Suppression of the p75 Neurotrophin Receptor in Uninjured Sensory Neurons Reduces Neuropathic Pain after Nerve Injury

• Published in: The Journal of neuroscience 2006-11, Vol.26 (46), p.11974-11986
• Main Authors: Obata, Koichi, Katsura, Hirokazu, Sakurai, Jun, Kobayashi, Kimiko, Yamanaka, Hiroki, Dai, Yi, Fukuoka, Tetsuo, Noguchi, Koichi
• Format: Article
• Language: English
• Subjects: Animals; Axonal Transport - drug effects; Axonal Transport - physiology; Denervation; Disease Models, Animal; Down-Regulation - drug effects; Down-Regulation - physiology; Ganglia, Spinal - drug effects; Ganglia, Spinal - metabolism; Hyperalgesia - drug therapy; Hyperalgesia - metabolism; Hyperalgesia - physiopathology; Ligation; Male; Neuralgia - drug therapy; Neuralgia - metabolism; Neuralgia - physiopathology; Neurons, Afferent - drug effects; Neurons, Afferent - metabolism; p38 Mitogen-Activated Protein Kinases - drug effects; p38 Mitogen-Activated Protein Kinases - metabolism; Peripheral Nervous System Diseases - drug therapy; Peripheral Nervous System Diseases - metabolism; Peripheral Nervous System Diseases - physiopathology; Phosphorylation - drug effects; Rats; Rats, Sprague-Dawley; Receptor, Nerve Growth Factor - antagonists & inhibitors; Receptor, Nerve Growth Factor - metabolism; Receptor, trkA - metabolism; Spinal Nerves - drug effects; Spinal Nerves - injuries; Spinal Nerves - physiopathology; TRPV Cation Channels - drug effects; TRPV Cation Channels - metabolism
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/JNEUROSCI.3188-06.2006

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.