It is well known that acute and unbearable pain are alarm reactions for the body; therefore, pain is necessary for life to protect the body. However, chronic pain is only an aversive feeling that produces various physical symptoms, such as decreased appetite, lower satisfaction with life, anxiety, mood disturbance, depression and poor sleep. [1][2][3][4] These symptoms reduce the quality of life of patients. Of these symptoms induced by chronic pain, sleep disturbance is well known to influence the social life of patients. Patients with chronic pain, together with postherpetic neuralgia, diabetic peripheral neuropathy and complex regional pain syndromes, often experienced sleep disturbances, such as delayed sleep onset, and difficulty in maintaining sleep and remaining asleep [4][5][6][7][8][9][10][11] ; therefore, an animal model of these conditions is needed to develop useful medicine for insomnia.There have been a few papers about sleep patterns in chronic constriction injury (CCI) rats reported as a neuropathic pain model, 12,13) however, conflicting findings are demonstrated, that is, one paper showed no significant alterations of sleep parameters, whereas another reported the opposite results. It seems difficult to assess the effects of hypnotics for sleep disturbance using only CCI model rats.Therefore, in the present study, we investigated the changes of sleep patterns in rats with CCI under aversive conditions.
MATERIALS AND METHODS
AnimalsMale Sprague-Dawley rats weighing 235-265 g (Charles River Japan, Yokohama, Japan) were used. All animals were maintained in an air-conditioned room with controlled temperature (24Ϯ2°C) and humidity (55Ϯ15%). They were housed in aluminum cages with sawdust and kept under a light-dark cycle (lights on from 07:00 to 19:00). The animals were allowed free access to food and water, except during the experiments. All procedures involving animals were conducted in accordance with the Guidelines for Animal Experiments at Okayama University Advanced Science Research Center.Surgery The animals were anesthetized with pentobarbital sodium (Nembutal ® , 35 mg/kg, i.p., Abbott Laboratories, North Chicago, IL, U.S.A.), and then placed in stereotaxic apparatus (SR-5N, Narishige, Tokyo, Japan). For EEG recording, a stainless steel screw electrode (200 mm) was chronically implanted into the right frontal cortex (A: 0.5, L: 3.0) according to the atlas of Paxinos and Watson.14) To record the electromyogram (EMG), stainless steel wire electrodes (200 mm) were implanted into the dorsal neck muscle. The electrodes were connected to a miniature receptacle and the whole assembly was fixed to the skull with dental cement. At least 7 d were allowed for recovery from surgery.Surgery for Chronic Constriction Injury (CCI) Model Surgery was performed according to the method of Bennett and Xie.15) Rats were anesthetized with pentobarbital sodium (Nembutal ® , 35 mg/kg, i.p.). The left common sciatic nerve was exposed at the level of the mid-thigh. Proximal to the sciatic trifurcation, about 7 mm of ...