peoniflorin and Sleep-Initiation-and-Maintenance-Disorders

Neuropathic pain is frequently comorbid with sleep disturbances. Paeoniflorin, a main active compound of total glucosides of paeony, has been well documented to exhibit neuroprotective bioactivity.. The present study evaluated effects of paeoniflorin on neuropathic pain and associated insomnia and the mechanisms involved.. The analgesic and hypnotic effects of paeoniflorin were measured by mechanical threshold and thermal latency, electroencephalogram (EEG) and electromyogram, and c-Fos expression in a neuropathic pain insomnia model.. The data revealed that paeoniflorin (50 or 100 mg/kg, i.p.) significantly increased the mechanical threshold and prolonged the thermal latency in partial sciatic nerve ligation (PSNL) mice. Meanwhile, paeoniflorin increased non-rapid eye movement (NREM) sleep amount and concomitantly decreased wakefulness time. However, pretreatment with l,3-dimethy-8-cyclopenthylxanthine, an adenosine A1 receptor (R, A1R) antagonist, abolished the analgesic and hypnotic effects of paeoniflorin. Moreover, paeoniflorin at 100 mg/kg failed to change mechanical threshold and thermal latency and NREM sleep in A1R knockout PSNL mice. Immunohistochemical study showed that paeoniflorin inhibited c-Fos overexpression induced by PSNL in the anterior cingulate cortex and ventrolateral periaqueductal gray.. The present findings indicated that paeoniflorin exerted analgesic and hypnotic effects via adenosine A1Rs and might be of potential use in the treatment of neuropathic pain and associated insomnia.

Topics: Adenosine A1 Receptor Antagonists; Analgesics; Animals; Electroencephalography; Electromyography; Glucosides; Hypnotics and Sedatives; Mice; Mice, Knockout; Monoterpenes; Neuralgia; Neuroprotective Agents; Pain Threshold; Proto-Oncogene Proteins c-fos; Psychomotor Performance; Receptor, Adenosine A1; Sciatic Nerve; Sleep; Sleep Initiation and Maintenance Disorders

To investigate the sedative and hypnotic activity of paeoniflorin and freeze-dried Sini San powder on mice and provide a reliable method for determining the pharmacodynamic material basis of Sini San.. Male adult mice weighing 20-22 g were used in this study. Three experiments were carried out. Synergism with pentobarbital was used as an index for hypnotic effect. Loss of the righting reflex was used to determine the start of sleep. Sleep latency and sleeping time were recorded in each experiment.. The coefficient of variation of the suprathreshold dose (55 mg/kg) was significantly lower than that of the threshold dose. The sleep latency of mice was significantly decreased, and the sleeping time of mice was significantly prolonged. The effects of paeoniflorin and Sini San on prolonging the sleeping time of mice induced by pentobarbital sodium were significantly stronger than those in the control group.. Paeoniflorin produces significant sedative and hypnotic effects, and there is an obvious dose-effect relationship.

Topics: Animals; Benzoates; Bridged-Ring Compounds; Drugs, Chinese Herbal; Glucosides; Humans; Hypnotics and Sedatives; Male; Mice; Monoterpenes; Pentobarbital; Sleep; Sleep Initiation and Maintenance Disorders