Antinociceptive And Hypnotic Activities Of Pregabalin In A Neuropathic Pain-like Model Of Mice

Objectives: Neuropathic pain is one of pain syndromes caused by sensory nervesystem injury or disease. In general, it is a chronic disease and can lead to differentlevels of sleep and/or mood disorder. Pregabalin, belongs to Gamma-aminobutyric aciddrugs, has been appeared in the market as the therapeutic drug for epilepsy in USA,UK, etc. In our study, we aimed to establish the neuropathic pain model in mice(Partial sciatic nerve ligation), investigated the function of pregabalin in curing theneuropathic pain, ameliorated of pain-related sleep disorders, and explored themechanism of pregabalin influencing sleep.Methods: A mouse model of chronic neuropathic pain induced by partial sciatic nerveligation (PSL) was employed, and the sleep disorder model in PSL mice wasestablished by combining the sleep-wakefulness recording and analysis system. Theeffects of pregabalin on thermal hyperalgesia and mechanical allodynia wereinvestigated in PSL mice. EEG and EMG were recorded to study the effect ofpregabalin to improve the sleep disorder in terms of amounts of sleep and wakefulness,number and duration of episodes, number of sleep-wake stage transitions, and EEGpower spectra in PSL mice from07:00to11:00; and the effect of pregabalin toinfluence the sleep-wakefuless structure during activity stage at night (21:00-01:00) inPSL model mice and normal mice. Immunohistochemistry experiment was used toobserve the effect of pregabalin to the numbers of c-Fos positive neurons in anteriorcingulate cortex (ACC).Results: PSL mice had the symptom of trigger pain hyperpathia, thermal hyperalgesiaand difficulty in falling sleep for over a month.①Intragastric administration ofpregabalin (25mg/kg) at09:00, after3h the pregabalin (25mg/kg) increased the mechanical threshold of PSL mice3.1times and prolong the thermal latency for59%.Pregabalin clearly exhibited analgesic effect without impairment of motor function.②Intragastric administration of pregabalin (25mg/kg) at06:30, increased the non-rapideye movement (NREM) sleep by40%during07:00-11:00, decreased the wakefulnesstime by38%, increased long-term NREM sleep and rapid eye movement (REM) sleep,decreased wakefulness times, decreased the transitions from NREM sleep towakefulness, and increased the transitions from NREM sleep to REM sleep.③Intragastric administration of pregabalin (25mg/kg) at20:30not influenced the sleepand wakefulness structure during activity stage at night (21:00-01:00) in both normalmice and PSL model mice.④Intragastric administration of pregabalin (25mg/kg) at06:30decreased the numbers of c-Fos positive neurons in anterior cingulate cortex(ACC).Conclusions: Pregabalin has analgesic effect to neuropathic pain model mice, and itcan also ameliorate the related sleep disorders at the same time. The effect of analgesiaand promoting sleep may have some correlation with suppressing the abnormallyexcited neurons in ACC.