Abstract
Background: Neuropathic pain, largely resulting from primary lesions in the peripheral nerve or from malfunctions in the central nervous system, has an extremely negative impact on the quality of life of patients affected by this condition. The chronic constriction injury (CCI) model of peripheral nerve injury has provided a deeper understanding of nociception and the events contributing to the pathogenesis of chronic pain conditions. Loganin is isolated from Corni fructus, a well-known herb with glucose-lowering action and neuroprotective activity. This study aimed to investigate the molecular mechanisms of loganin in a rat model of CCI-induced neuropathic pain.
Methods: Sprague-Dawley rats were randomly divided into four groups: sham, sham+loganin, CCI and CCI+loganin. Loganin (5 mg/kg/day) was injected intraperitoneally starting at day 1 after surgery. Mechanical and thermal responses were assessed before surgery and at day 3, 7, 14 after CCI. Proximal and distal sciatic nerves (SNs) were isolated for western blots, confocal microscopy and enzyme-linked immunosorbent assay to analyze protein expression, immunoreactivity and proinflammatory cytokines.
Results: Behavior data show that thermal hyperalgesia and mechanical allodynia were reduced in loganin treated group as compared to CCI group. The neurobehavioral changes was correlated with the demyelination of Schwann cells, particularly in the distal stump of injured SN. Inflammatory proteins (TRAP-1, p-IκB, iNOS) and proinflammatory cytokines (TNF-α, IL-1β) induced by CCI were attenuated in the loganin treated group at day 7 after CCI. Loganin also blocked IκB phosphorylation (p-IκB). Double immunofluorescent staining further demonstrated that p-NFκB protein was reduced by loganin in peripheral glial cells at day 7 after CCI.
Conclusion: Based on these findings, we concluded that loganin has antiinflammatory and antihyperalgesia properties in CCI-induced neuropathic pain via decreases in TNF-α/NF-κB activation.
