Nerve growth factor–induced synapse-like structures in contralateral sensory ganglia contribute to chronic mirror-image pain. Issue 11 (November 2015)

• Record Type: Journal Article
• Authors: Cheng, Chau-Fu; Cheng, Jen-Kun; Chen, Chih-Yang; Rau, Ruey-Horng; Chang, Yu-Cheng; Tsaur, Meei-Ling
• Is Part Of: Pain. Volume 156:Issue 11(2015)
• Publication Date: 2015-11
• Subjects: Contralateral pain -- Spinal nerve ligation -- Mechanical hypersensitivity -- Dorsal root ganglion -- Nociceptor excitability -- Neurite sprouting; Pain -- Periodicals; Douleur -- Périodiques; Anesthésie -- Périodiques; Pain; Electronic journals; Periodicals; Electronic journals; 616.0472
• DOI: 10.1097/j.pain.0000000000000280
• Languages: English
• ISSNs: 0304-3959

Abstract

Abstract : 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. Abstract : Supplemental Digital Content is Available in the Text.Elevated nerve growth factor after peripheral nerve injury induces neurite sprouting and the formation of synapse-like structures within the contralateral dorsal root ganglion, leading to the development of chronic mirror-image pain.