Loganin prevents chronic constriction injury-provoked neuropathic pain by reducing TNF-α/IL-1β-mediated NF-κB activation and Schwann cell demyelination

• Published in: Phytomedicine (Stuttgart) 2020-02, Vol.67, p.153166-153166, Article 153166
• Main Authors: Chu, Li-Wen, Cheng, Kuang-I, Chen, Jun-Yih, Cheng, Yu-Chi, Chang, Yu-Chin, Yeh, Jwu-Lai, Hsu, Jong-Hau, Dai, Zen-Kong, Wu, Bin-Nan
• Format: Article
• Language: English
• Subjects: Analgesics, Non-Narcotic - pharmacology; Animals; Chronic constriction injury; Chronic Pain - drug therapy; Chronic Pain - metabolism; Chronic Pain - pathology; Constriction; Cytokines - metabolism; Hyperalgesia - drug therapy; Hyperalgesia - metabolism; Hyperalgesia - pathology; Interleukin-1beta - metabolism; Iridoids - pharmacology; Loganin; Male; Neuralgia - drug therapy; Neuralgia - metabolism; Neuralgia - pathology; Neuropathic pain; NF-kappa B - metabolism; NF-κB; Proinflammatory cytokines; Rats, Sprague-Dawley; Schwann cells; Schwann Cells - drug effects; Schwann Cells - metabolism; Schwann Cells - pathology; Sciatic Nerve - drug effects; Sciatic Nerve - metabolism; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0944-7113; 1618-095X
• DOI: 10.1016/j.phymed.2019.153166

Peripheral nerve injury can produce chronic and ultimately neuropathic pain. The chronic constriction injury (CCI) model has provided a deeper understanding of nociception and chronic pain. Loganin is a well-known herbal medicine with glucose-lowering action and neuroprotective activity. This study investigated the molecular mechanisms by which loganin reduced CCI-induced neuropathic pain. Sprague–Dawley rats were randomly divided into four groups: sham, sham+loganin, CCI and CCI+loganin. Loganin (1 or 5 mg/kg/day) was injected intraperitoneally once daily for 14 days, starting the day after CCI. For behavioral testing, mechanical and thermal responses were assessed before surgery and on d1, d3, d7 and d14 after surgery. Sciatic nerves (SNs) were collected to measure proinflammatory cytokines. Proximal and distal SNs were collected separately for Western blotting and immunofluorescence studies. Thermal hyperalgesia and mechanical allodynia were reduced in the loganin-treated group as compared to the CCI group. Loganin (5 mg/kg/day) prevented CCI from inducing proinflammatory cytokines (TNF-α, IL-1β), inflammatory proteins (TNF-α, IL-1β, pNFκB, pIκB/IκB, iNOS) and receptor (TNFR1, IL-1R), adaptor protein (TRAF2) of TNF-α, and Schwann cell demyelination and axonal damage. Loganin also blocked IκB phosphorylation (p-IκB). Double immunofluorescent staining further demonstrated that pNFκB/pIκB protein was reduced by loganin in Schwann cells on d7 after CCI. In the distal stumps of injured SN, Schwann cell demyelination was correlated with pain behaviors in CCI rats. Our findings indicate that loganin improves CCI-induced neuroinflammation and pain behavior by downregulating TNF-α/IL-1β-dependent NF-κB activation. [Display omitted]