Intermittent nociceptive stimulation following a complete transection or contused spinal cord injury (SCI) has been shown to exert several short and long lasting negative consequences. These include maladaptive spinal plasticity, enhanced mechanical allodynia and impaired functional recovery of locomotor and bladder functions. The neurotrophin, brain derived neurotrophic factor (BDNF) has been shown to play an important role in adaptive plasticity and also to restore functions following SCI. This suggests that the negative behavioral effects of shock are most likely related to corresponding changes in BDNF spinal levels. In this study we investigated the cellular effects of nociceptive stimulation in contused adult rats focusing on BDNF, its receptor, TrkB, and the subsequent downstream signaling system. The goal was to determine whether the behavioral effect of stimulation is associated with concomitant cellular changes induced during the initial post-injury period. Quantitative RT-PCR and western blotting were used to assess changes in the mRNA and/or protein levels of BDNF, TrkB and the downstream signaling proteins CAMKII and ERK1/2 at 1 hour, 24 hours and 7 days following administration of intermittent noxious shock to the tail of contused subjects. In addition, recovery of locomotor function (BBB score) was assessed daily for the first week post injury. The results showed that, while nociceptive stimulation failed to induce any changes in gene expression at 1 hour, it significantly reduced the expression of BDNF, TrkB, ERK2 and CAMKII, at 24 hours. In general, changes in gene expression were spatially localized to the dorsal spinal cord. In addition, locomotor recovery was impaired by shock. Evidence is also provided suggesting that shock engages a neuronal circuitry without having any negative effects on neuronal survival at 24 hours. These results suggest that nociceptive activity following SCI decreases BDNF and TrkB levels, which may significantly contribute to diminished functional recovery.

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