title: Loose ligation of the rat sciatic nerve elicits early accumulation of Shank1 protein in the post-synaptic density of spinal dorsal horn neurons.
abstract: Plasticity in the spinal dorsal horn may contribute to the development of pain following peripheral nerve injury. Shank proteins are a constituent family of the post-synaptic density (PSD), and they may play a role in synaptic plasticity through activity-dependent synaptic remodeling and growth. In this study we examined the early consequences of the loose ligation of the sciatic nerve on Shank1 protein and message levels in the PSD of spinal dorsal horn neurons. Four hours after sciatic ligation, the protein levels of Shank1 increased in the ipsilateral PSD of ligated animals. In contrast, no changes were detected in the contralateral PSD of these ligated animals, or either the ipsilateral or contralateral PSD of sham-operated animals. Shank1 was linked to the PSD marker protein PSD-95 and the NR2B subunit of NMDA receptors. The ligated animals also exhibited two early signs of pain behavior, a shift in weight distribution and thermal hyperalgesia. There was no overall change in Shank1 message in either ligated or sham-operated animals. The accumulation of Shank1 in the PSD was abolished by intrathecal pre-treatment with anisomycin or Shank1 siRNA, but not with non-target siRNA. The same pre-treatment prevented both the early signs of pain behavior. Intrathecal pre-treatment with either MK-801 or U0126 similarly prevented the Shank1 accumulation and alleviated both the behavioral signs of pain. The early accumulation of Shank1 in the PSD of dorsal horn neurons may be a necessary step in the injury-associated plasticity that in time leads to the development of persistent pain.
authors.affiliation: Department of Anesthesiology, School of Medicine and Public Health, University of Wisconsin, 1300 University Avenue, Madison, WI 53706, USA.
authors.forename: Gordana
authors.initials: G
authors.lastname: Miletic
authors.forename: Catalina I
authors.initials: CI
authors.lastname: Dumitrascu
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Honstad
authors.forename: Daniela
authors.initials: D
authors.lastname: Micic
authors.forename: Vjekoslav
authors.initials: V
authors.lastname: Miletic
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D006930:Hyperalgesia / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D008026:Ligation; D008297:Male; D009419:Nerve Tissue Proteins; D020671:Posterior Horn Cells / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020426:Sciatic Neuropathy / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D055366:Synaptic Potentials
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D009419:Nerve Tissue Proteins; C120531:Shank1 protein, rat