 |
Previous Article | Next Article 
The Journal of Neuroscience, July 1, 2001, 21(13):4891-4900
Brain-Derived Neurotrophic Factor Increases in the Uninjured
Dorsal Root Ganglion Neurons in Selective Spinal Nerve Ligation
Model
Tetsuo
Fukuoka,
Eiji
Kondo,
Yi
Dai,
Norio
Hashimoto, and
Koichi
Noguchi
Department of Anatomy and Neuroscience, Hyogo College of Medicine,
1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan
Nerve growth factor (NGF) and brain-derived neurotrophic factor
(BDNF) are two major members of the neurotrophin family. Using immunohistochemistry and in situ hybridization
histochemistry, we examined the effect of L5 spinal nerve
ligation (SPNL), a neuropathic pain model, on the expression of BDNF in
the uninjured L4 dorsal root ganglion (DRG). After L5 SPNL, both
immunoreactivity for BDNF and the hybridization intensity for BDNF mRNA
increased mainly in the small- and medium-sized neurons. The percentage
of BDNF mRNA-expressing neurons increased in the ipsilateral L4 DRG
compared with the contralateral DRG from the third to 28th day after
ligation. A significantly greater number of BDNF-immunoreactive neurons were observed in the ipsilateral L4 DRG than contralateral side 14 d after ligation. To test the contribution of BDNF to the thermal hyperalgesia produced in this model, we intrathecally injected anti-BDNF antibody at third day after ligation. This treatment clearly
attenuated thermal hyperalgesia for a few hours. Almost all BDNF
mRNA-expressing neurons coexpressed trkA, a high-affinity NGF receptor,
mRNA. The percentage of BDNF mRNA-expressing cells of trkA cells
significantly increased in the ipsilateral L4 DRG 14 d after
ligation. Furthermore, we examined the contribution of NGF on this
phenotypic change using ELISA, Northern blot analysis, and
anti-NGF antibody. NGF content in the ipsilateral L4 DRG linearly increased and reached a statistical significant level 14 d after L5 SPNL. Moreover, at this time point, the increase in NGF mRNA was
observed in the ipsilateral L5 DRG and sciatic nerve, but not in the
ipsilateral L4 DRG or L4 spinal nerve. Local application of anti-NGF
antibody to the L4 spinal nerve beside the L5 spinal nerve-ligation
site prevented the development of thermal hyperalgesia for 5 d
after ligation. Our data suggest that BDNF, which increased in the
uninjured L4 DRG neurons, acts as a sensory neuromodulator in the
dorsal horn and contributes to thermal hyperalgesia in this neuropathic
pain model. The contribution of locally synthesized NGF to thermal
hyperalgesia was also demonstrated. These dynamic alterations in the
expression and content of BDNF and NGF in the uninjured DRG neurons
might be involved in the pathomechanisms of neuropathic pain.
Key words:
BDNF; NGF; trkA; thermal hyperalgesia; dorsal root
ganglion; neuropathic pain model
Copyright © 2001 Society for Neuroscience 0270-6474/01/21134891-10$05.00/0
This article has been cited by other articles:

|
 |

|
 |
 
T Kondo, K Obata, K Miyoshi, J Sakurai, J Tanaka, H Miwa, and K Noguchi
Transient receptor potential A1 mediates gastric distention-induced visceral pain in rats
Gut,
October 1, 2009;
58(10):
1342 - 1352.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
X. Wang, J. Ratnam, B. Zou, P. M. England, and A. I. Basbaum
TrkB Signaling Is Required for Both the Induction and Maintenance of Tissue and Nerve Injury-Induced Persistent Pain
J. Neurosci.,
April 29, 2009;
29(17):
5508 - 5515.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. Miyoshi, K. Obata, T. Kondo, H. Okamura, and K. Noguchi
Interleukin-18-Mediated Microglia/Astrocyte Interaction in the Spinal Cord Enhances Neuropathic Pain Processing after Nerve Injury
J. Neurosci.,
November 26, 2008;
28(48):
12775 - 12787.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. Chen, C. Geis, and C. Sommer
Activation of TRPV1 Contributes to Morphine Tolerance: Involvement of the Mitogen-Activated Protein Kinase Signaling Pathway
J. Neurosci.,
May 28, 2008;
28(22):
5836 - 5845.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. Saito, S. Hitomi, I. Suzuki, Y. Masuda, J. Kitagawa, Y. Tsuboi, M. Kondo, B. J. Sessle, and K. Iwata
Modulation of Trigeminal Spinal Subnucleus Caudalis Neuronal Activity Following Regeneration of Transected Inferior Alveolar Nerve in Rats
J Neurophysiol,
May 1, 2008;
99(5):
2251 - 2263.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Ma and R. H. LaMotte
Multiple Sites for Generation of Ectopic Spontaneous Activity in Neurons of the Chronically Compressed Dorsal Root Ganglion
J. Neurosci.,
December 19, 2007;
27(51):
14059 - 14068.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Mizuno, T. Takebayashi, T. Kirita, K. Tanimoto, N. Tohse, and T. Yamashita
The effects of the sympathetic nerves on lumbar radicular pain: A BEHAVIOURAL AND IMMUNOHISTOCHEMICAL STUDY
J Bone Joint Surg Br,
December 1, 2007;
89-B(12):
1666 - 1672.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
V. B. Lu, K. Ballanyi, W. F. Colmers, and P. A. Smith
Neuron type-specific effects of brain-derived neurotrophic factor in rat superficial dorsal horn and their relevance to 'central sensitization'
J. Physiol.,
October 15, 2007;
584(2):
543 - 563.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. A. Thacker, A. K. Clark, F. Marchand, and S. B. McMahon
Pathophysiology of Peripheral Neuropathic Pain: Immune Cells and Molecules
Anesth. Analg.,
September 1, 2007;
105(3):
838 - 847.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. Mizushima, K. Obata, H. Katsura, J. Sakurai, K. Kobayashi, H. Yamanaka, Y. Dai, T. Fukuoka, T. Mashimo, and K. Noguchi
Intensity-Dependent Activation of Extracellular Signal-Regulated Protein Kinase 5 in Sensory Neurons Contributes to Pain Hypersensitivity
J. Pharmacol. Exp. Ther.,
April 1, 2007;
321(1):
28 - 34.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. Kaku, M. Yokoyama, H. Kobayashi, Y. Matsuoka, T. Sato, S. Mizobuchi, Y. Itano, and K. Morita
Altered Response to Formalin by L5 Spinal Nerve Ligation in Rats: A Behavioral and Molecular Study
Anesth. Analg.,
April 1, 2007;
104(4):
936 - 943.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. Obata, H. Katsura, J. Sakurai, K. Kobayashi, H. Yamanaka, Y. Dai, T. Fukuoka, and K. Noguchi
Suppression of the p75 Neurotrophin Receptor in Uninjured Sensory Neurons Reduces Neuropathic Pain after Nerve Injury.
J. Neurosci.,
November 15, 2006;
26(46):
11974 - 11986.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. Katsura, K. Obata, T. Mizushima, J. Sakurai, K. Kobayashi, H. Yamanaka, Y. Dai, T. Fukuoka, M. Sakagami, and K. Noguchi
Activation of SRC-family kinases in spinal microglia contributes to mechanical hypersensitivity after nerve injury.
J. Neurosci.,
August 23, 2006;
26(34):
8680 - 8690.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L Delafoy, A Gelot, D Ardid, A Eschalier, C Bertrand, A M Doherty, and L Diop
Interactive involvement of brain derived neurotrophic factor, nerve growth factor, and calcitonin gene related peptide in colonic hypersensitivity in the rat
Gut,
July 1, 2006;
55(7):
940 - 945.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. M. Garraway, A. J. Anderson, and L. M. Mendell
BDNF-Induced Facilitation of Afferent-Evoked Responses in Lamina II Neurons Is Reduced After Neonatal Spinal Cord Contusion Injury
J Neurophysiol,
September 1, 2005;
94(3):
1798 - 1804.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. D. Wilson-Gerwing, M. V. Dmyterko, D. W. Zochodne, J. M. Johnston, and V. M. K. Verge
Neurotrophin-3 Suppresses Thermal Hyperalgesia Associated with Neuropathic Pain and Attenuates Transient Receptor Potential Vanilloid Receptor-1 Expression in Adult Sensory Neurons
J. Neurosci.,
January 19, 2005;
25(3):
758 - 767.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. M. Ramer, J. F. Borisoff, and M. S. Ramer
Rho-Kinase Inhibition Enhances Axonal Plasticity and Attenuates Cold Hyperalgesia after Dorsal Rhizotomy
J. Neurosci.,
December 1, 2004;
24(48):
10796 - 10805.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. Obata, H. Yamanaka, K. Kobayashi, Y. Dai, T. Mizushima, H. Katsura, T. Fukuoka, A. Tokunaga, and K. Noguchi
Role of Mitogen-Activated Protein Kinase Activation in Injured and Intact Primary Afferent Neurons for Mechanical and Heat Hypersensitivity after Spinal Nerve Ligation
J. Neurosci.,
November 10, 2004;
24(45):
10211 - 10222.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R.-R. Ji and G. Strichartz
Cell Signaling and the Genesis of Neuropathic Pain
Sci. Signal.,
September 28, 2004;
2004(252):
re14 - re14.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. Moriyama, T. Iida, K. Kobayashi, T. Higashi, T. Fukuoka, H. Tsumura, C. Leon, N. Suzuki, K. Inoue, C. Gachet, et al.
Possible Involvement of P2Y2 Metabotropic Receptors in ATP-Induced Transient Receptor Potential Vanilloid Receptor 1-Mediated Thermal Hypersensitivity
J. Neurosci.,
July 9, 2003;
23(14):
6058 - 6062.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. Obata, H. Yamanaka, Y. Dai, T. Tachibana, T. Fukuoka, A. Tokunaga, H. Yoshikawa, and K. Noguchi
Differential Activation of Extracellular Signal-Regulated Protein Kinase in Primary Afferent Neurons Regulates Brain-Derived Neurotrophic Factor Expression after Peripheral Inflammation and Nerve Injury
J. Neurosci.,
May 15, 2003;
23(10):
4117 - 4126.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Schafers, D. H. Lee, D. Brors, T. L. Yaksh, and L. S. Sorkin
Increased Sensitivity of Injured and Adjacent Uninjured Rat Primary Sensory Neurons to Exogenous Tumor Necrosis Factor-alpha after Spinal Nerve Ligation
J. Neurosci.,
April 1, 2003;
23(7):
3028 - 3038.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Ma, Y. Shu, Z. Zheng, Y. Chen, H. Yao, K. W. Greenquist, F. A. White, and R. H. LaMotte
Similar Electrophysiological Changes in Axotomized and Neighboring Intact Dorsal Root Ganglion Neurons
J Neurophysiol,
March 1, 2003;
89(3):
1588 - 1602.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. S. Gold, D. Weinreich, C.-S. Kim, R. Wang, J. Treanor, F. Porreca, and J. Lai
Redistribution of NaV1.8 in Uninjured Axons Enables Neuropathic Pain
J. Neurosci.,
January 1, 2003;
23(1):
158 - 166.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. R. Watkins and S. F. Maier
Beyond Neurons: Evidence That Immune and Glial Cells Contribute to Pathological Pain States
Physiol Rev,
October 1, 2002;
82(4):
981 - 1011.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. Dai, K. Iwata, T. Fukuoka, E. Kondo, A. Tokunaga, H. Yamanaka, T. Tachibana, Y. Liu, and K. Noguchi
Phosphorylation of Extracellular Signal-Regulated Kinase in Primary Afferent Neurons by Noxious Stimuli and Its Involvement in Peripheral Sensitization
J. Neurosci.,
September 1, 2002;
22(17):
7737 - 7745.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|

|