salvianolic-acid-B and Neuralgia

Spinal cord injury (SCI) is a common type of injury, and about half of patients affected by SCI will suffer from neuropathic pain within a year after injury. However, the treatment effect of neuropathic pain is far from satisfactory. Our study attempted to reveal whether salvianolic acid B (SalB) could relieve the neuropathic pain caused by SCI in mice by inhibiting the Toll-like receptor 4 (TLR4)/Myeloid differentiation factor 88 (MyD88) pathway.. The mice were randomly divided into a sham group, model group, high-dose treatment group, and low-dose treatment group. The high- and low-dose groups received varying doses of SalB after modeling.. The increase of pain sensitivity was evaluated by detecting paw withdrawal mechanical threshold and withdrawal thermal latency. Messenger RNA and protein expression levels of TLR4 and myD88 were detected by using quantitative reverse-transcription polymerase chain reaction and western blot, respectively. Compared with the model group, there was a significant reduction in paw withdrawal mechanical threshold and withdrawal thermal latency after SalB treatment.. SalB reduced the release of tumor necrosis factor-α and substance P by inhibiting the TLR4/MyD88 pathway in the SCI mouse model. This not only resulted in lower pain, but also contributed to long-term relief of mechanical hyperalgesia.

Topics: Animals; Benzofurans; Hyperalgesia; Male; Mice; Myeloid Differentiation Factor 88; Neuralgia; Pain Threshold; Random Allocation; Spinal Cord Injuries; Toll-Like Receptor 4

Salvianolic acid B (SalB) represents the most characteristic constituent of Salvia miltiorrhiza Bge. with a strong free radicals scavenger activity. This property may be useful in the treatment of some severe chronic diseases, where there is an imbalance of reactive oxygen species formation and where intracellular reactive oxygen and nitrogen species level can cause severe cell damage and even cell death. In particular, SalB can protect against the oxidative stress as well as the antioxidant superoxide dismutase and reduced activity of glutathione, important determinants of neuropathological and behavioural consequences in neuropathic pain. This is a chronic disease defined by the WHO as an untreatable illness because therapeutics are unsatisfactory in many cases and there is an urgent need to discover and develop novel active drugs. In the present work, SalB has been extracted and purified with an efficient and rapid method from the roots and rhizome of S. miltiorrhiza Bge. It was firstly submitted to pharmacological studies using the paw-pressure test, in an animal model of neuropathic pain where a peripheral mono neuropathy was produced by a chronic constriction injury of the sciatic nerve. SalB was effective against mechanical hyperalgesia when administered intraperitoneally at the dose of 100mg/kg, 15 min after administration. Due to the poor chemical stability and bioavailability of SalB, liposomes were developed as drug carriers for parental administration. SalB-loaded liposomes were characterised in terms of particle size, polydispersity index, encapsulation efficacy and morphology. According to the in vivo studies, encapsulation, especially into PEGylated liposomes, increased and prolonged the antihyperalgesic activity 30 min after i.p. administration and the effect was still significant at 45 min. Thus, PEGylated formulation ameliorated the performance of drug delaying, increasing and prolonging in time its antihyperalgesic effect.

Topics: Analgesics; Animals; Benzofurans; Hyperalgesia; Ligation; Male; Microscopy, Electron, Transmission; Neuralgia; Pain Measurement; Pain Threshold; Particle Size; Rats; Rats, Sprague-Dawley; Sciatic Nerve; Sciatica; Static Electricity; Surface Properties; Unilamellar Liposomes