Anti-nociceptive effects of Sedum Lineare Thunb. on spared nerve injury-induced neuropathic pain by inhibiting TLR4/NF-κB signaling in the spinal cord in rats

• Published in: Biomedicine & pharmacotherapy Vol. 135; p. 111215
• Main Authors: Wang, Xin-ying, Ma, Hai-juan, Xue, Meng, Sun, Ya-lan, Ren, An, Li, Meng-qi, Huang, Zhi-hua, Huang, Cheng
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.03.2021; Elsevier
• Subjects: Analgesics - isolation & purification; Analgesics - pharmacology; Animals; Anti-Inflammatory Agents - isolation & purification; Anti-Inflammatory Agents - pharmacology; Cytokine; Cytokines - metabolism; Disease Models, Animal; HMGB1; Inflammation Mediators - metabolism; Male; Microglia - drug effects; Microglia - metabolism; Microglial activation; Neuralgia - metabolism; Neuralgia - physiopathology; Neuralgia - prevention & control; Neuropathic pain; NF-kappa B - metabolism; Pain Threshold - drug effects; Plant Extracts - isolation & purification; Plant Extracts - pharmacology; Rats; Rats, Sprague-Dawley; Sedum - chemistry; SedumLineare Thunb; Signal Transduction; Spinal Cord - drug effects; Spinal Cord - metabolism; Spinal Cord - physiopathology; TLR4/NF-κB signaling; Toll-Like Receptor 4 - metabolism; Cytokine; IKK; HMGB1; PWT; IL-1β; MyD88; IL-6; SNI; Neuropathic pain; IκB; p.o; NF-κB; SedumLineare Thunb; TNF-α; TRAF6; TLR4/NF-κB signaling; SLT; SEM; TLR4; Microglial activation
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2020.111215

[Display omitted] •SLT maybe acted as a promising therapeutic agent for neuropathic pain.•SLT treatment effectively inhibits SNI-induced the activation of spinal microglia.•SLT exhibits anti-inflammatory effect via re-balancing the cytokines in spinal cord.•SLT reverses SNI-provoked over-expression of spinal TLR4/NF-κB signaling pathway. Neuropathic pain is still a critical public health problem worldwide. Thereby, the search for novel and more effective strategies against neuropathic pain is urgently considered. It is known that neuroinflammation plays a crucial role in the pathogenesis of neuropathic pain. SedumLineare Thunb. (SLT), a kind of Chinese herb originated from the whole grass of Crassulaceae plant, was reported to possess anti-inflammatory activity. However, whether SLT has anti-nociceptive effect on neuropathic pain and its possible underlying mechanisms remains poorly elucidated. In this study, a rat model of neuropathic pain induced by spared nerve injury (SNI)was applied. SLT (p.o.) was administered to SNI rats once every day lasting for 14 days. Pain-related behaviors were assessed by using paw withdrawal threshold (PWT) and CatWalk gait parameters. Expression levels of inflammatory mediators and pain-related signaling molecules in the spinal cord were detected using western blotting assay. The results revealed that SLT (30, 100, and 300 mg/kg, p.o.) treatment for SNI rats ameliorated mechanical hypersensitivity in a dose-dependent manner. Application of SLT at the most effective dose of 100 mg/kg to SNI rats not only significantly blocked microglial activation, but also markedly reduced the protein levels of spinal HMGB1, TLR4, MyD88, TRAF6, IL-1β, IL-6, and TNF-α, along with an enhancement in gait parameters. Furthermore, SLT treatment dramatically inhibited the phosphorylation levels of both IKK and NF-κB p65 but obviously improved both IκB and IL-10 protein expression in the spinal cord of SNI rats. Altogether, these data suggested that SLT could suppress spinal TLR4/NF-κB signaling pathway in SNI rats, which might at least partly contribute to its anti-nociceptive action, indicating that SLT may serveas a potential therapeutic agent for neuropathic pain.