Acute stress-induced antinociception is cGMP-dependent but heme oxygenase-independent

Endogenous carbon monoxide (CO), which is produced by the enzyme heme oxygenase (HO), participates as a neuromodulator in physiological processes such as thermoregulation and nociception by stimulating the formation of 3′,5′-cyclic guanosine monophosphate (cGMP). In particular, the acute physical restraint-induced fever of rats can be blocked by inhibiting the enzyme HO. A previous study reported that the HO-CO-cGMP pathway plays a key phasic antinociceptive role in modulating noninflammatory acute pain. Thus, this study evaluated the involvement of the HO-CO-cGMP pathway in antinociception induced by acute stress in male Wistar rats (250-300 g; n=8/group) using the analgesia index (AI) in the tail flick test. The results showed that antinociception induced by acute stress was not dependent on the HO-CO-cGMP pathway, as neither treatment with the HO inhibitor ZnDBPG nor heme-lysinate altered the AI. However, antinociception was dependent on cGMP activity because pretreatment with the guanylate cyclase inhibitor 1H-[1,2,4] oxadiazolo [4,3-a] quinoxaline-1-one (ODQ) blocked the increase in the AI induced by acute stress.

INTRACEPHALIC DIFFUSION AND SELECTIVE LABELING OF PROPIDIUM IODIDE INJECTED INTO THE LATERAL CEREBRAL VENTRICLE / 解剖学报

Injections of propidium iedide (PI) into the lateral cerebral ventricle (LV) ofthe rat resulted in a prominent abnormality characterized by tremor,ataxia,andnystagmus.The intensity of PI fluorescence in the parenchyma of the brain fadedgradually away from the injection site and ventricles to the surfaces of the brain. In the forebrain it was seen that PI fluorescence reached the most lateral part ofthe ipsilateral caudate putamen nucleus.A constant neuronal labeling was observedin the septohippocampal nuclei,the A8-9-10 dopaminergic cell groups of themidbrain,the dorsal raphe nucleus,the median raphe nucleus,neurons within anddorsal to the medial lemniscus of the caudal midbrain,and Furkinje cells of thecerebellum.This neuronal labeling was bilateral.No distinct labeling was seen inother areas of the brain.Combined with Faglu histofluorescence,it was found thatalmost all of the dopaminergic neurons in the midbrain exhibited PI fluorescence.No labeled non-dopaminergic neuron was seen in A8-9-10.With a transection ofthe unilateral medial forebrain bundle,a prominent accumulation of PI fluorescencewas seen within the distal segments of catecholaminergic fibers near the transection,but no accumulation of PI was seen in the proximal segments.With LV injectionof Evans blue(EB)or DAPI or ethidium bromide,animals did not exhibit anyvisible abnormality.In animals with LV injection of EB or DAPI,although somelabeled cells were seen in the distant areas of the brain,their distribution wasdistinctly different from that of PI labeling.The above results indicate that besidesconfirming the LV injection of PI results in a prominent abnormality and PI isselectively uptaken by Purkinje cells,we have found that:a)PI is able to enter theparenchyma from the cerebrospinal fluid and diffuse widely in the brain;b)LVinjection of PI results in a selective labeling in certain specific areas of the brain,and those selectively labeled cells in A8-9-10 all are dopaminergic neurons;c)these dopaminergi(?) cells are labeled through axonal uptake and retrograde transportof PI.