Brain-derived neurotrophic factor is an endogenous modulator of nociceptive responses in the spinal cord

The primary sensory neurons that respond to noxious stimulation and project to the spinal cord are known to fall into two distinct groups: one sensiti ve to nerve growth factor and the other sensitive to glial cell-line-derive d neurotrophic factor. There is currently considerable interest in the ways in which these factors may regulate nociceptor properties. Recently, howev er, it has emerged that another trophic factor-brain-derived neurotrophic f actor (BDNF)-may play an important neuromodulatory role in the dorsal born of the spinal cord. BDNF meets many of the criteria necessary to establish it as a neurotransmitter/neuromodulator in small-diameter nociceptive neuro ns. It is synthesized by these neurons and packaged in dense core vesicles in nociceptor terminals in the superficial dorsal horn. It is markedly up-r egulated in inflammatory conditions in a nerve growth factor-dependent fash ion. Postsynaptic cells in this region express receptors for BDNF. Spinal n eurons show increased excitability to nociceptive inputs after treatment wi th exogenous BDNF. There are both electrophysiological and behavioral data showing that antagonism of BDNF at least partially prevents some aspects of central sensitization. Together, these findings suggest that BDNF may be r eleased from primary sensory nociceptors with activity, particularly in som e persistent pain states, and may then increase the excitability of rostral ly projecting second-order systems. BDNF released from nociceptive terminal s may thus contribute to the sensory abnormalities associated with some pat hophysiological states, notably inflammatory conditions.