| Objective: Pain is a common clinical symptom. There is a pain-conduction system in nervous system as well as a complex pain-modulation network. Hippocampus is an important conformation of limbic system. Hippocampus formation is related with pain sensation and pain modulation besides learning, memory and emotion. Some researchs demonstrated that subcutaneous injection of formalin could change the discharge frequency of pain exciting neuron and pain inhibitory neuron in hippocampus,which indicated that hippocampus neuron took part in the sensation of nociceptive information .5-HT, c-fos and IL-2mRNA expression in hippocampus could be up-regulated by peripheral subcutaneous injection of formalin, which suggested peripheral nociceptive information could be transmitted to hippocampus, and its function and metabolism were changed.Recently, some non-classic transmitter play an important role in transmition of nociceptive information and pain-modulation. As a new transmitter, Carbon monoxide is also involved in many process of physiology and pathophysiology. HO is a rate-limiting enzyme by which CO is produced in our body. HO-1 is a subtype that could be induced by a variety of pathological conditions such as oxidative stress, and inflammatio and hypoxia.It was proved that the expression of NOS and the production of NO in hippocampus were increased during peripheral nociceptive information transmitted to hippocampus. In addition, research result shows that NOS/NO system have a closed relationship with HO/CO system, whether the HO-1 expression could be changed during formalin-induced inflammatory pain has not been reported .Thereby, our present study was undertaken to observe the changes of HO-1 expression including its time course in the rats hippocampus during formalin-induced inflammatory pain.Method: Thirth-six male SD rats (260-280g in weight) were divided randomly into 6 groups: Control group and formalin 6h,12h, 24h, 48h,72h groups. There were six rats in each group。Rats in Control group were directly sacrificed without other treatments. The weighted pain score of the injected paw within 1h after the formalin injection were measured ,then rats in other five groups were sacrificed at corresponding time following the formalin injection. The immunohistochemistry was used to observe the expression of HO-1 protein in hippocampal subregions.The number and grey degree of H0-1 neurons were measured by JEDA801D analysis system software. Moreover, thermal withdrawal latency and mechanical withdraw threshold of the injected area and the corresponding area in the paw contralateral to the injection were measured before the animals were sacrificed at the designed ending time points.Result: Injection with formalin into the ventral surface of the rat hind paw induced a biphasic spontaneous pain reaction, including flinches, scratching and biting the wounded paw. The flinches lasted 1 h or more. There were inflammatory responses such as red swell, strikingly at 24h and decreased step by step from then on.Compared to Control group, the thermal withdrawal latency and mechanical withdraw threshold were increased in the injected area after the formalin injection, while were decreased in the corresponding area in the paw contralateral to the injection, especially at 24h.Within the CA1 CA3 DG region of the hippocampus, the number and staining degree of HO-1 positive neurons began to increase 6h after the formalin injection . But the most obviously increase was at 24h (P<0.01).The number and staining degree of HO-1 positive neurons began to decrease 48h after the formalin injection but higher than Control group(P<0.05) ,and returned to normal level 72h after the formalin injection . There were no significant difference in the number, staining degree of HO-1 positive neurons between two sides of the hippocampus.Conclusion : Subcutaneous formalin injection produced a permanent hyperalgesia to heat and mechanical stimuli in the corresponding area in the paw contralateral to the injection, but an analgesia in the injected area. Peripheral nociceptive information induced by formalin inflammatory pain could induce the elevation of HO-1 expression in hippocampus subregions; The most obvious change was at 24h, and returned basically to normal level at 72h after the formalin injection .
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