BDNF: a neuromodulator in nociceptive pathways?

During development, brain-derived neurotrophic factor (BDNF) supports the survival of certain neuronal population in central and peripheral nervous system. In adulthood, BDNF has been suggested to act as an important modulator of synaptic plasticity. This article reviews and discusses its potential role as neuromodulator in the spinal dorsal horn. BDNF is synthesized in the cell body of primary sensory neurons (pre-synaptic neurons) and its expression is regulated in models of inflammatory and neuropathic pain. The high affinity receptor for BDNF, tropomyosine receptor kinase B (TrkB), is expressed by post-synaptic neurons of the dorsal horn. Stimulation of pre-synaptic nociceptive afferent fibres induces BDNF release and consequent activation of TrkB receptors leading to a post-synaptic excitability. Electrophysiological recordings showed that BDNF enhances the ventral root potential induced by C-fibre stimulation in an in vitro preparation. In addition, behavioural data indicate that antagonism of BDNF attenuates the second phase of hyperalgesia induced by formalin (in nerve growth factor-treated animals) and the thermal hyperalgesia induced by carageenan, suggesting that BDNF is involved in some aspects of central sensitisation in conditions of peripheral inflammation. In conclusion, BDNF meets many of the criteria necessary to define it as a neurotransmitter/neuromodulator in small diameter nociceptive neurons.