PMID- 10393886 OWN - NLM STAT- MEDLINE DCOM- 19990826 LR - 20190501 IS - 0027-8424 (Print) IS - 1091-6490 (Electronic) IS - 0027-8424 (Linking) VI - 96 IP - 14 DP - 1999 Jul 6 TI - Brain-derived neurotrophic factor is an endogenous modulator of nociceptive responses in the spinal cord. PG - 7714-8 AB - The primary sensory neurons that respond to noxious stimulation and project to the spinal cord are known to fall into two distinct groups: one sensitive to nerve growth factor and the other sensitive to glial cell-line-derived neurotrophic factor. There is currently considerable interest in the ways in which these factors may regulate nociceptor properties. Recently, however, it has emerged that another trophic factor-brain-derived neurotrophic factor (BDNF)-may play an important neuromodulatory role in the dorsal horn of the spinal cord. BDNF meets many of the criteria necessary to establish it as a neurotransmitter/neuromodulator in small-diameter nociceptive neurons. It is synthesized by these neurons and packaged in dense core vesicles in nociceptor terminals in the superficial dorsal horn. It is markedly up-regulated in inflammatory conditions in a nerve growth factor-dependent fashion. Postsynaptic cells in this region express receptors for BDNF. Spinal neurons show increased excitability to nociceptive inputs after treatment with exogenous BDNF. There are both electrophysiological and behavioral data showing that antagonism of BDNF at least partially prevents some aspects of central sensitization. Together, these findings suggest that BDNF may be released from primary sensory nociceptors with activity, particularly in some persistent pain states, and may then increase the excitability of rostrally projecting second-order systems. BDNF released from nociceptive terminals may thus contribute to the sensory abnormalities associated with some pathophysiological states, notably inflammatory conditions. FAU - Thompson, S W AU - Thompson SW AD - Division of Physiology, Sherrington Building, St. Thomas' Hospital Campus, Lambeth Palace Road, London SE1 7EH, United Kingdom. FAU - Bennett, D L AU - Bennett DL FAU - Kerr, B J AU - Kerr BJ FAU - Bradbury, E J AU - Bradbury EJ FAU - McMahon, S B AU - McMahon SB LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Review PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (Brain-Derived Neurotrophic Factor) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/*physiology MH - Humans MH - Models, Neurological MH - Neurons, Afferent/physiology MH - Nociceptors/*physiology MH - Pain/*physiopathology MH - Spinal Cord/*physiology/physiopathology PMC - PMC33607 EDAT- 1999/07/08 00:00 MHDA- 1999/07/08 00:01 PMCR- 2000/01/06 CRDT- 1999/07/08 00:00 PHST- 1999/07/08 00:00 [pubmed] PHST- 1999/07/08 00:01 [medline] PHST- 1999/07/08 00:00 [entrez] PHST- 2000/01/06 00:00 [pmc-release] AID - 1735 [pii] AID - 10.1073/pnas.96.14.7714 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 1999 Jul 6;96(14):7714-8. doi: 10.1073/pnas.96.14.7714.