For nearly two decades, much research has focused on brain-derived neurotrophic factor (BDNF), an important member of the neurotrophin family. Results from these studies show that BDNF exerts numerous modulatory actions within the central nervous system; actions ranging from cellular and molecular to behavioral. In the spinal cord, BDNF is identified as a critical mediator of central sensitization and spinal nociception that underlie the development of pain hypersensitivity. In addition to these actions, BDNF has also been implicated in beneficial effects such as promoting functional recovery following spinal cord injury (SCI). The existence of both adaptive and maladaptive spinal effects of BDNF has led us to propose that BDNF functions in a state dependent manner; that its specific actions are determined by whether or not a SCI exists. To affirm this proposal, we conducted studies that utilized several experimental designs to investigate the effects of BDNF on spinal plasticity in naïve and spinal cord injured subjects. In the first set of studies, we used spinal cord slices in juvenile rats to examine the effect of exogenously administered BDNF on dorsal root-evoked synaptic currents in lamina II neurons. The results showed that in naïve subjects, BDNF produces a prolonged synaptic facilitation that requires post-synaptic NMDA receptors, protein kinase C and increases in intracellular calcium, indicating a pro-nociceptive role for BDNF. However, BDNF fails to induce facilitation of the evoked synaptic responses in the injured spinal cord. The second set of experiments used a simple instrumental learning paradigm to assess the interaction between controllable shock and BDNF in adult rats with a complete spinal transection. Previous studies had shown that controllable shock to the hindlimb promotes adaptive plasticity and facilitates subsequent spinal learning through BDNF-dependent mechanisms (Gómez-Pinilla et al., 2007; Neuroscience 148:893-906). Supporting this, we demonstrated that controllable shock significantly increases the expression of BDNF and its receptor, TrkB, primarily in the spinal dorsal horn. Our third set of experiments assessed the relationship between spinal BDNF levels and the detrimental effects of intermittent nociceptive stimulation (~0.5Hz) in adult subjects with a moderate contusion injury. Previous observations showed that this stimulation paradigm induces a learning deficit and undermines functional recovery following SCI (Crown et al., 2002; Behav. Neurosci. 116:1032-1051). We now show that noxious stimulation shortly after SCI significantly increases the onset and maintenance of mechanical allodynia in adult rats with a moderate spinal cord contusion injury. Surprisingly, this pro-nociceptive response is accompanied by a decrease in the spinal expression of BDNF, TrkB and associated downstream signaling kinases, ERK1/2 and CAMKII. Together, these observations suggest that injury alters how BDNF affects spinal nociceptive processing. In the absence of SCI, BDNF promotes central sensitization and spinal nociception. In contrast, after injury BDNF appears to have a protective effect that attenuates the effect of nociceptive stimulation.