PMID- 12764099 OWN - NLM STAT- MEDLINE DCOM- 20030625 LR - 20220316 IS - 1529-2401 (Electronic) IS - 0270-6474 (Print) IS - 0270-6474 (Linking) VI - 23 IP - 10 DP - 2003 May 15 TI - Differential activation of extracellular signal-regulated protein kinase in primary afferent neurons regulates brain-derived neurotrophic factor expression after peripheral inflammation and nerve injury. PG - 4117-26 AB - To investigate the intracellular signal transduction pathways involved in regulating the gene expression of brain-derived neurotrophic factor (BDNF) in primary afferent neurons, we examined the activation of extracellular signal-regulated protein kinase (ERK) in dorsal root ganglion (DRG) neurons after peripheral inflammation and sciatic nerve transection. Peripheral inflammation induced an increase in the phosphorylation of ERK, mainly in tyrosine kinase A-containing small-to-medium-diameter DRG neurons. The treatment of the mitogen-activated protein kinase (MAPK) kinase 1/2 inhibitor U0126 reversed the pain hypersensitivity and the increase in phosphorylated-ERK (p-ERK) and BDNF in DRG neurons induced by complete Freund's adjuvant. On the other hand, axotomy induced the activation of ERK mainly in medium-and large-sized DRG neurons and in satellite glial cells. U0126 suppressed the axotomy-induced autotomy behavior and reversed the increase in p-ERK and BDNF. The intrathecal application of nerve growth factor (NGF) induced an increase in the number of p-ERK-and BDNF-labeled cells, mainly small neurons, and the application of anti-NGF induced an increase in p-ERK and BDNF in some medium-to-large-diameter DRG neurons. The activation of MAPK in the primary afferents may occur in different populations of DRG neurons after peripheral inflammation and axotomy, respectively, through alterations in the target-derived NGF. These changes, including the changes in BDNF expression, might be involved in the pathophysiological changes in primary afferent neurons. FAU - Obata, Koichi AU - Obata K AD - Department of Anatomy and Neuroscience, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan. FAU - Yamanaka, Hiroki AU - Yamanaka H FAU - Dai, Yi AU - Dai Y FAU - Tachibana, Toshiya AU - Tachibana T FAU - Fukuoka, Tetsuo AU - Fukuoka T FAU - Tokunaga, Atsushi AU - Tokunaga A FAU - Yoshikawa, Hideki AU - Yoshikawa H FAU - Noguchi, Koichi AU - Noguchi K LA - eng 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 (Activating Transcription Factor 3) RN - 0 (Atf3 protein, rat) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Butadienes) RN - 0 (Enzyme Inhibitors) RN - 0 (Glial Fibrillary Acidic Protein) RN - 0 (Neurofilament Proteins) RN - 0 (Nitriles) RN - 0 (Transcription Factors) RN - 0 (U 0126) RN - 108688-71-7 (neurofilament protein H) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) SB - IM MH - Activating Transcription Factor 3 MH - Animals MH - Axotomy MH - Behavior, Animal/drug effects/physiology MH - Brain-Derived Neurotrophic Factor/*biosynthesis/genetics/immunology MH - Butadienes/pharmacology MH - Enzyme Activation/physiology MH - Enzyme Inhibitors/pharmacology MH - Ganglia, Spinal/*enzymology/injuries/metabolism MH - Gene Expression Regulation/drug effects/physiology MH - Glial Fibrillary Acidic Protein/metabolism MH - Immunohistochemistry MH - Inflammation/enzymology/physiopathology MH - Injections, Spinal MH - Male MH - Mitogen-Activated Protein Kinases/*metabolism/physiology MH - Neurofilament Proteins/metabolism MH - Neuroglia/drug effects/enzymology/metabolism/pathology MH - Neurons, Afferent/chemistry/*enzymology/metabolism/pathology MH - Nitriles/pharmacology MH - Pain Threshold/drug effects MH - Phosphorylation/drug effects MH - Rats MH - Rats, Sprague-Dawley MH - Sciatic Nerve/enzymology/*injuries/*pathology MH - Transcription Factors/metabolism PMC - PMC6741084 EDAT- 2003/05/24 05:00 MHDA- 2003/06/26 05:00 PMCR- 2003/11/15 CRDT- 2003/05/24 05:00 PHST- 2003/05/24 05:00 [pubmed] PHST- 2003/06/26 05:00 [medline] PHST- 2003/05/24 05:00 [entrez] PHST- 2003/11/15 00:00 [pmc-release] AID - 23/10/4117 [pii] AID - 10.1523/JNEUROSCI.23-10-04117.2003 [doi] PST - ppublish SO - J Neurosci. 2003 May 15;23(10):4117-26. doi: 10.1523/JNEUROSCI.23-10-04117.2003.