Rational: 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.
Objective: The present study evaluated effects of paeoniflorin on neuropathic pain and associated insomnia and the mechanisms involved.
Methods: 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.
Results: 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.
Conclusions: 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.
Keywords: C-Fos; Knockout mice; Sleep disturbance.