BDNF-Induced Plasticity of Spinal Circuits Underlying Pain and Learning

Understanding of the various types of plasticity that occur in the spinal cord, as well as understanding of spinal cord functions, has vastly improved over the past 50 years, mainly due to an increase in the number of research studies and review articles on the subject. It is now understood that the spinal cord is not merely a passive conduit of neural impulses. Instead, the spinal cord can independently execute complex functions. Numerous experimental approaches have been utilized for more targeted exploration of spinal cord functions. For example, isolating the spinal cord from supraspinal influences has been used to demonstrate that simple forms of learning can be performed by spinal neuronal networks. Moreover, reduced preparations, such as acute spinal cord slices, have been used to show that spinal neurons undergo different types of modulation, including activity-dependent synaptic modification. Most spinal cord processes, ranging from integration of incoming sensory input to execution of locomotor outputs, involve plasticity. Nociceptive processing that leads to pain and spinal learning is an example of plasticity that is well-studied in the spinal cord. At the neural level, both processes involve an interplay of cellular mediators, which include glutamate receptors, protein kinases, and growth factors. The neurotrophin brain-derived neurotrophic factor (BDNF) has also been implicated in these processes, specifically as a promoter of both pro-nociception and spinal learning mechanisms. Interestingly, the role of BDNF in mediating spinal plasticity can be altered by injury. The literature spanning approximately 5 decades is reviewed and the role of BDNF is discussed in mediating cellular plasticity underlying pain processing and learning within the spinal cord.