Go-sha-jinki-Gan (GJG) ameliorates allodynia in chronic constriction injury-model mice via suppression of TNF-α expression in the spinal cord.
BACKGROUND
Alternative medicine is noted for its clinical effect and minimal invasiveness in the treatment of neuropathic pain. Go-sha-jinki-Gan, a traditional Japanese herbal medicine, has been used for meralgia and numbness in elderly patients. However, the exact mechanism of GJG is unclear. This study aimed to investigate the molecular mechanism of the analgesic effect of GJG in a chronic constriction injury model.


RESULTS
GJG significantly reduced allodynia and hyperalgesia from the early phase (von Frey test, p<0.0001; cold-plate test, p<0.0001; hot-plate test p¼0.011; two-way repeated measures ANOVA). Immunohistochemistry and Western blot analysis revealed that GJG decreased the expression of Iba1 and tumor necrosis factor-a in the spinal cord. Double staining immunohistochemistry showed that most of the tumor necrosis factor-a was co-expressed in Iba1-positive cells at day 3 post-operation. GJG decreased the phosphorylation of p38 in the ipsilateral dorsal horn. Moreover, intrathecal injection of tumor necrosis factor-a opposed the anti-allodynic effect of GJG in the cold-plate test.


CONCLUSIONS
Our data suggest that GJG ameliorates allodynia in chronic constriction injury model mice via suppression of tumor necrosis factor-a expression derived from activated microglia. GJG is a promising drug for the treatment of neuropathic pain induced by neuro-inflammation.
Osaka University Graduate School of medicine.
Miho
M
Nakanishi
Osaka University Graduate School of medicineOsaka University Graduate School of medicineOsaka University Graduate School of medicineOsaka University Graduate School of medicine Osaka University Graduate School of Medicine Osaka University Graduate School of Medicine.
Aya
A
Nakae
Osaka University Graduate School of medicine.
Yuki
Y
Kishida
Osaka University Graduate School of medicine.
Kousuke
K
Baba
Osaka University Graduate School of medicine.
Noriko
N
Sakashita
Osaka University Graduate School of Medicine.
Masahiko
M
Shibata
Osaka University Graduate School of Medicine.
Hideki
H
Yoshikawa
Osaka University Graduate School of medicineOsaka University Graduate School of medicineOsaka University Graduate School of medicineOsaka University Graduate School of medicine Osaka University Graduate School of Medicine Osaka University Graduate School of Medicine hagihara.keisuke@gmail.com.
Keisuke
K
Hagihara
D000818:Animals; D001522:Behavior, Animal; D002851:Chromatography, High Pressure Liquid; D003080:Cold Temperature; D003250:Constriction; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000009:adverse effects / Q000627:therapeutic use*; D006930:Hyperalgesia / Q000188:drug therapy* / Q000378:metabolism*; D007278:Injections, Spinal; D008297:Male; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D004365:Drugs, Chinese Herbal; D014409:Tumor Necrosis Factor-alpha; C119642:gosha-jinki-gan