• Jing Zhao, Anjan Seereeram, Mohammed A Nassar, Alessandra Levato, Sophie Pezet, Gareth Hathaway, Cruz Morenilla-Palao, Caroline Stirling, Maria Fitzgerald, Stephen B McMahon, Maribel Rios, John N Wood, and London Pain Consortium.
• Molecular Nociception Group, Department of Biology, University College London, London WC1E 6BT, UK.
• Mol. Cell. Neurosci. 2006 Mar 1;31(3):539-48.

AbstractConditional mouse knock-outs provide an informative approach to drug target validation where no pharmacological blockers exist or global knock-outs are lethal. Here, we used the Cre-loxP system to delete BDNF in most nociceptive sensory neurons. Conditional null animals were healthy with no sensory neuron loss. However, pain-related behavior was substantially altered. Baseline thermal thresholds were reduced. Carrageenan-induced thermal hyperalgesia was inhibited. Formalin-induced pain behavior was attenuated in the second phase, and this correlated with abolition of NMDA receptor NR1 Ser896/897 phosphorylation and ERK1 and ERK2 activation in the dorsal horn; AMPA receptor phosphorylation (GluR1/Ser831) was unaffected. NGF-induced thermal hyperalgesia was halved, and mechanical secondary hyperalgesia caused by intramuscular NGF was abolished. By contrast, neuropathic pain behavior developed normally. Nociceptor-derived BDNF thus plays an important role in regulating inflammatory pain thresholds and secondary hyperalgesia, but BDNF released only from nociceptors plays no role in the development of neuropathic pain.

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