Contribution of degeneration of motor and sensory fibers to pain behavior and the changes in neurotrophic factors in rat dorsal root ganglion.
To elucidate the role of the degeneration of motor and sensory fibers in neuropathic pain, we examined the pain-related behaviors and the changes of brain-derived neurotrophic factor (BDNF) in the L4/5 dorsal root ganglion (DRG) and the spinal cord after L5 ventral rhizotomy. L5 ventral rhizotomy, producing a selective lesion of motor fibers, produced thermal hyperalgesia and increased BDNF expression in tyrosine kinase A-containing small- and medium-sized neurons in the L5 DRG and their central terminations within the spinal cord, but not in the L4 DRG. Furthermore, L5 ventral rhizotomy up-regulated nerve growth factor (NGF) protein in small to medium diameter neurons in the L5 DRG and also in ED-1-positive cells in the L5 spinal nerve, suggesting that NGF synthesized in the degenerative fibers is transported to the L5 DRG and increases BDNF synthesis. On the other hand, L5 ganglionectomy, producing a selective lesion of sensory fibers, produced heat hypersensitivity and an increase in BDNF and NGF in the L4 DRG. These data indicate that degeneration of L5 sensory fibers distal to the DRG, but not motor fibers, might influence the neighboring L4 nerve fibers and induce neurotrophin changes in the L4 DRG. We suggest that these changes of neurotrophins in the intact primary afferents of neighboring nerves may be one of many complex mechanisms, which can explain the abnormal pain behaviors after nerve injury. The ventral rhizotomy and ganglionectomy models may be useful to investigate the pathophysiological mechanisms of neuropathic pain after Wallerian degeneration in motor or sensory or mixed nerve.
Obata
Koichi
K
Department of Anatomy and Neuroscience, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
Yamanaka
Hiroki
H
Dai
Yi
Y
Mizushima
Toshiyuki
T
Fukuoka
Tetsuo
T
Tokunaga
Atsushi
A
Yoshikawa
Hideki
H
Noguchi
Koichi
K
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D048429:Cell Size / Q000502:physiology; D003714:Denervation; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000378:metabolism* / Q000473:pathology; D006930:Hyperalgesia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008161:Lumbosacral Region; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009046:Motor Neurons / Q000378:metabolism / Q000473:pathology*; D020932:Nerve Growth Factor / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism*; D009437:Neuralgia / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D009475:Neurons, Afferent / Q000378:metabolism / Q000473:pathology*; D010523:Peripheral Nervous System Diseases / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D017729:Presynaptic Terminals / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D020917:Receptor, trkA; D019051:Rhizotomy; D013126:Spinal Nerve Roots / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation / Q000502:physiology; D014855:Wallerian Degeneration / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology
D019208:Brain-Derived Neurotrophic Factor; D002352:Carrier Proteins; D008565:Membrane Proteins; D009414:Nerve Growth Factors; D020932:Nerve Growth Factor; D020917:Receptor, trkA