Evaluation Of Brain Induced Pain By Open Field Test

Recently，the value of pain in medicine has been a broad consensus. It is thefifth vital sign besides the body temperature, blood pressure, pulse and respiration.Pain has two sides. It is physiologically significant as a survival alert system, andtherefore can be called physiological pain (or "good pain"). In addition, in thepathological state, it negatively affects living according to the damage of thebrain function and the entire body function. Drug and non-drug treatments are notideal to this kind of pain, so it is called pathological pain or chronic intractablepain, which is accompanied by spontaneous pain, hyperalgesia, paresthesia, orsensory loss.During the past fifty years, behavior evaluation methods are indispensable inthe experimental research of pain test. They are essential in the evaluation ofanalgesic efficacy and safety of drugs. Usually, pain behavior involves threelevels of compositions induced by spinal cord and brain as follows.1. Painbehavior mediated by spinal segments.2. Pain behavior mediated by supraspinalstructure.3. Pain behavior mediated by cerebral cortex. However, in theconventional experiments, people know much about1and2, but little about3.Especially, the pain behavior induced by brain is very important in the evaluation of characters of pathological pain and its co-morbidities, such as anxiety, fear,disappointment and depression. Therefore, this journal will use the explorationand open field to evaluate the tissue injured pain and the nerve injured pain,expecting to establish the qualitative and quantitative methods of evaluation ofthe cerebral cortex mediated pain behavior, which will help the research on theanalgesia and treatment of the new pain-related diseases.Methods:1. Chose of the models: we selected the most commonly usedformalin test and bee venom (BV) test as the animal models to evaluate the tissueinjured pain. And we selected the spared nerve injury models to evaluate thenerve injured pain.2. Exploration and open field test: we used thecomputer-assisted video-tracing hole-exploring open field test in our lab. Thisequipment is designed according to the habits of rodents and composed of fourindependent dark anti-noise boxes （70×70×70cm） for observation and acamera. The video is controlled by a computer and the open field video analysissystem3.0, which can get the parameters (the total distance, the central distance,the sides distance, the corners distance, the hole exploration) automatically.3.Statistical analysis methods: Mann-Whitney U–test.Results:1. In the open field, rats aged3-4weeks had poor ability to adaptthe environment and needed30-40minutes to adapt. While rats aged7-8weekshad a better ability and they could stop moving after20minutes, so rats at thisage are fit for the behavior research in the open field. Injection of formalin or BVto the center of the plantars could induce the spontaneous pain of rats.3-5minutes after injection of formalin, it appeared spontaneous flinches, whichlasted for10-15minutes. Then it appeared the second phase of fliches,accompanied by licking. After injection of BV to the center of flantar, the injectedarea became red and swollen and this appearance expanded to other areas. The spontaneous flinches lasted for1-2hours. Besides that, rats had mechanical andheat hyperalgesia, which lasted for72-96hours and were consistent with theredness and swollen.3.8of12rats in the saline group could adapt to theenvironment in the second10minutes.2rats of it were active and could adapt tothe environment in the third10minutes. The other2rats stayed in the corners inthe4th ten minutes or kept it but began to move in the fifth ten minutes. However,in the formalin group,9rats were active and could’t stop moving until the4th tenminutes, the other3could stop the exploration in the second ten minutes. In theBV group, most rats could stop movement from first to the second ten minutes,and only5rats continued to move from the20th to30th minutes,1rat couldn’tstop moving until the fifth ten minutes. Rats of the formalin group and BV groupspent more time in the center and sides in variance. The formalin group exploredmore holes than the saline group.4. One week after the selected injury of sciaticnerve, the rats’ pathological pain reached the peak and lasted for about1month.The rat’ s paw of injured side everted and mopped on the floor when walking.3rats of the sham group and SNI group were still moving during the fifith tenminutes. Another3of the sham group stopped moving gradually in the third tenminutes, but only1of the SNI group could’t stop moving until the40th-50thminutes,2of it couldn’t stop moving until the20th-30th minutes. The SNI groupmoved less than the na ve group and the sham group in the first time course, butthey adapted to the environment more slowly though without any variance. Therewas also not any variance in the time spent at any area and hole explorations.Conclusion:1. Compared with the immature rats, adult rats were morequickly to adapt in the open field. In addition, they acted more stably and weresuitable to do the behavior evaluation. While the immature rats are not suitable tobe used in the research on the behavior induced by brain.2. Compared with the saline group, both the inflammatory persistent pain models (BV group andformalin group) had the spontaneous pain behaviors such as flinches and licks,but they performed differently in the open field-the former group had less activemovements and explored a decrease number of holes because of hyperalgesia,while the latter group had more active movements and explored an increasenumber of holes because of hypoalgesia or analgesia. What’s more, comparedwith the saline group, the formalin group explored more in the central area, whilethe BV group explored less in the central area but more in the corners, indicatingthat though both of them have spontaneous pain, but whether they have thehyperalgesia will affect their behavior more largely. Animals with hyperalgesiawill perform recession and the loss of curiosity, while animals only appearespontaneous pain will be more likely perform mood of anxiety.3. Both the sciaticnerve-injured rats and BV-injected rats had notable mechanical hyperalgesia andcouldn’t or rarely touched the ground. The had less active movements in variance,performed less in the central area and explored less holes, indicating that thehyperalgesia affects the rats’ active movement and curiosity seriously and leadsthe abnormal change of their brain function.