The authors discovered that training mice to exhibit a placebo effect with one type of pain produces marked relief of several different types of pain, including pain caused by injury.
To establish that the native opioid peptides actually drive pain relief, similar to opioid painkillers such as morphine, the researchers employed a light-activated drug developed in Banghart’s lab called PhNX, for photoactivatable naloxone. Naloxone, also known as Narcan, is the medicine used to reverse opioid overdoses by blocking opioid receptors. Using light, they were able to precisely control the site and timing of opioid signaling interference. Using PhNX, the scienists found that both morphine-induced pain relief and placebo pain relief rely on opioid signaling in the vlPAG brain region.
Co-first author: “We essentially trained a mouse brain to create its own broad-spectrum painkillers on demand, precisely where they are needed to treat pain, without the off-target effects of opioid-based painkillers.”
“These results increase the translational relevance of rodent placebo models to clinical contexts, in which patients’ prior experiences with drugs and treatment settings can generalize to broader expectations of improvement,” the researchers conclude in their paper. ScienceMission sciencenewshighlights.
Placebo effects, in which patients experience relief without therapeutic treatment, increasingly have been considered as potentially powerful clinical treatments for ailments such as depression and pain. Yet the neurological mechanisms underlying such processes are not fully understood.
Now, a multi-institutional team has pinpointed the brain circuitry responsible for placebo pain relief. Their findings, reported in the journal Neuron, describe brain regions that support placebo effects and identify sites where endogenous opioid neuropeptides (commonly referred to as endorphins) provide signals that are critical for placebo pain relief.
