RT Journal Article
SR Electronic
T1 The Contributions of Mu-Opioid Receptors on Glutamatergic and GABAergic Neurons to Analgesia Induced by Various Stress Intensities
JF eneuro
JO eNeuro
FD Society for Neuroscience
SP ENEURO.0487-21.2022
DO 10.1523/ENEURO.0487-21.2022
VO 9
IS 3
A1 Du, Yinan
A1 Yu, Kexin
A1 Yan, Chuanting
A1 Wei, Chunling
A1 Zheng, Qiaohua
A1 Qiao, Yanning
A1 Liu, Yihui
A1 Han, Jing
A1 Ren, Wei
A1 Liu, Zhiqiang
YR 2022
UL http://www.eneuro.org/content/9/3/ENEURO.0487-21.2022.abstract
AB The endogenous opioid system plays a crucial role in stress-induced analgesia. Mu-opioid receptors (MORs), one of the major opioid receptors, are expressed widely in subpopulations of cells throughout the CNS. However, the potential roles of MORs expressed in glutamatergic (MORGlut) and γ-aminobutyric acidergic (MORGABA) neurons in stress-induced analgesia remain unclear. By examining tail-flick latencies to noxious radiant heat of male mice, here we investigated the contributions of MORGABA and MORGlut 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 release. Selective deletion of MORGABA but not MORGlut 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 MORGlut 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 MORGABA exerts analgesia, whereas MORGlut produces antianalgesia. More importantly, with an increase of stress intensities, the efficiencies of MORs on nociception shifts from balance between MORGlut and MORGABA to biasing toward MORGABA-mediated processes. Our results point to the cellular dynamic characteristics of MORs expressed in excitatory and inhibitory neurons in pain modulation under various stress intensities.