It is often said that the path to eternal happiness is not to seek a life without pain, but to learn to be equanimous to pain – or in other words, to just take it on the chin without having a meltdown. Obviously, this is easier said than done, but a new study in the journal Neuron suggests that researchers may have opened the door to new drugs that could help us become more accepting of pain.
Anyone who has ever had a belly ache, a black eye, or a hangover will tell you that you don’t feel particularly motivated to do anything when you’re hurting, and can feel downright miserable. This moody element of pain is caused by the release of a neurotransmitter called dynorphin in a brain region called the nucleus accumbens, which dampens goal-driven behaviors. As a result, people who are in pain become less able to experience pleasure from activities that they normally enjoy.
Researchers at Washington University wanted to see if blocking the effects of dynorphin could eliminate the depressive effects of pain in rats. To do so, they taught the rodents to press a lever in order to receive a sugary reward, before injecting some of them with a substance that caused inflammation in the paw. As expected, these rats became demotivated, and chose to sulk rather than continue to press the lever.
Using a technique called positron emission tomography (PET) imaging, the team discovered that the onset of physical pain caused the dynorphin-containing neurons in a particular section of the nucleus accumbens to become hyper-excited, and that the rats’ demotivation occurred when dynorphin attached to kappa opioid receptors.
When the team administered a compound that blocked the release of dynorphin, however, the rats’ appetite for sugary indulgence returned, and they became motivated once again to press the lever despite still being in pain.
The study authors conclude that the interaction between dynorphin and kappa opioid receptors is the main driver of the emotional response to pain in rats. Clearly much more research is needed in order to confirm if this holds true for humans, but if this does turn out to be the case then we could soon see new lines of painkillers that are designed to provide a big dose of equanimity in the face of anguish.
At present, most prescription painkillers target mu-opioid receptors, dampening the physical sensation of pain and producing an emotional high. This combination of effects can be highly addictive, and is largely responsible for the current opioid crisis and unprecedented number of overdose-related fatalities.
However, future painkillers that target kappa-opioid receptors instead of mu-opioid receptors could enable patients to overcome their aversion to pain, thereby restoring their quality of life via a different route.
Summing up the significance of this research, study author Jose Moron-Concepcion said in a statement that “by targeting the emotional aspects of pain, we hope to make pain less debilitating so that patients won’t crave the emotional high they get from opioids.”
