Itch is a protective sensation producing a desire to scratch. Pathologic itch can be a chronic symptom of illnesses such as uremia, cholestatic liver disease, neuropathies and dermatitis, however current therapeutic options are limited. Many types of cell surface receptors, including those present on cells in the skin, on sensory neurons and on neurons in the spinal cord, have been implicated in itch signaling. The role of G protein signaling in the regulation of pruriception is poorly understood. We identify here two G protein signaling components whose mutation impairs itch sensation. R7bp (a.k.a. Rgs7bp) is a palmitoylated membrane anchoring protein expressed in neurons that facilitates Gαi/o -directed GTPase activating protein activity mediated by the Gβ5/R7-RGS complex. Knockout of R7bp diminishes scratching responses to multiple cutaneously applied and intrathecally-administered pruritogens in mice. Knock-in to mice of a GTPase activating protein-insensitive mutant of Gαo (Gnao1 G184S/+) produces a similar pruriceptive phenotype. The pruriceptive defect in R7bp knockout mice was rescued in double knockout mice also lacking Oprk1, encoding the G protein-coupled kappa-opioid receptor whose activation is known to inhibit itch sensation. In a model of atopic dermatitis (eczema), R7bp knockout mice showed diminished scratching behavior and enhanced sensitivity to kappa opioid agonists. Taken together, our results indicate that R7bp is a key regulator of itch sensation and suggest the potential targeting of R7bp-dependent GTPase activating protein activity as a novel therapeutic strategy for pathological itch.

In addition to physical symptoms and treatment burden, people affected by serious illness experience psychological, social, and spiritual distress. Medical professionals who care for them, including psychiatrists and other mental health clinicians, attend to these multiple dimensions of suffering with the hope and promise of improving patients' quality of life. Yet anxiety, depression, adjustment disorder, and existential distress often prove resistant to existing medical or behavioral interventions. A growing body of evidence suggests the safety and efficacy of psychedelic-assisted therapies (PATs) to improve these outcomes. As societal norms around the stigma of psychedelic agents shift, there is an increasing interest in integrating these treatment modalities into serious illness care. To promote awareness among mental health professionals, this article describes aspects of serious illness care that might be amenable to PATs, reviews the evidence documenting the safety and efficacy of PATs in serious illness care, and highlights some of the opportunities and challenges moving forward. [ Psychiatr Ann. 2022;52(9):359–364.]