Effects of inflammation on the ultrastructural localization of spinal cord dorsal horn group I metabotropic glutamate receptors.
Inflammatory pain is thought to induce functional plasticity of spinal dorsal horn neurons and may produce changes in glutamate receptor expression. Plasticity of group I metabotropic glutamate receptors (mGluR1 and mGluR5) is important in various neuronal systems, and these receptors are also known to modulate nociceptive neurotransmission in the spinal dorsal horn. The present study aimed at determining whether persistent inflammatory pain produces alterations in intracellular and plasma membrane-associated mGluR1alpha and mGluR5 in spinal cord dorsal horn. Persistent inflammation was induced in male Long Evans rats by a unilateral intraplantar injection of 100 muL of complete Freund's adjuvant (CFA). Three days after the CFA injection thermal withdrawal latencies were obtained prior to processing of transverse spinal cord sections for preembedding immunogold labeling after incubation in primary antibody for mGluR1alpha or mGluR5. Using electron microscopy, we quantified immunogold-labeled mGluR1alpha and mGluR5 profiles, located in lamina V and I-II, respectively, of both CFA-treated rats and untreated control rats. Compared to untreated rats, CFA-treated rats had a significant increase in the number of plasma membrane-associated mGluR5 immunogold-labeled particles in lamina I-II neurons of the spinal cord. Although no changes to mGluR1alpha expression were found in CFA-treated rats, plasma membrane-associated mGluR1alpha was significantly closer to the synapse. Therefore, in CFA-treated rats there was a specific increase in the ratio of plasma membrane-associated versus intracellular immunogold-labeled particles for mGluR5, and lateral movement of mGluR1alpha toward the synapse, indicating that peripheral inflammation-induced trafficking of group I mGluRs in spinal dorsal horn neurons may be an important factor in the development of plastic changes associated with inflammation-induced chronic pain.
Pitcher
Mark H
MH
Department of Anesthesia, McGill University, Montreal, Quebec, Canada.
Ribeiro-da-Silva
Alfredo
A
Coderre
Terence J
TJ
D000276:Adjuvants, Immunologic / Q000633:toxicity; D000818:Animals; D005620:Freund's Adjuvant / Q000633:toxicity; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007249:Inflammation / Q000139:chemically induced / Q000150:complications / Q000378:metabolism*; D008297:Male; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D009473:Neuronal Plasticity / Q000502:physiology*; D010146:Pain / Q000209:etiology / Q000503:physiopathology; D020671:Posterior Horn Cells / Q000378:metabolism* / Q000648:ultrastructure; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D020318:Rats, Long-Evans; D018094:Receptors, Metabotropic Glutamate / Q000096:biosynthesis*; D013569:Synapses / Q000378:metabolism
D000276:Adjuvants, Immunologic; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D005620:Freund's Adjuvant