278:Injections, Spinal; D037102:Lectins / Q000378:metabolism; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009437:Neuralgia / Q000378:metabolism* / Q000473:pathology; D010523:Peripheral Nervous System Diseases / Q000378:metabolism / Q000473:pathology; D020671:Posterior Horn Cells / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012584:Sciatic Nerve / Q000378:metabolism / Q000503:physiopathology; D020426:Sciatic Neuropathy / Q000378:metabolism*; D040121:Semaphorin-3A / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D013116:Spinal Cord / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D013569:Synapses; D053675:Versicans
chemical_list: D006023:Glycoproteins; D037102:Lectins; D009419:Nerve Tissue Proteins; C492115:Plxna2 protein, rat; D011956:Receptors, Cell Surface; D040121:Semaphorin-3A; C508324:Vcan protein, rat; D053675:Versicans; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A