| Backgrounds and ObjectiveAnterior cingulate cortex （ACC） is an important brain structure and an importantpart of limbic system. Previous studies showed that ACC is responsible on advancedcognitive process，attention，emotional reaction，pain and so on. Schizophrenia is acommon psychotic with the highest global incidence,which is characterized byaffective disorder，thinking disorder and so on. Refractory schizophrenia is frequentlynoted clinically as hallucination,commit suicide and the treatment is hard. With thedevelopment of stereotaxic techniques and Psychosurgery, The ablativeprocedure,including ACC, Amygdaloid，anterior limb of internal capsule，dorsal medial nucleus of thalamus and nucleus accumbens，is used as an treatment forrefractory schizophrenia and has a good effect.However, the postoperative sidereactions as akinetic mutism or as apathy, pyrexia，temprary urinary incontinence areobserved.These phenomenon is related to lesion of ACC.Pain is a dynamic phenomenon and is made of emotional components and sensorycomponent. A good way to understand the physiology of pain is to follow thenociceptive signal pathways from the periphery to the brain. ACC is related toregulation of emotional components of pain. Recently, more and more evidencesupported the contributions of ACC in sensory component of pain. In ACC,nociceptive neurons activated by noxious electrical, mechanical or thermal stimuliwere identified. Behavioral studies indicated that electrical stimulation to cingulumbundle and surrounding cortical tissue （including ACC） increased hot plate andtail-flick latencies （Hardy,1985） and inhibited formalin-induced pain responses （Fuchset al.,1996）.Morphine-induced ACC activation could produce naloxone reversibleeffects in neuropathic pain model of spinal nerve ligation （LaGraize et al.,2006）.Although these results strongly support that ACC activation could produce inhibitoryeffect on pain processing,the neuronal substrate of ACC activation-mediated painmodulation remains uncertain at present.In spinal cord dorsal horn, wide-dynamic-range （WDR） neurons could responddifferentially over a broad range of stimulus intensities from very gentle to distinctlypainful levels of stimulation.These neurons received synaptic input from primaryafferent neurons and then mediated pain signals to other brain regions throughdifferent pain pathways （Price,2002）. Additionally, the activities of spinal neuronscould be modulated by a number of supraspinal sites such as midline periaqueductalgray-rostral ventromedial medulla （PAG-RVM） system, more lateral and caudal dorsalreticular nucleus and ventrolateral medulla, and forebrain areas including ACC,amygdala, dorsomedial nucleus of the hypothalamus and medial prefrontal cortex （Heinricher et al.,2009）.In a recent report, Senapati et al. evaluated the simultaneouschanges of WDR neurons in responses to mechanical stimulation during ACCstimulation and reported that ACC-mediated inhibitory effects could recover almostimmediately （1min） after termination of stimulation, namely short-term effect（Senapati et al.,2005）.Short-term inhibitory effect of ACC activity, however, was hardto explain the long-term （persisted for over30min） antinociceptive results observed inpain behavioral tests （Hardy,1985; Fuchs et al.,1996）. Present study is designed toexamine the potential long-term effects of ACC activation on spinal WDR neurons inresponses to different mechanical and electrical stimuli in adult rat.Methods:1．A clinical retrospective studies is proceeded in tangdu brain functional diseasescenter and the aim to evaluate the role of ACC in treatment of refractory schizophrenia.The patients is devided to2groups on criteria ACC and non-ACC of ablativeprocedure.Using psychoneurotic inventory,including SANS,ADL,HAMD,SAPS andetc,The positive symptom, negative symptoms and side effect will be analysed.2．Experimental animalsThe experiments were performed on male Sprague–Dawley albino rats （AnimalCenter of Fourth Military Medical University,Xi’an） weighing200–220g. the rat wasinitially anesthetized with pentobarbital, and then securely placed into a stereotaxicdevice with fixation of the head by bilateral ear bars. A tracheal cannula and a leftjugular vein catheter were inserted, and adequate anesthesia was confirmedintermittently during the whole experiment by examining whether the animal madespontaneous movements or had arousal responses to noxious pinch applied to the skinat time when the muscle relaxant wore off. A laminectomy was performed from T13toL1vertebrae to expose the spinal cord for recording the activity of WDR neurons.Electrical stimuli to bilateral ACC were delivered at100Hz,0.1ms duration, atintensity of20V for20s. To get the long-term effects of ACC activation, the responses of spinal WDR neurons were examined1min and5min after bilateral ACCstimulation.All results expressed as mean±SEM. The data was compared by one-way ANOVAand statistical differences were resolved post hoc using the Tukey post hoc test. P <0.05was to be statistical significance.Results:1．The ablative procedure is effective on controlling positive symptom inrefractory schizophrenia.It has no significant change on negative symptoms on per andpost-operation.The side effect,such as akinetic mutism or as apathy, pyrexia，tempraryurinary incontinence are observed is observed during a week on post-operation.2．The locations of bilateral stimulating electrodes in ACC were anteroposterior（AP）+1.7mm from Bregm, mediolateral （ML）±0.6mmand dorsoventral （DV）2.5mm. The location of recording electrode was in depth of0.4–1.4mm andmediolateral0.6–1.2mm in the lumbosacral enlargement of spinal cord.3．Twelve spinal WDR neurons were recorded in response to graded mechanicalstimulation （brush, pressure, and pinch） following bilateral ACC stimuli. Two out of12WDR neurons showed no changes in mechanical stimuli-induced responsesfollowing ACC stimulation （data not shown）.However, noxiousstimuli-evokedresponses of the other10WDR neurons were significant suppressed. Therepresentative responses of spinal WDR neurons to pressure and pinch stimuli weresuppressed after1and5min of bilateral ACC stimulation （intensity:20V; duration:0.1ms; frequency:100Hz）. In contrast,the same stimulation had no effect onbrush-induced response.Further statistic data demonstrated the different effects ofbilateral ACC stimulation on the response of spinal WDR neurons to three types ofmechanical stimuli.4．A train of16electrical stimuli （intensity:1.5times of threshold; pulse duration:2ms; frequency:0.5Hz） evoked typical wind-up responses in normal rat. The spinal WDR neuron spike discharges could remain for several seconds after the last electricalstimulation ceased, indicating the occurrence of after-discharge. Five minutes afterACC stimulation （intensity:20V; duration:0.1ms; frequency:100Hz）, the wind-upresponses were significantly decreased.. The total numbers of LR and AD weresignificantly decreased. However, ACC stimulation had no effects on total numbers ofER.Conclusions:1．According to the data,there is no sexual differences on the ablative procedure ofSCH.2．The two operation has no significant different on total treatment outcome inSCH.However,they have significant different on all kind of symptom.To positivesymptom,such as Mania， Delusion， Parapraxis， it appears significant effect,thereversion improvement rate is larger than50%.To Anxiety，Depression, ThoughtDisorder, the reversion improvement rate is smaller than50%.To Apathy, Disturbanceof attention, lack of interest，the ablative procedure is ineffective.3．The side effect is observed on post-operation. The incidence rate of akinetic mutism oras apathy, pyrexia，temprary urinary incontinence,is approximate60-80%and can recovery inone year.But the incidence rate of Anorexia，Juvenile behavior is approximate5-30%and ithas no change in one year.4．The non-ACC group has a lower incidence rate than ACC group,such as akineticmutism or as apathy, pyrexia，temprary urinary incontinence, Anorexia，Juvenile behavior.5．short-termACC activation could generate long-term inhibitory effects on theresponses of WDR neurons to noxious mechanical （pressure and pinch） and electricalstimuli.6．ACC activation could negatively regulate noxious information ascending fromspinal cord with long-term effect. |
PDF Full Text Request