BDNF sensitizes the response of lamina II neurons to high threshold primary afferent inputs

SM Garraway, JC Petruska… - European Journal of …, 2003 - Wiley Online Library
SM Garraway, JC Petruska, LM Mendell
European Journal of Neuroscience, 2003Wiley Online Library
Brain‐derived neurotrophic factor (BDNF) is up‐regulated and released in the dorsal horn
following peripheral inflammation and has therefore been implicated in spinal mechanisms
of sensitization. Despite these observations, the mechanisms associated with such a role for
BDNF are not yet fully determined. Here, we investigate the effect of BDNF on dorsal root‐
evoked synaptic transmission in lamina II neurons. In a transverse spinal cord slice
preparation from neonatal rats (P1–15), the whole cell patch‐clamp technique was used to …
Abstract
Brain‐derived neurotrophic factor (BDNF) is up‐regulated and released in the dorsal horn following peripheral inflammation and has therefore been implicated in spinal mechanisms of sensitization. Despite these observations, the mechanisms associated with such a role for BDNF are not yet fully determined. Here, we investigate the effect of BDNF on dorsal root‐evoked synaptic transmission in lamina II neurons. In a transverse spinal cord slice preparation from neonatal rats (P1–15), the whole cell patch‐clamp technique was used to record from these neurons. Brief application of BDNF (50–200 ng/mL) facilitated the evoked synaptic currents; they remained enhanced even after BDNF was washed out. A significant minority of cells was minimally affected by BDNF and consistent with this, not all neurons in lamina II were immunoreactive for the tyrosine kinase (trk) B receptor. No facilitation was elicited when N‐methyl‐d‐aspartate (NMDA) receptors were blocked with D‐APV, when the postsynaptic NMDA receptors were selectively blocked with intracellular MK‐801, or when postsynaptic neurons were loaded with BAPTA. Additionally, inhibiting phospholipase C (PLC) or protein kinase C (PKC) prior to BDNF application completely blocked facilitation. However, once synaptic current underwent BDNF‐induced facilitation, the PKC inhibitors failed to reverse the effect, suggesting that PKC is needed for initiation, but not maintenance of BDNF‐induced facilitation. These results demonstrate that BDNF functions at the spinal level to enhance synaptic efficacy in an NMDA receptor‐dependent manner and requires the action of the PLC/PKC pathway. This action of BDNF may contribute to central sensitization and exaggerated pain states.
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