SUMMARY Why do opiates make human beings itch ? Spinal opioid-induced itch, a prevalent side effect of pain management, has been considered to occur as a result of pain inhibition. We report that morphine-induced scratching (MIS) is abolished in mice lacking either gastrin-releasing peptide receptor (GRPR) or the μ opioid receptor (MOR). Using exon-specific knockdown, we identified the MOR1D isoform as essential for MIS, whereas MOR1 is important for morphine-induced analgesia (MIA) with no cross activity present. MOR1D and GRPR form constitutive heterodimers in the spinal cord and relay itch information upon morphine activation. Morphine induces internalization of both GRPR and MOR1D, whereas GRP induces that of GRPR but not MOR1D, when co-expressed. Moreover, GRP-induced scratching (GIS) is independent of MOR activation. These results suggest a unidirectional cross-activation of GRPR signaling by MOR1D via heterodimerization, and that opioid-induced itch is an active process concomitant with but independent of opioid analgesia.

ObjectivesTo assess the magnitude of mental health outcomes and associated factors among psychiatric professionals in mental health services during COVID-19 in China.Design, setting and participantsThis cross-sectional, survey-based, region-stratified study collected demographic data and mental health measurements from psychiatric professionals in 34 hospitals between 29 January and 7 February 2020, in China. Hospitals equipped with fever clinics or deployed on wards for patients with COVID-19 were eligible.Primary outcome and measuresThe severity of symptoms of depression, anxiety, insomnia and distress were assessed by the Chinese versions of 9-item Patient Health Questionnaire, 7-item Generalised Anxiety Disorder, 7-item Insomnia Severity Index and 22-item Impact of Event Scale-Revised, respectively. Multivariable logistic regression and structural equation modelling was performed to identify factors associated with mental health outcomes.ResultsA total of 610 psychiatric professionals were included. 29.8% were employed in Wuhan, and 22.5% were frontline workers. A considerable proportion of participants reported symptoms of depression (461 (75.6%)), anxiety (282 (46.2%)), insomnia (336 (55.1%)) and mental stress (481 (78.9%)). Psychiatric symptoms were associated with worrying about infection (eg, OR 2.36 (95% CI 1.27 to 4.39) for anxiety), risks of exposure to COVID-19 (eg, having inadequate personal protection equipment, OR 2.43 (1.32 to 4.47) for depression) and self-perceived physical health (eg, OR 3.22 (2.24 to 4.64) for mental stress). Information sources of COVID-19 were also found to be both positively (eg, information from relatives, OR 2.16 (1.46 to 3.21) for mental stress) and negatively (eg, information from TV, OR 0.52 (0.35 to 0.77) for mental stress) associated with mental stress. There is preliminary evidence that mental health might benefit from greater availability of mental healthcare services. The structural equation model analysis indicated that worrying about infection may be the primary mediator via which risk of exposure to COVID-19 pandemic affects the mental health of psychiatric professionals.ConclusionsThe current findings demonstrate several pathways via which the COVID-19 pandemic may have negatively affected the mental health of psychiatric professionals in China.