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Gene transfer of a naked plasmid (pUDK‐HGF) encoding human hepatocyte growth factor attenuates skin/muscle incision and retraction‐induced chronic post‐surgical pain in rats
Author(s) -
Hu C.,
Lu Y.,
Chen X.,
Wu Z.,
Zhang Q.
Publication year - 2018
Publication title -
european journal of pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.305
H-Index - 109
eISSN - 1532-2149
pISSN - 1090-3801
DOI - 10.1002/ejp.1182
Subject(s) - hepatocyte growth factor , analgesic , medicine , western blot , stimulation , growth factor , pharmacology , anesthesia , chronic pain , chemistry , gene , receptor , biochemistry , psychiatry
Background Chronic post‐surgical pain (CPSP) remains a major clinical problem and is often refractory to current treatments. New analgesic medications and strategies for pain relief are needed. Hepatocyte growth factor (HGF) is known to be a multi‐functional growth factor and regulates various biological activities. Methods We investigated the analgesic effect and underlying mechanism of plasmid pUDK‐HGF encoding human HGF gene on CPSP induced by skin/muscle incision and retraction (SMIR) in rats. The possible changes of inflammatory factors, glial cell activation and pain sensitivity after pUDK‐HGF administration were investigated by ELISA, western blot and Von Frey tests, respectively. Results In behavioural assays, we found that a single intramuscular or intrathecal injection of pUDK‐HGF significantly attenuated mechanical hypersensitivity to von Frey stimulation of plantar ipsilateral hind paw after SMIR. Intramuscular injection of pUDK‐HGF promoted blood flow and proliferation of satellite cells and inhibited inflammatory cells recruitment, collagen accumulation and expression of pronociceptive factors. Intrathecal injection of pUDK‐HGF inhibited activation of spinal glial cells and production of inflammatory mediators induced by SMIR. Conclusions pUDK‐HGF has a strong analgesic potency and efficacy in CPSP induced by SMIR in rats. This study highlights a new strategy for the treatment of CPSP. Significance The CPSP occurs following various surgical procedures and remains a major clinical problem due to the lack of study on the mechanisms of CPSP. Our findings provide the first evidence that pUDK‐HGF attenuates SMIR‐induced pain behaviuors through peripheral or central mechanisms. The peripheral analgesic effect of pUDK‐HGF is associated with promoting tissue repair and inhibiting inflammatory response; furthermore, pUDK‐HGF inhibits activation of spinal glial cells and overexpression of inflammatory mediators in spinal cord. Therefore, naked pUDK‐HGF may be a potential therapeutic strategy for treatment of CPSP in clinic.