Changes in expression of NMDA-NR1 receptor subunits in the rostral ventromedial medulla modulate pain behaviors.
NMDA receptors have an important role in pain facilitation in rostral ventromedial medulla (RVM) and the NR1 subunit is essential for its function. Studies suggest that the NMDA receptors in RVM are critical to modulate both cutaneous and muscle hypersensitivity induced by repeated intramuscular acid injections. We propose that increased expression of the NR1 subunit in the RVM is critical for the full development of hypersensitivity. To test this we used recombinant lentiviruses to over-express the NR1 subunit in the RVM and measured nociceptive sensitivity to cutaneous and muscle stimuli. We also downregulated the expression of NR1 in the RVM and measured the hyperalgesia produced by repeated-acid injections. Increasing the expression of NR1 in the RVM reduces cutaneous and muscle withdrawal threshold, and decreasing the expression of NR1 in the RVM increases the muscle withdrawal threshold and prevents the development of hyperalgesia in an animal model of muscle pain. These results suggest that the NR1 subunits in the RVM are critical for modulating NMDA receptor function, which in turn sets the 'tone' of the nervous system's response to noxious stimuli and tissue injury.
Da Silva
Luis Felipe S
LFS
Veterinary Science Department, Center for Agrarian Sciences, University of Paraiba, Areia, PB 58397-000, Brazil Graduate Program in Physical Therapy and Rehabilitation Sciences, Neuroscience Graduate Program, Pain Research Program, The University of Iowa, Iowa City, IA 52242, USA Internal Medicine, The University of Iowa, Iowa City, IA 52242, USA Department of Pharmacology, Physiology and Neuroscience, University of South Carolina School of Medicine, Columbia, SC 29208, USA.
Walder
Roxanne Y
RY
Davidson
Beverly L
BL
Wilson
Steven P
SP
Sluka
Kathleen A
KA
D000143:Acids / Q000009:adverse effects; D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000502:physiology*; D005822:Genetic Vectors / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics; D006930:Hyperalgesia / Q000503:physiopathology; D016089:Immunodeficiency Virus, Feline / Q000502:physiology; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000294:innervation / Q000378:metabolism / Q000503:physiopathology / Q000821:virology; D010146:Pain / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology*; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D012867:Skin / Q000294:innervation
D000143:Acids; D035683:MicroRNAs; C409466:NR1 NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D049452:Green Fluorescent Proteins