The regulatory role of nitric oxide in morphine-induced analgesia in the descending path of pain from the dorsal hippocampus to the dorsolateral periaqueductal gray

Manizheh Karami | Mahboobeh Hashemi | Mohammadreza Zarrindast

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URL :   http://research.shahed.ac.ir/WSR/WebPages/Report/PaperView.aspx?PaperID=159423
Date :  2022/01/23
Publish in :    European Journal of Pain
DOI :  https://doi.org/DOI: 10.1002/ejp.1916
Link :  https://pubmed.ncbi.nlm.nih.gov/35090066/
Keywords :Nitric oxide, dorsal hippocampus, dorsolateral periaqueductal gray matter, morphine, analgesia

Abstract :

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Background: Nitric oxide (NO) levels in brain nuclei, such as the hippocampus and brainstem, are involved in morphine analgesia, but the relationship between the dorsal hippocampus (dH) and the dorsolateral periaqueductal gray matter (dlPAG) needs to be clarified, which is our goal. Methods: Wistar rats were simultaneously equipped with a stereotaxic device with unilateral guide cannula at dH and dlPAG. After recovery, they were divided into control and experimental groups. Formalin (50 μL of 2.5) was inoculated into the left hind paw of rat. Morphine (6 mg/kg) was administered intraperitoneally (i.p.) 10 min before formalin injection. L-Arginine (0.25, 0.5, 1 and 2 μg/rat), and L-NAME (0.25, 0.5, 1 and 2 μg/rat), unrelatedly or with the respect in the order of injection were used in the nuclei before morphine injection (i.p.). Activation of the neuronal NO synthase (nNOS) in the brains of all animals was measured using NADPH-diaphorase, a selective biochemical marker of nNOS. Results: Morphine reduced inflammatory pain in the early and late stages of the rat formalin test. The morphine response was attenuated by before injection of single L-arginine but not L-NAME in the two target areas. However, the acute phase result was stopped due to L-NAME pretreatment. When L-NAME was injected into dlPAG before injecting L-arginine at dH, the morphine response did not decrease at all, indicating a modulatory role of NO in dlPAG, which was confirmed by NADPH-d staining. Conclusions: High levels of NO in dlPAG may regulate pain process in downward synaptic interactions.