Brain-derived neurotrophic factor-elicited or sciatic ligation-associated phosphorylation of cyclic AMP response element binding protein in the rat spinal dorsal horn is reduced by block of tyrosine kinase receptors

Brain-derived neurotrophic factor (BDNF) and cyclic AMP response element binding protein (CREB) may critically contribute to injury-associated plasticity and thus to the development of persistent pain. In the present study we examined the potential interaction between CREB and BDNF in the spinal dorsal horn. Significant CREB phosphorylation was elicited by local application of BDNF (1 μg) onto the spinal dorsal horn of control, uninjured animals. The degree of phosphorylation was similar to that elicited by loose ligation of the sciatic nerve. The tyrosine kinase (Trk) blocker K252a (2 μg) significantly reduced the CREB phosphorylation elicited either by BDNF or the sciatic ligation. These data provided further support for the notion that at least some of the injury-associated activation of CREB in the spinal dorsal horn may be dependent upon BDNF-mediated activation of Trk receptors.