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Papers of the Week

Papers: 22 Jun 2019 - 28 Jun 2019

Animal Studies

2019 Jun 25

Cell Rep



Editor's Pick

Microglia Are Indispensable for Synaptic Plasticity in the Spinal Dorsal Horn and Chronic Pain.


Zhou L-J, Peng J, Xu Y-N, Zeng W-J, Zhang J, Wei X, Mai C-L, Lin Z-J, Liu Y, Murugan M, Eyo UB, Umpierre AD, Xin W-J, Chen T, Li M, Wang H, Richardson JR, Tan Z, Liu X-G, Wu L-J
Cell Rep. 2019 Jun 25; 27(13):3844-3859.e6.
PMID: 31242418.


Spinal long-term potentiation (LTP) at C-fiber synapses is hypothesized to underlie chronic pain. However, a causal link between spinal LTP and chronic pain is still lacking. Here, we report that high-frequency stimulation (HFS; 100 Hz, 10 V) of the mouse sciatic nerve reliably induces spinal LTP without causing nerve injury. LTP-inducible stimulation triggers chronic pain lasting for more than 35 days and increases the number of calcitonin gene-related peptide (CGRP) terminals in the spinal dorsal horn. The behavioral and morphological changes can be prevented by blocking NMDA receptors, ablating spinal microglia, or conditionally deleting microglial brain-derived neurotrophic factor (BDNF). HFS-induced spinal LTP, microglial activation, and upregulation of BDNF are inhibited by antibodies against colony-stimulating factor 1 (CSF-1). Together, our results show that microglial CSF1 and BDNF signaling are indispensable for spinal LTP and chronic pain. The microglia-dependent transition of synaptic potentiation to structural alterations in pain pathways may underlie pain chronicity.