Brain-derived neurotrophic factor modulates nociceptive sensory inputs andNMDA-evoked responses in the rat spinal cord

Central sensitization, the hyperexcitability of spinal processing that ofte n accompanies peripheral injury, is a major component of many persistent pa in states. Here we report that the neurotrophin, brain-derived neurotrophic factor (BDNF), is a modulator of excitability within the spinal cord and c ontributes to the mechanism of central sensitization. BDNF, localized in pr imary sensory neuron cell bodies and central terminals, potentiates nocicep tive spinal reflex responses in an in vitro spinal cord preparation and ind uces c-fos expression in dorsal horn neurons. NMDA receptor-mediated respon ses, known as a major contributor to central sensitization, were significan tly enhanced by exogenous BDNF. Systemic NGF treatment, a procedure that mi mics peripheral inflammatory states, raises BDNF levels in sensory neurons and increases nociceptive spinal reflex excitability. This increased centra l excitability is reduced by trkB-IgG, a BDNF "antagonist." We also show di rectly that inflammatory pain-related behavior depends on BDNF release in v ivo. Thus behavioral nociceptive responses induced by intraplantar formalin and by intraplantar carageenan are significantly attenuated by trkB-IgG. H ence BDNF is appropriately localized and regulated in inflammatory states a nd is sufficient and necessary for the expression of central sensitization in the spinal cord. We propose that BDNF may function as a modulator of cen tral sensitization in pathological states, and our results suggest that pha rmacological antagonism of BDNF may prove an effective and novel analgesic strategy for the treatment of persistent inflammatory pain states.