Potent analgesic effects of GDNF in neuropathic pain states

被引:421
作者
Boucher, TJ
Okuse, K
Bennett, DLH
Munson, JB
Wood, JN
McMahon, SB [1 ]
机构
[1] Kings Coll London, Ctr Res Neurosci, London SE1 7EH, England
[2] UCL, Dept Biol, London WC1E 6BT, England
关键词
D O I
10.1126/science.290.5489.124
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Neuropathic pain arises as a debilitating consequence of nerve injury. The etiology of such pain is poorly understood, and existing treatment is largely ineffective. We demonstrate here that glial cell line-derived neurotrophic factor (GDNF) both prevented and reversed sensory abnormalities that developed in neuropathic pain models, without affecting pain-related behavior in normal animals. GDNF reduces ectopic discharges within sensory neurons after nerve injury. This may arise as a consequence of the reversal by GDNF of the injury-induced plasticity of several sodium channel subunits. Together these findings provide a rational basis for the use of GDNF as a therapeutic treatment for neuropathic pain states.
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页码:124 / 127
页数:4
相关论文
共 25 条
[1]  
Bennett DLH, 1998, J NEUROSCI, V18, P3059
[2]   Tactile allodynia, but not thermal hyperalgesia, of the hindlimbs is blocked by spinal transection in rats with nerve injury [J].
Bian, D ;
Ossipov, MH ;
Zhong, CM ;
Malan, TP ;
Porreca, F .
NEUROSCIENCE LETTERS, 1998, 241 (2-3) :79-82
[3]   Upregulation of a silent sodium channel after peripheral, but not central, nerve injury in DRG neurons [J].
Black, JA ;
Cummins, TR ;
Plumpton, C ;
Chen, YH ;
Hormuzdiar, W ;
Clare, JJ ;
Waxman, SG .
JOURNAL OF NEUROPHYSIOLOGY, 1999, 82 (05) :2776-2785
[4]  
Boucher TJ, 2000, PROG PAIN RES MANAG, V16, P175
[5]   The expression of P2X3 purinoreceptors in sensory neurons:: Effects of axotomy and glial-derived neurotrophic factor [J].
Bradbury, EJ ;
Burnstock, G ;
McMahon, SB .
MOLECULAR AND CELLULAR NEUROSCIENCE, 1998, 12 (4-5) :256-268
[6]   NT-3 promotes growth of lesioned adult rat sensory axons ascending in the dorsal columns of the spinal cord [J].
Bradbury, EJ ;
Khemani, S ;
King, VR ;
Priestley, JV ;
McMahon, SB .
EUROPEAN JOURNAL OF NEUROSCIENCE, 1999, 11 (11) :3873-3883
[7]   GDNF IS AN AGE-SPECIFIC SURVIVAL FACTOR FOR SENSORY AND AUTONOMIC NEURONS [J].
BUJBELLO, A ;
BUCHMAN, VL ;
HORTON, A ;
ROSENTHAL, A ;
DAVIES, AM .
NEURON, 1995, 15 (04) :821-828
[8]   MYELINATED AFFERENTS SIGNAL THE HYPERALGESIA ASSOCIATED WITH NERVE INJURY [J].
CAMPBELL, JN ;
RAJA, SN ;
MEYER, RA ;
MACKINNON, SE .
PAIN, 1988, 32 (01) :89-94
[9]   Spinal nerve ligation: what to blame for the pain and why [J].
Gold, MS .
PAIN, 2000, 84 (2-3) :117-120
[10]  
KERR BJ, UNPUB