https://www.science.org/doi/10.1126/science.ado6593
Fatt et al, Science Vol 385, Issue 6712 (Aug 30, 2024)
Patrik Ernfors’ Lab
Editor’s summary
It has been known for decades that a brainstem area called the rostral ventromedial medulla is important for opioid-induced analgesia, but the neural substrates underlying this phenomenon have remained elusive. Through the application of mouse genetics and the manipulation of neuron activity with engineered viruses, Fatt et al. discovered that a single type of excitatory neuron located in this brain region confers morphine antinociception (see the Perspective by De Preter and Heinricher). These neurons project to the spinal cord, where, through monosynaptic connectivity, they activate a defined inhibitory spinal neuron type that gates pain signaling in the ascending pain pathway. Inhibition of either the excitatory neurons in the rostral ventromedial medulla or the inhibitory neurons in the spinal cord was found to abolish all of the analgesic effects of systemically administered morphine. —Peter Stern