Lumbar 5 ventral root transection-induced upregulation of nerve growth factor in sensory neurons and their target tissues: a mechanism in neuropathic pain.
We have previously demonstrated that profound and persistent neuropathic pain as displayed by mechanical and cold allodynia and thermal hyperalgesia can be produced by a lumbar 5 ventral root transection (L5 VRT) model in adult rats in which only the motor nerve fibers were injured without axotomy of sensory neurons. However, the underlying mechanisms remain to be determined. In this study, by examining its changes in expression and by inhibiting its functions using a neutralizing antibody, we have investigated whether nerve growth factor (NGF), a neurotrophic factor known to have a function in regulating nerve injury-induced pain, is involved in the development of neuropathic pain induced by L5 VRT. Motor nerve injury by L5 VRT resulted in a de novo expression of NGF mRNA in a subpopulation of small sensory neurons and pericellular satellite cells in ipsilateral L5 dorsal root ganglion. NGF protein expression was also increased by sensory neurons with various sizes and by keratinocytes in the target tissue ipsilateral skin. Systemic administration of NGF antiserum twice within 17 days markedly attenuated L5 VRT-induced mechanical allodynia but not the cold allodynia and thermal hyperalgesia. These findings suggest that NGF is an important pain mediator in the generation of mechanical sensitivity induced by L5 VRT.
Li
Li
L
Department of Human Physiology and Center for Neuroscience, Flinders University of South Australia, GPO Box 2100, Adelaide 5001, Australia. li.li@flinders.edu.au
Xian
Cory J
CJ
Zhong
Jin-Hua
JH
Zhou
Xin-Fu
XF
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D003714:Denervation; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism*; D006930:Hyperalgesia / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D020932:Nerve Growth Factor / Q000037:antagonists & inhibitors / Q000172:deficiency* / Q000235:genetics; D009437:Neuralgia / Q000378:metabolism* / Q000503:physiopathology; D009475:Neurons, Afferent / Q000166:cytology / Q000378:metabolism*; D017288:Pain Threshold / Q000502:physiology; D010523:Peripheral Nervous System Diseases / Q000378:metabolism* / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000235:genetics; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D019051:Rhizotomy / Q000009:adverse effects*; D027161:Satellite Cells, Perineuronal / Q000166:cytology / Q000378:metabolism; D012867:Skin / Q000166:cytology / Q000294:innervation / Q000378:metabolism; D013126:Spinal Nerve Roots / Q000293:injuries* / Q000601:surgery; D015854:Up-Regulation / Q000502:physiology*
D000906:Antibodies; D012333:RNA, Messenger; D017475:Receptors, Nerve Growth Factor; D020932:Nerve Growth Factor