Actions of brain-derived neurotrophic factor on spinal nociceptive transmission during inflammation in the rat.
The aim of the current study was to investigate whether, and if so how, brain-derived neurotrophic factor (BDNF) acts to develop the spinal sensitization underlying inflammation-induced hyperalgesia. In spinal cord slice preparations from rats with inflammation induced by complete Freund's adjuvant (CFA), BDNF, but not nerve growth factor (NGF) or neurotrophin-3 (NT-3), acted presynaptically to increase the frequency of excitatory miniature EPSCs in substantia gelatinosa (SG) neurones of the CFA-treated, but not untreated rats, through activation of lidocaine (lignocaine)-sensitive, TTX-resistant Na+ channels. This effect was observed in the spinal cord slices of the CFA-treated rat only 2-4 days after the CFA injection. On the other hand, the number of monosynaptic Abeta afferent inputs to the SG significantly increased 1 week after the onset of the inflammation, and this increase was significantly suppressed by treatment with anti-BDNF antiserum administered 1 day before and just after the CFA injection. In addition, the treatment with anti-BDNF antiserum significantly attenuated the CFA-induced hyperalgesia and/or allodynia. These findings, taken together, suggest that BDNF, which is considered to be released from the sensitized primary afferents, increases the excitability of SG neurones through its action on the presynaptic terminals. BDNF may thereafter induce monosynaptic Abeta afferents to the SG, thereby developing hyperalgesia and/or allodynia during inflammation.
Matayoshi
Satoru
S
Department of Integrative Physiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
Jiang
Nan
N
Katafuchi
Toshihiko
T
Koga
Kohei
K
Furue
Hidemasa
H
Yasaka
Toshiharu
T
Nakatsuka
Terumasa
T
Zhou
Xin-Fu
XF
Kawasaki
Yasuhiko
Y
Tanaka
Nobuyuki
N
Yoshimura
Megumu
M
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000276:immunology / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005620:Freund's Adjuvant; D005727:Ganglia, Spinal / Q000502:physiology; D006930:Hyperalgesia / Q000188:drug therapy / Q000503:physiopathology*; D007116:Immunization, Passive; D066298:In Vitro Techniques; D008297:Male; D009187:Myelitis / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D009414:Nerve Growth Factors / Q000502:physiology; D009475:Neurons, Afferent / Q000502:physiology; D020933:Neurotrophin 3 / Q000502:physiology; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000502:physiology; D015222:Sodium Channels / Q000502:physiology; D013116:Spinal Cord / Q000503:physiopathology*; D013376:Substantia Gelatinosa / Q000503:physiopathology; D009435:Synaptic Transmission / Q000502:physiology*; D013997:Time Factors
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D015222:Sodium Channels; D005620:Freund's Adjuvant; D020813:Receptor, trkB