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

Impairment of peripheral nerve regeneration by insufficient activation of the HGF/c-Met/c-Jun pathway in aged mice

“…As shown in Figure 4 A, the frequency of withdrawal behavior in the nerve-injured young animals was significantly ameliorated in pCK-HGF-X7 i.m. injected mice, consistent with the analgesic effects reported in the previous studies [ 8 , 10 ]. When the HGF-expressing plasmid DNA was injected into 1-year-old aged animals, the level of frequency was comparable between the group administered with pCK (control vector) and pCK-HGF-X7, indicating that the HGF protein expressed from pCK-HGF-X7 had a minimal analgesic effect in aged condition ( Figure 4 B).…”

“…To further investigate whether the c-Met signaling pathway was functionally impaired in the aged mice, we tested the efficacy of HGF-expressing plasmid DNA (pCK-HGF-X7) as this plasmid DNA has been reported to show analgesic effects in a murine peripheral neuropathic pain model through c-Met receptor [ 8 , 10 ]. We induced sciatic nerve injury by crushing the sciatic nerve in both young and aged animals.…”

Pathology of pain and its implications for therapeutic interventions

“…Topical administration of the naked HGF plasmids suppresses macrophage infiltration in DRG, concomitantly diminishing the release of proinflammatory factors, including IL-1β, IL-6, and TNF-α. 707 , 708 This pain relief strategy has passed phase III study on diabetic peripheral neuropathy, 709 which is the gene therapy closet to clinical application to date. Similarly, IL-10 delivered by naked plasmids induces lasting neuropathic pain suppression independently of its endogenous form.…”