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Loose ligation of the rat sciatic nerve elicits early accumulation of Shank1 protein in the post-synaptic density of spinal dorsal horn neurons. 2010

Gordana Miletic, and Catalina I Dumitrascu, and Christopher E Honstad, and Daniela Micic, and Vjekoslav Miletic
Department of Anesthesiology, School of Medicine and Public Health, University of Wisconsin, 1300 University Avenue, Madison, WI 53706, USA.

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.

UI MeSH Term Description Entries
D008026 Ligation Application of a ligature to tie a vessel or strangulate a part. Ligature,Ligations,Ligatures
D008297 Male Males
D009419 Nerve Tissue Proteins Proteins, Nerve Tissue,Tissue Proteins, Nerve
D006930 Hyperalgesia An increased sensation of pain or discomfort produced by minimally noxious stimuli due to damage to soft tissue containing NOCICEPTORS or injury to a peripheral nerve. Hyperalgesia, Tactile,Hyperalgesia, Thermal,Hyperalgia,Hyperalgia, Mechanical,Hyperalgia, Primary,Hyperalgia, Secondary,Allodynia,Allodynia, Mechanical,Allodynia, Tactile,Allodynia, Thermal,Hyperalgesia, Mechanical,Hyperalgesia, Primary,Hyperalgesia, Secondary,Hyperalgesic Sensations,Mechanical Allodynia,Mechanical Hyperalgesia,Tactile Allodynia,Thermal Allodynia,Allodynias,Hyperalgesias,Hyperalgesias, Thermal,Hyperalgesic Sensation,Mechanical Hyperalgia,Mechanical Hyperalgias,Primary Hyperalgia,Primary Hyperalgias,Secondary Hyperalgia,Secondary Hyperalgias,Sensation, Hyperalgesic,Sensations, Hyperalgesic,Thermal Hyperalgesia
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D017207 Rats, Sprague-Dawley A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company. Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats
D048868 Adaptor Proteins, Signal Transducing A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymes Signal Transducing Adaptor Proteins
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus
D055366 Synaptic Potentials The voltages across pre- or post-SYNAPTIC MEMBRANES. Postsynaptic Current,Postsynaptic Potentials,Synaptic Potential,Current, Postsynaptic,Currents, Postsynaptic,Postsynaptic Currents,Postsynaptic Potential,Potential, Postsynaptic,Potential, Synaptic,Potentials, Postsynaptic
D020426 Sciatic Neuropathy Disease or damage involving the SCIATIC NERVE, which divides into the PERONEAL NERVE and TIBIAL NERVE (see also PERONEAL NEUROPATHIES and TIBIAL NEUROPATHY). Clinical manifestations may include SCIATICA or pain localized to the hip, PARESIS or PARALYSIS of posterior thigh muscles and muscles innervated by the peroneal and tibial nerves, and sensory loss involving the lateral and posterior thigh, posterior and lateral leg, and sole of the foot. The sciatic nerve may be affected by trauma; ISCHEMIA; COLLAGEN DISEASES; and other conditions. (From Adams et al., Principles of Neurology, 6th ed, p1363) Sciatic Nerve Diseases,Lesion of Sciatic Nerve,Neuralgia-Neuritis, Sciatic Nerve,Sciatic Nerve Palsy,Sciatic Neuritis,Nerve Disease, Sciatic,Nerve Diseases, Sciatic,Nerve Lesion, Sciatic,Nerve Lesions, Sciatic,Nerve Palsies, Sciatic,Nerve Palsy, Sciatic,Neuralgia Neuritis, Sciatic Nerve,Neuralgia-Neuritides, Sciatic Nerve,Neuritides, Sciatic,Neuritis, Sciatic,Neuropathies, Sciatic,Neuropathy, Sciatic,Palsies, Sciatic Nerve,Palsy, Sciatic Nerve,Sciatic Nerve Disease,Sciatic Nerve Lesion,Sciatic Nerve Lesions,Sciatic Nerve Neuralgia-Neuritides,Sciatic Nerve Neuralgia-Neuritis,Sciatic Nerve Palsies,Sciatic Neuritides,Sciatic Neuropathies

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