Spinal Plasticity and Behavior: BDNF-Induced Neuromodulation in Uninjured and Injured Spinal Cord

Abstract

Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophic factor family of signaling molecules. Since its discovery over three decades ago, BDNF has been identified as an important regulator of neuronal development, synaptic transmission, and cellular and synaptic plasticity and has been shown to function in the formation and maintenance of certain forms of memory. Neural plasticity that underlies learning and memory in the hippocampus shares distinct characteristics with spinal cord nociceptive plasticity. Research examining the role BDNF plays in spinal nociception and pain overwhelmingly suggests that BDNF promotes pronociceptive effects. BDNF induces synaptic facilitation and engages central sensitization-like mechanisms. Also, peripheral injury-induced neuropathic pain is often accompanied with increased spinal expression of BDNF. Research has extended to examine how spinal cord injury (SCI) influences BDNF plasticity and the effects BDNF has on sensory and motor functions after SCI. Functional recovery and adaptive plasticity after SCI are typically associated with upregulation of BDNF. Although neuropathic pain is a common consequence of SCI, the relation between BDNF and pain after SCI remains elusive. This article reviews recent literature and discusses the diverse actions of BDNF. We also highlight similarities and differences in BDNF-induced nociceptive plasticity in naïve and SCI conditions.

Cross-talk signaling in the trigeminal ganglion: role of neuropeptides and other mediators

“…2). BDNF can be released from central presynaptic terminals and may act on pre-and postsynaptic tyrosine kinase (TrkB) receptors to facilitate nociceptive transmission (Garraway and Huie 2016).…”

Targeting Neurotrophins to Specific Populations of Neurons: NGF, BDNF, and NT-3 and Their Relevance for Treatment of Spinal Cord Injury

“…Some authors found reversal of allodynia with BDNF treatment [131,132,133], or that pronociceptive effects may only occur in the non-injured state [134]. There is also speculation that BDNF’s contribution to spasticity may only be induced by continuously high levels of this factor, and thus a regulated or transient dosage may solve this potential problem [135].…”

AMPAkines and morphine provide complementary analgesia

“…BDNF plays a key role in synaptic plasticity, and its increase may be responsible for some of the analgesic effects seen with AMPAkine treatment in our study. BDNF is also expressed in the spinal dorsal horn, where it can have a pro-nociceptive effect [35–37]. It is possible that there is a balance between pro- and anti-nocicpetive effects mediated by BDNF signaling.…”