BDNF modulates sensory neuron synaptic activity by a facilitation of GABA transmission in the dorsal horn.
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.
D000344:Afferent Pathways / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism / Q000494:pharmacology*; D002478:Cells, Cultured; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000378:metabolism; D007278:Injections, Spinal; D008297:Male; D009292:Narcotic Antagonists / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D020671:Posterior Horn Cells / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D011957:Receptors, Opioid / Q000378:metabolism; D013373:Substance P / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism* / Q000494:pharmacology
D019208:Brain-Derived Neurotrophic Factor; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D013373:Substance P; D005680:gamma-Aminobutyric Acid