PMID- 11404434 OWN - NLM STAT- MEDLINE DCOM- 20010712 LR - 20240420 IS - 1529-2401 (Electronic) IS - 0270-6474 (Print) IS - 0270-6474 (Linking) VI - 21 IP - 12 DP - 2001 Jun 15 TI - Brain-derived neurotrophic factor is released in the dorsal horn by distinctive patterns of afferent fiber stimulation. PG - 4469-77 AB - Brain-derived neurotrophic factor (BDNF) is synthesized by small neuron cell bodies in the dorsal root ganglia (DRG) and is anterogradely transported to primary afferent terminals in the dorsal horn where it is involved in the modulation of painful stimuli. Here we show that BDNF is released in the rat isolated dorsal horn after chemical stimulation by capsaicin or electrical stimulation of dorsal roots. Capsaicin superfusion (1-100 microm) 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. BDNF release was also seen after electrical stimulation of the dorsal roots at C-fiber strength. This release was encoded by specific patterns of afferent fiber stimulation. Neither continuous low-frequency (480 pulses, 1 Hz) nor tetanic high-frequency (300 pulses in 3 trains, 100 Hz) stimulation evoked release of BDNF, although substance P (SP) release was observed under both of these conditions. However, BDNF was released after short bursts of high-frequency stimulation (300 pulses in 75 trains, 100 Hz) along with SP and glutamate. The NMDA antagonist d-AP-5 inhibited electrically evoked BDNF release. BDNF release was also measured after systemic or intrathecal NGF treatment. This upregulated BDNF content in the DRG and increased the capsaicin-evoked release of BDNF. Similarly, the amount of BDNF released by burst stimulation was increased after NGF treatment. This activity-dependent release continued to be encoded solely by this stimulation pattern. These experiments demonstrate that BDNF release in the dorsal horn is encoded by specific patterns of afferent fiber stimulation and is mediated by NMDA receptor activation. FAU - Lever, I J AU - Lever IJ AD - Neuroscience Research Center and Department of Pharmacology, Guy's, King's, and St. Thomas' School of Biomedical Sciences, King's College London, London SE1 1UL, United Kingdom. FAU - Bradbury, E J AU - Bradbury EJ FAU - Cunningham, J R AU - Cunningham JR FAU - Adelson, D W AU - Adelson DW FAU - Jones, M G AU - Jones MG FAU - McMahon, S B AU - McMahon SB FAU - Marvizon, J C AU - Marvizon JC FAU - Malcangio, M AU - Malcangio M LA - eng GR - WT_/Wellcome Trust/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Excitatory Amino Acid Antagonists) RN - 0 (Receptors, N-Methyl-D-Aspartate) RN - 33507-63-0 (Substance P) RN - 3KX376GY7L (Glutamic Acid) RN - 9061-61-4 (Nerve Growth Factor) RN - S07O44R1ZM (Capsaicin) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Capsaicin/pharmacology MH - Dose-Response Relationship, Drug MH - Electric Stimulation/methods MH - Enzyme-Linked Immunosorbent Assay MH - Excitatory Amino Acid Antagonists/pharmacology MH - Glutamic Acid/metabolism MH - In Vitro Techniques MH - Male MH - Nerve Growth Factor/pharmacology MH - Neurons, Afferent/*physiology MH - Posterior Horn Cells/drug effects/metabolism MH - Rats MH - Rats, Wistar MH - Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors MH - Spinal Cord/drug effects/*metabolism MH - Spinal Nerve Roots/physiology MH - Stimulation, Chemical MH - Substance P/metabolism PMC - PMC6762751 EDAT- 2001/06/16 10:00 MHDA- 2001/07/13 10:01 PMCR- 2001/12/15 CRDT- 2001/06/16 10:00 PHST- 2001/06/16 10:00 [pubmed] PHST- 2001/07/13 10:01 [medline] PHST- 2001/06/16 10:00 [entrez] PHST- 2001/12/15 00:00 [pmc-release] AID - 21/12/4469 [pii] AID - 5310 [pii] AID - 10.1523/JNEUROSCI.21-12-04469.2001 [doi] PST - ppublish SO - J Neurosci. 2001 Jun 15;21(12):4469-77. doi: 10.1523/JNEUROSCI.21-12-04469.2001.