Opioids have distributed effects on the brainstem circuitry that controls breathing, including presynaptic and postsynaptic receptor-mediated inhibition of an excitatory circuit from the dorsolateral pons to the ventrolateral medulla.
Exogenous opioid analgesia is mediated by MORs expressed in glutamatergic neurons, whereas endogenous opioid analgesia is mediated by MORs expressed in GABAergic neurons.
Sina B Kirchhofer, Victor Jun Yu Lim ... Moritz Bünemann
The molecular pattern underlying the interactions of opioids with their receptor determines whether membrane depolarization increases or decreases their response or even convert antagonists to agonists.
The structure-based design established a new approach to control pathway-selective activation of opioid receptors, resulting in new dual MOR/KOR G-protein biased agonist analgesics with attenuated liabilities.
Inspiratory rhythmogenesis is mediated by an emergent mechanism independent of bursts associated with motor output and is modulated by opioids, pointing to strategies for ameliorating opioid-induced respiratory depression.
The naturally occurring biologics, FLO and HC-HA/PTX3, derived from human birth tissues, may be developed as a much-needed non-opioid therapy for post-surgical pain treatment, leveraging robust neuronal mechanisms.
Xinyi Jenny He, Janki Patel ... Matthew R Banghart
Mu and delta opioid receptors signal independently in hippocampal parvalbumin interneurons to regulate somato-dendritic excitability and synaptic transmission, with the delta opioid receptor dominating the response to enkephalin.
Sara González-Rodríguez, Mohiuddin A Quadir ... Christoph Stein
A novel opioid formulation producing analgesia similar to conventional opioids without permeation of blood-brain or intestinal barriers, thus precluding sedation, constipation and respiratory depression.
