Intramuscular injection of a plasmid DNA vector expressing hepatocyte growth factor (HGF) ameliorated pain symptoms by controlling the expression of pro-inflammatory cytokines in the dorsal root ganglion.

Boram Nho, Kyeong Ryang Ko, Sunyoung Kim, Junghun Lee

Biochemical and biophysical research communications 2022 Jun 04

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Hepatocyte growth factor (HGF) is a secretory protein that is involved in various biological activities such as angiogenesis, neuroprotection, and anti-inflammatory effects. Intramuscular injection of an HGF-encoding plasmid DNA (pCK-HGF-X7) has been shown to produce pain-relieving effects in a rodent model and patients with neuropathic pain.To further investigate the underlying mechanism, we investigated the anti-inflammatory effects of HGF in the context of neuropathic pain. Consistent with previous data, intramuscular injection of pCK-HGF-X7 showed pain relieving effects up to 8 weeks and pharmacological blockade of the c-Met receptor hindered this effect, which suggest that the analgesic effect was c-Met receptor-dependent. At the histological level, macrophage infiltration in the dorsal root ganglion (DRG) was significantly decreased in the pCK-HGF-X7 injected group. Moreover, HGF treatment significantly downregulated the LPS-mediated induction of pro-inflammatory cytokines in primary cultured DRG neurons. Taken together, these data suggest that HGF-encoding plasmid DNA attenuates neuropathic pain via controlling the expression of pro-inflammatory cytokines. Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Boram Nho, Kyeong Ryang Ko, Sunyoung Kim, Junghun Lee. Intramuscular injection of a plasmid DNA vector expressing hepatocyte growth factor (HGF) ameliorated pain symptoms by controlling the expression of pro-inflammatory cytokines in the dorsal root ganglion. Biochemical and biophysical research communications. 2022 Jun 04;607:60-66