Nerve growth factor-induced synapse-like structures in contralateral sensory ganglia contribute to chronic mirror-image pain

作者：Cheng Chau Fu; Cheng Jen Kun; Chen Chih Yang; Rau Ruey Horng; Chang Yu Cheng; Tsaur Meei Ling^*

来源：Pain, 2015, 156(11): 2295-2309.

DOI：10.1097/j.pain.0000000000000280

• Contra lateral pain
• Spinal nerve ligation
• Mechanical hypersensitivity
• Dorsal root ganglion
• Nociceptor excitability
• Neurite sprouting

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.

• 出版日期2015-11