A Morphological Study Of Heme Oxygenase-1 Induced By Pain In Rat Nervous System

Although it has been discovered that some nontraditional transmitter ( such as NO) played an important role in the modulation of algaesthesis, the effect of carbon monoxide (CO), a newly found transmitter, in algaesthesis has not yet been fully demonstrated. Heme oxygenase (HO) is the rate-limiting enzyme of the CO production, and HO-1 is the induced form of HO. Under normal conditions, HO-1 can not be found in the nervous system physiologically except for some special areas. According to the recent studies, the trauma of peripheral organs can induce the expression of HO-1 in the brain tissue, which indicated that there might be some relationship between HO-1/CO and the modulation of injury stimulus. But the morphological study about which part in the nervous system getting involved is still unclear.Objective: To observe the changes and distribution of HO-1 expression in rat nervous system following inflam- matory pain, and elucidate which part in the nervous system relates to the modulation of pain.Methods: The model of inflammatory pain of rats was made by the subcutaneous injection of formalin solution. The tissue distribution of the HO-1 expression induced by pain in the nervous system was investigated by immunohistochemi- stry. Eighteen healthy SD rats were divided into two groups randomly: the control group and the pain group (n=9 in both groups), then the model was made by injecting formalin solution (0.2 ml, 5% ) to the right hind paw of rats. After 12 hours, rats were anesthetized, then perfused and fixed through the ascending aorta of heart with 250 ml, 4 % citromint ( prepared by 0.1M PBS, pH=7.4) . After that, the dorsal root ganglion of lumboscsaral segment, spinal cord of lumboscsaral segment, brain stem, diencephalons and telencephalon were taken out respectively. Coronal sections of the different samples were cut and stained by anti-HO-1 antibody of rats using immunohistochemistry, then observed under light microscope and photographed. Results: 1. HO-1 positive signals could be found scattering in the gray matter of spinal cord, red nucleus, nucleus of oculomotor nerve and thalamic reticular nucleus in the normal rats. 2. HO-1 expression could be induced by inflammatory pain stimulus in doral root ganglion, gray matter of spinal cord, reticular formation of brain stem, periaqueductal gray, substantia nigra, hypothalamic paraventricular nucleus and supraoptic nucleus, caudate- putamen, septal nucleus, area of frontal and parietal cortex and neuroglial cells of white matter of lumboscaral segment.Conclusions: Peripheral inflammatory pain can induce the expression of HO-1 in dorsal root ganglion, gray matter of spinal cord, reticular formation of medulla oblongata, periaqueductal gray, area of frontal cortex etc which have close relationship to the modulation of pain, together with some stress-related areas, such as paraventricular nucleus and supraoptic nucleus. From above It could be concluded that HO-1/CO play a role in the modulation effects on pain sense and pain reaction .