PMID- 12359151 OWN - NLM STAT- MEDLINE DCOM- 20021119 LR - 20191106 IS - 1044-7431 (Print) IS - 1044-7431 (Linking) VI - 21 IP - 1 DP - 2002 Sep TI - BDNF modulates sensory neuron synaptic activity by a facilitation of GABA transmission in the dorsal horn. PG - 51-62 AB - Topical application of brain-derived neurotrophic factor (BDNF) to the adult rat isolated dorsal horn with dorsal root attached preparation inhibited the electrically evoked release of substance P (SP) from sensory neurons. This effect of BDNF was dose dependent (EC(50) 250 pM) and reversed by the tyrosine kinase inhibitor, K-252a. BDNF-induced inhibition of SP release was blocked by the GABA(B) receptor antagonist CGP 55485 but not by naloxone. Acute application of BDNF significantly increased potassium-stimulated release of GABA in the dorsal horn isolated in vitro and this effect was blocked by K-252a. Intrathecal injection of BDNF into the rat lumbar spinal cord induced a short-lasting increase in hindpaw threshold to noxious thermal stimulation that was blocked by CGP 55485 and was associated with activation of ERK in dorsal horn. These data suggest that exogenous BDNF can indirectly modulate primary sensory neuron synaptic efficacy via facilitation of the release of GABA from dorsal horn interneurons. FAU - Pezet, Sophie AU - Pezet S AD - Neuroscience Research Centre, Guy's, King's and St Thomas' School of Biomedical Sciences, King's College London, London SE1 1UL, United Kingdom. FAU - Cunningham, Joanna AU - Cunningham J FAU - Patel, Jaykumar AU - Patel J FAU - Grist, John AU - Grist J FAU - Gavazzi, Isabella AU - Gavazzi I FAU - Lever, Isobel J AU - Lever IJ FAU - Malcangio, Marzia AU - Malcangio M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Mol Cell Neurosci JT - Molecular and cellular neurosciences JID - 9100095 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Narcotic Antagonists) RN - 0 (Receptors, Opioid) RN - 33507-63-0 (Substance P) RN - 56-12-2 (gamma-Aminobutyric Acid) SB - IM MH - Afferent Pathways/*drug effects/metabolism MH - Animals MH - Brain-Derived Neurotrophic Factor/metabolism/*pharmacology MH - Cells, Cultured MH - Ganglia, Spinal/*drug effects/metabolism MH - Injections, Spinal MH - Male MH - Narcotic Antagonists/pharmacology MH - Neural Inhibition/drug effects/physiology MH - Pain/*drug therapy/metabolism/physiopathology MH - Pain Threshold/drug effects/physiology MH - Posterior Horn Cells/*drug effects/metabolism MH - Rats MH - Rats, Wistar MH - Reaction Time/drug effects/physiology MH - Receptors, Opioid/metabolism MH - Substance P/metabolism MH - Synaptic Transmission/*drug effects/physiology MH - gamma-Aminobutyric Acid/*metabolism/pharmacology EDAT- 2002/10/03 04:00 MHDA- 2002/11/26 04:00 CRDT- 2002/10/03 04:00 PHST- 2002/10/03 04:00 [pubmed] PHST- 2002/11/26 04:00 [medline] PHST- 2002/10/03 04:00 [entrez] AID - S1044743102911668 [pii] AID - 10.1006/mcne.2002.1166 [doi] PST - ppublish SO - Mol Cell Neurosci. 2002 Sep;21(1):51-62. doi: 10.1006/mcne.2002.1166.