Effective control of neuropathic pain by transient expression of hepatocyte growth factor in a mouse chronic constriction injury model

Autor: Junghun Lee, Sung Joong Lee, Kyeong Ryang Ko, Sunyoung Kim, Boram Nho, J.M. Lee
Rok vydání: 2018
Předmět:
Male
0301 basic medicine
microglia
Pharmacology
Biochemistry
Mice
Transcription Factor 3
plasmid DNA
0302 clinical medicine
Ganglia
Spinal
Mice
Inbred ICR
Microglia
biology
Hepatocyte Growth Factor
Gene Transfer Techniques
Constriction
Sciatic Nerve
gene therapy
medicine.anatomical_structure
Hyperalgesia
Neuropathic pain
Hepatocyte growth factor
Sciatic nerve
Cell activation
Neuroglia
Biotechnology
medicine.drug
Neurotrophin
Spinal Cord Dorsal Horn
Sensory Receptor Cells
Down-Regulation
03 medical and health sciences
Genetics
medicine
Animals
Humans
Muscle
Skeletal
Molecular Biology
Spinal Cord Injuries
business.industry
Macrophage Colony-Stimulating Factor
Research
Genetic Therapy
Spinal cord
Disease Models
Animal
030104 developmental biology
DRG
biology.protein
Neuralgia
VM202
Calcium Channels
business
030217 neurology & neurosurgery
Zdroj: The FASEB Journal
ISSN: 1530-6860
0892-6638
DOI: 10.1096/fj.201800476r
Popis: Hepatocyte growth factor (HGF) is a multifunctional protein that contains angiogenic and neurotrophic properties. In the current study, we investigated the analgesic effects of HGF by using a plasmid DNA that was designed to express 2 isoforms of human HGF—pCK-HGF-X7 (or VM202)—in a chronic constriction injury (CCI) –induced mouse neuropathic pain model. Intramuscular injection of pCK-HGF-X7 into proximal thigh muscle induced the expression of HGF in the muscle, sciatic nerve, and dorsal root ganglia (DRG). This gene transfer procedure significantly attenuated mechanical allodynia and thermal hyperalgesia after CCI. Injury-induced expression of activating transcription factor 3, calcium channel subunit α2δ1, and CSF1 in the ipsilateral DRG neurons was markedly down-regulated in the pCK-HGF-X7–treated group, which suggested that HGF might exert its analgesic effects by inhibiting pain-mediating genes in the sensory neurons. In addition, suppressed CSF1 expression in DRG neurons by pCK-HGF-X7 treatment was accompanied by a noticeable suppression of the nerve injury–induced glial cell activation in the spinal cord dorsal horn. Taken together, our data show that pCK-HGF-X7 attenuates nerve injury–induced neuropathic pain by inhibiting pain-related factors in DRG neurons and subsequent spinal cord glial activation, which suggests its therapeutic efficacy in the treatment of neuropathic pain.—Nho, B., Lee, J., Lee, J., Ko, K. R., Lee, S. J., Kim, S. Effective control of neuropathic pain by transient expression of hepatocyte growth factor in a mouse chronic constriction injury model.
Databáze: OpenAIRE
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