Suppression of the p75 neurotrophin receptor in uninjured sensory neurons reduces neuropathic pain after nerve injury.
The p75 neurotrophin receptor (p75NTR) has been implicated in diverse neuronal responses, including survival, cell death, myelination, and inhibition of regeneration. However, the role of p75NTR in neuropathic pain, for which there is currently no effective therapy, has not been explored. Here, we report that the pharmacological blockade of p75NTR in primary sensory neurons reversed neuropathic pain after nerve injury. Nerve injury increased the expression and axonal transport of p75NTR and phosphorylation of TrkA in the uninjured primary afferents. Functional inhibition of p75NTR suppressed injury-induced neuropathic pain and decreased the phosphorylation of TrkA and p38 mitogen-activated protein kinase, and the induction of transient receptor potential channels in dorsal root ganglion (DRG) neurons. Our results show that p75NTR induced in undamaged DRG neurons facilitates TrkA signaling and contributes to heat and cold hyperalgesia.
Obata
Koichi
K
Department of Anatomy and Neuroscience, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
Katsura
Hirokazu
H
Sakurai
Jun
J
Kobayashi
Kimiko
K
Yamanaka
Hiroki
H
Dai
Yi
Y
Fukuoka
Tetsuo
T
Noguchi
Koichi
K
D000818:Animals; D001370:Axonal Transport / Q000187:drug effects / Q000502:physiology; D003714:Denervation; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D006930:Hyperalgesia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008026:Ligation; D008297:Male; D009437:Neuralgia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009475:Neurons, Afferent / Q000187:drug effects* / Q000378:metabolism; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D020800:Receptor, Nerve Growth Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020917:Receptor, trkA / Q000378:metabolism; D013127:Spinal Nerves / Q000187:drug effects* / Q000293:injuries / Q000503:physiopathology; D050916:TRPV Cation Channels / Q000187:drug effects / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism
D020800:Receptor, Nerve Growth Factor; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat; D020917:Receptor, trkA; D048051:p38 Mitogen-Activated Protein Kinases