title: Artemin induced functional recovery and reinnervation after partial nerve injury.
abstract: Systemic artemin promotes regeneration of dorsal roots to the spinal cord after crush injury. However, it is unclear whether systemic artemin can also promote peripheral nerve regeneration, and functional recovery after partial lesions distal to the dorsal root ganglion (DRG) remains unknown. In the present investigation, male Sprague Dawley rats received axotomy, ligation, or crush of the L5 spinal nerve or sham surgery. Starting the day of injury, animals received intermittent subcutaneous artemin or vehicle across 2weeks. Sensory thresholds to tactile or thermal stimuli were monitored for 6weeks after injury. Immunohistochemical analyses of the DRG and nerve regeneration were performed at the 6-week time point. Artemin transiently reversed tactile and thermal hypersensitivity after axotomy, ligation, or crush injury. Thermal and tactile hypersensitivity reemerged within 1week of treatment termination. However, artemin-treated rats with nerve crush, but not axotomy or ligation, subsequently showed gradual return of sensory thresholds to preinjury baseline levels by 6weeks after injury. Artemin normalized labeling for NF200, IB4, and CGRP in nerve fibers distal to the crush injury, suggesting persistent normalization of nerve crush-induced neurochemical changes. Sciatic and intradermal administration of dextran or cholera toxin B distal to the crush injury site resulted in labeling of neuronal profiles in the L5 DRG, suggesting regeneration functional restoration of nonmyelinated and myelinated fibers across the injury site into cutaneous tissue. Artemin also diminished ATF3 and caspase 3 expression in the L5 DRG, suggesting persistent neuroprotective actions. A limited period of artemin treatment elicits disease modification by promoting sensory reinnervation of distal territories and restoring preinjury sensory thresholds.
authors.affiliation: Department of Pharmacology, University of Arizona College of Medicine, Tucson, AZ 85724, USA BiogenIdec Inc, 14 Cambridge Center, Cambridge, MA 02142, USA.
authors.forename: Ruizhong
authors.initials: R
authors.lastname: Wang
authors.forename: Anthony
authors.initials: A
authors.lastname: Rossomando
authors.forename: Dinah W Y
authors.initials: DWY
authors.lastname: Sah
authors.forename: Michael H
authors.initials: MH
authors.lastname: Ossipov
authors.forename: Tamara
authors.initials: T
authors.lastname: King
authors.forename: Frank
authors.initials: F
authors.lastname: Porreca
mesh_terms: D000818:Animals; D008297:Male; D020932:Nerve Growth Factor / Q000494:pharmacology*; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology; D013127:Spinal Nerves / Q000187:drug effects* / Q000293:injuries* / Q000378:metabolism
chemical_list: C490887:Artn protein, rat; D009419:Nerve Tissue Proteins; D020932:Nerve Growth Factor
keywords: Artemin; Hyperalgesia; Peripheral nerve injury; Regeneration; Sensory neurons