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Papers of the Week

Papers: 21 May 2022 - 27 May 2022


Animal Studies

2022 May 25


The contributions of mu-opioid receptors on glutamatergic and GABAergic neurons to analgesia induced by various stress intensities.


Du Y, Yu K, Yan C, Wei C, Zheng Q, Qiao Y, Liu Y, Han J, Ren W, Liu Z
eNeuro. 2022 May 25.
PMID: 35613854.


The endogenous opioid system plays a crucial role in stress-induced analgesia. Mu-opioid receptors (MORs), one of major opioid receptors, are expressed widely in sub-populations of cells throughout the central nervous system. However, the potential roles of MORs expressed in glutamatergic (MOR) and γ-aminobutyric acidergic (MOR) neurons in stress-induced analgesia remains unclear. By examining tail-flick latencies to noxious radiant heat of male mice, here we investigated the contributions of MOR and MOR to behavioral analgesia and activities of neurons projecting from periaqueductal gray (PAG) to rostral ventromedial medulla (RVM) induced by a range of time courses of forced swim exposure. The moderate but not transitory or prolonged swim exposure induced a MOR-dependent analgesia, although all of these three stresses enhanced β-endorphin (β-EP) release. Selective deletion of MOR but not MOR clearly attenuated analgesia and blocked the enhancement of activities of PAG-RVM neurons induced by moderate swim exposure. Under transitory swim exposure, in contrast, selective deletion of MOR elicited an analgesia behavior via strengthening the activities of PAG-RVM neurons. These results indicate that MOR-dependent endogenous opioid signaling participates in nociceptive modulation in a wide-range, not limited to moderate, of stress intensities. Endogenous activation of MOR exerts analgesia whereas MOR produces anti-analgesia. More importantly, with increasement of stress intensities, the efficiencies of MORs on nociception shifts from balance between MOR and MOR to biasing towards MOR mediated processes. Thus, our results point to cellular dynamic characters of MORs expressed in excitatory and inhibitory neurons in pain modulation under various stress intensities.Mu-opioid receptors (MORs) are one of major opioid receptors playing a critical role in stress-induced analgesia, they are widely expressed on different types of neurons, but the potential roles of them expressed in glutamatergic (MOR) and γ-aminobutyric acidergic (MOR) neurons are poorly understood. This work clarifies the divergent roles of MOR and MOR in analgesia under various swim stress intensities. We demonstrate that MOR are essential for stress-induced analgesia, whereas MOR elicit an anti-analgesic like response. The contributions of MOR and MOR to analgesia depends on stress intensity, their opposite effects neutralizing each other under transitory stress and then biasing towards MOR under moderate stress. This report appraises different roles for these neuronal populations' MORs in modulating opioid-dependent stress-induced analgesia.