Go-sha-jinki-Gan (GJG) ameliorates allodynia in chronic constriction injury model mice via suppression of TNF-α expression in the spinal cord

Abstract

BackgroundAlternative 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.ResultsGJG significantly reduced allodynia and hyperalgesia from the early phase (von Frey test, p < 0.0001; cold-plate test, p < 0.0001; hot-plate test p = 0.011; two-way repeated measures ANOVA). Immunohistochemistry and Western blot analysis revealed that GJG decreased the expression of Iba1 and tumor necrosis factor-α in the spinal cord. Double staining immunohistochemistry showed that most of the tumor necrosis factor-α 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-α opposed the anti-allodynic effect of GJG in the cold-plate test.ConclusionsOur data suggest that GJG ameliorates allodynia in chronic constriction injury model mice via suppression of tumor necrosis factor-α expression derived from activated microglia. GJG is a promising drug for the treatment of neuropathic pain induced by neuro-inflammation.

An herbal medicine, Go-sha-jinki-gan (GJG), increases muscle weight in severe muscle dystrophy model mice

“…MF feed containing 4% GJG was produced by Oriental Yeast Co., Ltd. MF without GJG was also purchased from Oriental Yeast Co. and used for a control. In the previous study, the dose dependent maximum effect of GJG was 4% GJG, among the tested dosages of 0.5e4% [20]. Hence, in the present study, we treated DBA/2-mdx mice with 4% GJG food.…”

miR‐15b mediates oxaliplatin‐induced chronic neuropathic pain through BACE1 down‐regulation

“…In the present study, although we did not examine whether miR‐15b up‐regulation and subsequent BACE1 inhibition induced cold allodynia, the involvement of several molecules whose functions are regulated by BACE1 has been previously examined in this noxious cold sensation. For example, intrathecal injection of TNFα, whose receptor is regulated by BACE1, affects the response in the cold‐plate test (Nakanishi et al, ).…”

Searching for analgesic drug candidates alleviating oxaliplatin‐induced cold hypersensitivity in mice

“…Of note, among methods for measuring thermally evoked pain in animals, only “cold methods” are generally advised as oxaliplatin induces cold hypersensitivity but not heat hypersensitivity (Xiao, Zheng, & Bennett, ). For this purpose, researchers use different tests: acetone drop test (Ito, Kobuchi, Shimizu, & Katsuyama, ), cold water test (K. Sałat et al., ), and cold plate test (Sałat, Furgała, & Sałat, ); various temperatures the oxaliplatin‐treated animal is exposed to—ranging from −4°C (Hache et al., ) through 0°C (Pevida, Lastra, Hidalgo, Baamonde, & Menéndez, ), 2°C (Mika, Osikowicz, Makuch, & Przewlocka, ; Nakanishi et al., ), 4°C (Berrocoso et al., ; Hache et al., ; Masocha & Parvathy, ) to 5°C (Sambasevam et al., ; Zhao et al., ); different time points at which they assess animals’ nociceptive threshold—from 2 hr (Zhao et al., ) to 7 days after oxaliplatin injection (Hache et al., ; Zhao et al., ); and distinct behavioral measures taken as end‐points: paw withdrawal latencies (i.e., latencies to paw licking and paw shaking) (Pevida et al., ), only jumping behavior (Hache et al., ), or lifting behavior (Mika et al., ), escape behaviors graded with a score from no response to vigorous activity (i.e., jumping) (Zhao et al., ) or the duration of the nocifensive response (Nakanishi et al., ). In these experimental conditions, both rat (Ito et al., ) and mouse strains are used (reviewed in Marmiroli et al., ; Sałat et al., ).…”