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

Abstract

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.