Brain-derived neurotrophic factor is released in the dorsal horn by distinctive patterns of afferent fiber stimulation

Brain-derived neurotrophic factor (BDNF) is synthesized by small neuron cel l bodies in the dorsal root ganglia (DRG) and is anterogradely transported to primary afferent terminals in the dorsal horn where it is involved in th e modulation of painful stimuli. Here we show that BDNF is released in the rat isolated dorsal horn after chemical stimulation by capsaicin or electri cal stimulation of dorsal roots. Capsaicin superfusion (1-100 muM) induced a dose-dependent release of BDNF, measured using ELISA. The highest dose of capsaicin also induced a depletion of BDNF protein in the dorsal horn. BDN F release was also seen after electrical stimulation of the dorsal roots at C-fiber strength. This release was encoded by specific patterns of afferen t fiber stimulation. Neither continuous low-frequency (480 pulses, 1 Hz) no r tetanic high-frequency (300 pulses in 3 trains, 100 Hz) stimulation evoke d release of BDNF, although substance P (SP) release was observed under bot h of these conditions. However, BDNF was released after short bursts of hig h-frequency stimulation (300 pulses in 75 trains, 100 Hz) along with SP and glutamate. The NMDA antagonist D-AP-5 inhibited electrically evoked BDNF r elease. BDNF release was also measured after systemic or intrathecal NGF tr eatment. This upregulated BDNF content in the DRG and increased the capsaic in-evoked release of BDNF. Similarly, the amount of BDNF released by burst stimulation was increased after NGF treatment. This activity-dependent rele ase continued to be encoded solely by this stimulation pattern. These exper iments demonstrate that BDNF release in the dorsal horn is encoded by speci fic patterns of afferent fiber stimulation and is mediated by NMDA receptor activation.