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6240501 
Book/Book Chapter 
CHAPTER 17 - Characterization of Pain Receptors in the Spinal Cord Using a Viral Vector for Spatial–Temporal Gene Targeting 
Inturrisi, CE 
2006 
Academic Press 
Amsterdam 
Gene Therapy of the Central Nervous System 
223-229 
Abstract The purpose of this chapter is to describe the use of viral vectors to facilitate a spatial and temporal loss of function mutation. The goal of these studies was to spatially localize the deletion so that the locus and contribution of the gene of interest to pain transmission and amplification could be unequivocally established. The gene target is the NR1 subunit of the N-methyl-d-aspartate (NMDA) receptor. To determine the importance of the NMDA receptor in pain hypersensitivity following injury, the NR1 subunit was selectively deleted in the lumbar spinal cord of adult mice by the localized injection of an adeno-associated virus expressing the Cre recombinase into floxed NR1 mice. NR1 subunit mRNA and dendritic protein are reduced by 80% in the area of the virus injection and NMDA, but not AMPA, currents are abolished in lamina II neurons. The spatial NR1 knockout does not alter heat or cold paw withdrawal latencies, mechanical threshold, or motor function. However, injury-induced pain produced by intraplantar formalin is reduced by 70%. Our results demonstrate conclusively that the postsynaptic NR1 receptor subunit in the lumbar dorsal horn of the spinal cord is required for central sensitization, the central facilitation of pain transmission produced by peripheral injury. 
NMDA receptor; conditional knockout; Cre-loxP; injury-induced pain; fromalin; spinal cord dorsal horn; adeno-associated virus; synaptic transmission; central sensitization 
Kaplitt, Michael G.