Cellular and Molecular NeuroscienceResearch PaperIntermittent noxious stimulation following spinal cord contusion injury impairs locomotor recovery and reduces spinal brain-derived neurotrophic factor–tropomyosin-receptor kinase signaling in adult rats
Highlights
▶Noxious stimulation after SCI impairs the recovery of locomotor functions. ▶Spinal BDNF and TrkB levels are decreased by noxious stimulation following SCI. ▶Shock engages a neuronal circuitry in the dorsal spinal cord. ▶Impaired locomotor recovery is associated with decreased BDNF-TrkB levels.
Section snippets
Experimental procedures
Male Sprague–Dawley rats obtained from Harlan (Houston, TX, USA) served as subjects. Rats were approximately 90–110 days old and weighed between 350 and 400 g. They were housed individually and maintained on a 12-h light/dark cycle, with all behavioral testing performed during the light cycle. Food and water were available ad libitum. All experiments were carried out in accordance with NIH standards for the care and use of laboratory animals (NIH publications No. 80-23) and were approved by the
Results
Previously, we showed that in adult rats with a complete T2 transection, uncontrollable intermittent shock inhibits adaptive plasticity (Grau et al., 1998) and causes a down-regulation in BDNF mRNA expression within the lumbar spinal cord (Gómez-Pinilla et al., 2007). The same intermittent stimulation also impairs recovery after a contusion injury (Grau et al., 2004). Here, we investigated the cellular pathways that may mediate the detrimental effects of intermittent noxious shock in spinal
Discussion
In several previous studies, we have identified conditions that undermine plasticity or recovery of locomotor functions following SCI. For example, administration of intermittent stimulation to the leg or tail disrupts adaptive plasticity and induces a learning deficit, which lasts up to 48 h in completely transected rats (Crown et al., 2002a). This stimulation paradigm undermines the recovery of locomotor functions in spinal contused rats (Grau et al., 2004). In addition to electrical
Conclusion
This study identifies a potential mechanism for stimulation-induced maladaptive plasticity following SCI. Stimulation that produces a learning deficit significantly decreased components of the BDNF pathway at the lesion site. Although excess BDNF, indicative of peripheral injury or inflammation, can increase BDNF levels beyond normal and consequently lead to central sensitization or pain, following SCI, an increase in spinal BDNF levels can be restorative. On the other end of the spectrum,
Acknowledgments
This work was funded by National Institute of Neurological Disorders and Stroke (NS41548) and National Institute of Child Health and Human Development (HD058412). The authors wish to thank John Hartman for technical assistance and Dr. Kevin Hoy for reviewing an earlier version of this manuscript.
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