title: L1 cell adhesion molecule is essential for the maintenance of hyperalgesia after spinal cord injury.
abstract: Spinal cord injury (SCI) results in a loss of normal motor and sensory function, leading to severe disability and reduced quality of life. A large proportion of individuals with SCI also suffer from neuropathic pain symptoms. The causes of abnormal pain sensations are not well understood, but can include aberrant sprouting and reorganization of injured or spared sensory afferent fibers. L1 is a cell adhesion molecule that contributes to axonal outgrowth, guidance and fasciculation in development as well as synapse formation and plasticity throughout life. In the present study, we used L1 knockout (KO) mice to determine whether this adhesion molecule contributes to sensory dysfunction after SCI. Both wild-type (WT) and KO mice developed heat hyperalgesia following contusion injury, but the KO mice recovered normal response latencies beginning at 4 weeks post-injury. Histological analyses confirmed increased sprouting of sensory fibers containing calcitonin-gene related peptide (CGRP) in the deep dorsal horn of the lumbar spinal cord and increased numbers of interneurons expressing protein kinase C gamma (PKCgamma) in WT mice 6 weeks after injury. In contrast, L1 KO mice had less CGRP(+) fiber sprouting, but even greater numbers of PKCgamma(+) interneurons at the 6 week time point. These data demonstrate that L1 plays a role in maintenance of thermal hyperalgesia after SCI in mice, and implicate CGRP(+) fiber sprouting and the upregulation of PKCgamma expression as potential contributors to this response.
authors.affiliation: Department of Physiology and Cell Biology, The Ohio State University Medical Center, Columbus, OH, USA.
authors.forename: Emily L
authors.initials: EL
authors.lastname: Hoschouer
authors.forename: Feng Qin
authors.initials: FQ
authors.lastname: Yin
authors.forename: Lyn B
authors.initials: LB
authors.lastname: Jakeman
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D020439:Growth Cones / Q000378:metabolism / Q000648:ultrastructure; D006930:Hyperalgesia / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D007395:Interneurons / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D039842:Neural Cell Adhesion Molecule L1 / Q000235:genetics*; D009473:Neuronal Plasticity / Q000235:genetics; D020671:Posterior Horn Cells / Q000166:cytology / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D020127:Recovery of Function / Q000235:genetics; D013116:Spinal Cord / Q000378:metabolism* / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D013126:Spinal Nerve Roots / Q000166:cytology / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
chemical_list: D039842:Neural Cell Adhesion Molecule L1; C087857:protein kinase C gamma; D011493:Protein Kinase C; D015740:Calcitonin Gene-Related Peptide