Increased levels of Homer1b/c and Shank1a in the post-synaptic density of spinal dorsal horn neurons are associated with neuropathic pain in rats.
Activity-dependent plasticity in the spinal dorsal horn may underlie the development of neuropathic pain following peripheral nerve injury. In this study we examined whether the expression and loss of behavioral signs of neuropathic pain were associated with changes in the content of the scaffolding proteins Homer and Shank in the post-synaptic density (PSD) of the spinal dorsal horn. In animals exhibiting thermal hyperalgesia and differential weight-bearing behavior 7 days after loose ligation of the sciatic nerve the levels of Homer1b/c and Shank1a were significantly greater than in control, uninjured or sham-operated animals. These greater levels were specifically a reflection of increases in the injured, ipsilateral and not contralateral dorsal horn. In contrast, there were no differences in the PSD content of Homer1b/c and Shank1a in the dorsal horn of control or sham-operated animals and ligated animals in which the thermal hyperalgesia and differential weight-bearing behavior had disappeared 28 days after the loose ligation. These data revealed a close association between the expression and loss of allodynia and hyperalgesia with changes in the levels of Homer1b/c and Shank1a in the spinal dorsal horn. The reversible shift in the content of scaffolding proteins in the PSD may have important implications for the development of injury-elicited neuropathic pain.
Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706-1102, USA.
Gordana
G
Miletic
Takako
T
Miyabe
Kara J
KJ
Gebhardt
Vjekoslav
V
Miletic
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D000072233:Homer Scaffolding Proteins; D006930:Hyperalgesia / Q000378:metabolism / Q000503:physiopathology; D008026:Ligation; D008297:Male; D009419:Nerve Tissue Proteins; D009437:Neuralgia / Q000378:metabolism* / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000502:physiology; D009475:Neurons, Afferent / Q000378:metabolism; D009619:Nociceptors / Q000378:metabolism; D010523:Peripheral Nervous System Diseases / Q000378:metabolism* / Q000503:physiopathology; D020671:Posterior Horn Cells / Q000378:metabolism* / Q000648:ultrastructure; D017729:Presynaptic Terminals / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020426:Sciatic Neuropathy / Q000378:metabolism / Q000503:physiopathology; D013126:Spinal Nerve Roots / Q000378:metabolism; D013570:Synaptic Membranes / Q000378:metabolism* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D000072233:Homer Scaffolding Proteins; D009419:Nerve Tissue Proteins; C120531:Shank1 protein, rat