title: Nerve growth factor-induced synapse-like structures in contralateral sensory ganglia contribute to chronic mirror-image pain.
abstract: Elevated nerve growth factor (NGF) in the contralateral dorsal root ganglion (DRG) mediates mirror-image pain after peripheral nerve injury, but the underlying mechanism remains unclear. Using intrathecal injection of NGF antibodies, we found that NGF is required for the development of intra-DRG synapse-like structures made by neurite sprouts of calcitonin gene-related peptide (CGRP(+)) nociceptors and sympathetic axons onto neurite sprouts of Kv4.3(+) nociceptors. These synapse-like structures are formed near NGF-releasing satellite glia surrounding large DRG neurons. Downregulation of the postsynaptic protein PSD95 with a specific shRNA largely eliminates these synapse-like structures, suppresses activities of Kv4.3(+) but not CGRP(+) nociceptors, and attenuates mirror-image pain. Furthermore, neutralizing the neurotransmitter norepinephrine or CGRP in the synapse-like structures by antibodies has similar analgesic effect. Thus, elevated NGF after peripheral nerve injury induces neurite sprouting and the formation of synapse-like structures within the contralateral DRG, leading to the development of chronic mirror-image pain.
authors.affiliation: Institute of Neuroscience, Brain Research Center, National Yang-Ming University, Taipei, Taiwan Department of Medicine, MacKay Medical College, New Taipei City, Taiwan Department of Anesthesiology, MacKay Memorial Hospital, Taipei, Taiwan MacKay Junior College of Medicine, Nursing, and Management, Taipei 112, Taiwan.
authors.forename: Chau-Fu
authors.initials: CF
authors.lastname: Cheng
authors.forename: Jen-Kun
authors.initials: JK
authors.lastname: Cheng
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Chen
authors.forename: Ruey-Horng
authors.initials: RH
authors.lastname: Rau
authors.forename: Yu-Cheng
authors.initials: YC
authors.lastname: Chang
authors.forename: Meei-Ling
authors.initials: ML
authors.lastname: Tsaur
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D000076122:Disks Large Homolog 4 Protein; D007839:Functional Laterality / Q000502:physiology*; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D006930:Hyperalgesia / Q000209:etiology / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D020932:Nerve Growth Factor / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009437:Neuralgia / Q000150:complications / Q000378:metabolism* / Q000473:pathology*; D016501:Neurites / Q000473:pathology; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051672:Shal Potassium Channels / Q000235:genetics / Q000378:metabolism; D013129:Spinal Puncture; D014162:Transfection; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D051672:Shal Potassium Channels; D020932:Nerve Growth Factor; D014446:Tyrosine 3-Monooxygenase