Scientists Find Brain Cells That Make Pain Hurt – by Jonathan Lambert – Jan 2019
Pain is a complicated experience. Our skin and muscles sense it, just like they sense softness or warmth. But unlike other sensations, the experience of pain is distinctly unpleasant.
Pain has to hurt for us to pay attention to it, and avoid hurting ourselves further. But for people in chronic pain, the pain has largely lost its purpose. It just hurts.
This “pain without cause” is incredibly frustrating to deal with. Often, no one else can believe you’re really hurting. Sometimes it’s driven me to the point of thinking I must be crazy because I felt pain “for no reason”.
While it has long been understood how nerves signal pain to the brain, scientists haven’t known how the brain adds a layer of unpleasantness.
A research team from Stanford University pinpointed the neurons in mouse brains that make pain hurt and were able to alter these neurons in a way that reduced the unpleasantness of pain without eliminating the sensation.
That truly is the “holy grail” of pain medication. We don’t want to stop feeling any pain warning when we lean on a hot stove, but we don’t want to have pain that continues without such a specific reason.
Stanford neuroscientist Grégory Scherrer, who co-led the study, started the search for pain neurons in the amygdala — the slim, almond-shaped region scientists know regulates many emotions.
The amygdala is often referred to as the “lizard brain” because it’s an ancient evolutionary leftover that’s relatively primitive, yet extremely powerful (and disruptive of reasoning).
For better or worse, it responds to sensory input much faster than the “thinking part” of our brains and send us into intense emotions, such as panic, and physical reactions, like running away, before we can even figure out what’s happening and think of a more rational response.
The challenge for Scherrer was to sift through the tangle of neurons there and identify the ones associated with pain.
To do this he teamed up with his Stanford colleague Mark Schnitzer, a neuroscientist who developed a miniature microscope, or miniscope, that can be attached to the head of a freely behaving mouse.
“The miniscope allows you to track neurons over time while the mouse is behaving normally,” says Schnitzer.
When a mouse is in pain it reflexively withdraws, just as our hand does when we touch a hot stove. Scherrer says that these reflexive behaviors indicate the sensation of pain, but aren’t unpleasant.
Other behaviors, like avoiding the painful stimulus, or licking the paw that touched it, indicate that the pain is unpleasant.
The researchers exposed the mice to a variety of painful and benign stimuli, and identified a constellation of about 150 neurons in a region called the basolateral amygdala that were active only when the mice appeared to be in pain. Further, it seemed that the more pain the mouse experienced, the brighter this constellation in the BLA glowed.
Scherrer and his team created chemical switches to control these pain neurons. They could then switch these pain neurons off, and see if a mouse behaved differently when pricked.
With the switches in place, the researchers turned off the BLA pain neurons, and found that the mice still sensed pain, but they didn’t behave as though it were unpleasant.
This result held up when the researchers looked at mice who had developed chronic pain. Their BLA pain neurons had become so sensitive that they fired at the lightest touch.
This is hyperalgesia: increased sensitivity to painful stimuli.
When Scherrer turned off their BLA pain neurons, the mice still experienced the light touch, but didn’t seem to experience it as unpleasant.
“This result got us really excited,” says Scherrer, explaining that their results suggest that the unpleasantness of both acute and chronic pain stem from these BLA pain neurons, making them a target for treating pain.
If there are receptors unique to these neurons, researchers could try to design drugs that turn down their activity. If the approach worked, it could lead to a drug that makes pain more bearable, but doesn’t dull sensation, according to Schnitzer.
A treatment like that is a long way off, even under the best of circumstances.
While this research confirms the BLA neurons play a critical role in making pain hurt, they could be working in concert with other brain areas that would need to be understood. Scherrer and his colleagues are working to trace those connections for a fuller picture.
Jonathan Lambert is an intern on NPR’s Science Desk. You can follow him on Twitter: @evolambert.
In biologically complex animals, there’s always more to it than just a handful of identifiable neurons. While the first research into biological mechanisms often finds some clear correlations, these often turn out to be just the most obvious drivers.
Only as research progresses and looks into the multiple biological control processes involved do we see the complexity of trying to control it because our bodies have so many processes, all working together, which both raise and lower the amounts of any single substance to maintain homeostasis.