Sciatic nerve injury in adult rats causes distinct changes in the central projections of sensory neurons expressing different glial cell line-derived neurotrophic factor family receptors

• Published in: Journal of comparative neurology (1911) 2010-08, Vol.518 (15), p.3024-3045
• Main Authors: Keast, Janet R., Forrest, Shelley L., Osborne, Peregrine B.
• Format: Article
• Language: English
• Subjects: Animals; Cell Count; Ganglia, Spinal - metabolism; Ganglia, Spinal - pathology; Glial Cell Line-Derived Neurotrophic Factor Receptors - biosynthesis; Glial Cell Line-Derived Neurotrophic Factor Receptors - genetics; Immunohistochemistry; lumbosacral; Male; Nerve Fibers - pathology; Nerve Tissue Proteins - metabolism; Neurturin - metabolism; nociceptor; pain; Pain Measurement; Phenotype; Posterior Horn Cells - metabolism; Rats; Rats, Sprague-Dawley; regeneration; Sciatic Nerve - injuries; Sciatic Nerve - pathology; Sensory Receptor Cells - metabolism; Sensory Receptor Cells - pathology; spinal cord; Spinal Cord - metabolism; sprouting; Up-Regulation
• ISSN: 0021-9967; 1096-9861
• DOI: 10.1002/cne.22378

Most small unmyelinated neurons in adult rat dorsal root ganglia (DRG) express one or more of the coreceptors targeted by glial cell line‐derived neurotrophic factor (GDNF), neurturin, and artemin (GFRα1, GFRα2, and GFRα3, respectively). The function of these GDNF family ligands (GFLs) is not fully elucidated but recent evidence suggests GFLs could function in sensory neuron regeneration after nerve injury and peripheral nociceptor sensitization. In this study we used immunohistochemistry to determine if the DRG neurons targeted by each GFL change after sciatic nerve injury. We compared complete sciatic nerve transection and the chronic constriction model and found that the pattern of changes incurred by each injury was broadly similar. In lumbar spinal cord there was a widespread increase in neuronal GFRα1 immunoreactivity (IR) in the L1‐6 dorsal horn. GFRα3‐IR also increased but in a more restricted area. In contrast, GFRα2‐IR decreased in patches of superficial dorsal horn and this loss was more extensive after transection injury. No change in calcitonin gene‐related peptide‐IR was detected after either injury. Analysis of double‐immunolabeled L5 DRG sections suggested the main effect of injury on GFRα1‐ and GFRα3‐IR was to increase expression in both myelinated and unmyelinated neurons. In contrast, no change in basal expression of GFRα2‐IR was detected in DRG by analysis of fluorescence intensity and there was a small but significant reduction in GFRα2‐IR neurons. Our results suggest that the DRG neuronal populations targeted by GDNF, neurturin, or artemin and the effect of exogenous GFLs could change significantly after a peripheral nerve injury. J. Comp. Neurol. 518:3024–3045, 2010. © 2010 Wiley‐Liss, Inc.