Pain Spreads

Why does pain spread?

We all know that an injury hurts. Imagine pricking yourself with a tack. The site of injury (the pin prick) will hurt, but so will the area around it. What is that? And why does that happen?

Scientists have a name for this; hyperalgesia. And there are two types. Primary hyperalgesia refers to higher sensitivity to pain in the area immediately surrounding the injury. Imagine the red inflammation that surrounds the pin prick. Secondary hyperalgesia is even more expansive, and lasts longer.

So how does this happen? Does local inflammation makes pain-sensing neurons more sensitive? Or do the neurons that detect pain somehow communicate with the brain and tell the brain to make the surrounding area more sensitive?

Do primary and secondary hyperalgesia happen independently of the brain? Or is the brain necessary for this to happen? We can't know just by thinking about it. We need to do an experiment.

In neuroscience, if we want to know if "a" is necessary for "b", we would try to get to "b" without using "a." If we can get the effect without the condition "a," then we can say "a" is not necessary for "b". To test if water is necessary for a plant to grow, we would see if the plant can grow without water. If the plants cannot grow without water, we'd say that water is necessary for plant growth. To determine if the brain is necessary to primary or secondary hyperalgesia, we would try to see if those phenomena can occur without the brain. If hyperalgesia can occur without the injured tissue communicating with the brain, then hyperalgesia happens independently of brain input. Simple enough.

But how can we separate the site of injury from the brain? Lidocaine!

Lidocaine is a drug that prevents neurons from sending electrical signals to the brain. Doctors classify it as a "local anesthetic" because it inhibits pain locally, at the site of injection. So if we blocks neuronal signals to the brain with lidocaine, we can see if hyperalgesia can happen at the site of injury without the brain knowing that injury has occurred. Clever, huh?

Let's look at figure a above. The x is where a painful chemical was injected into the forearm. The grayed out region is the part of the forearm numbed by lidocaine. Remember, lidocaine blocks neuronal communcation with the brain, so sensory regions of the brain know nothing of the injury. And yet, we still see red flare and inflammation around the site of injection (the dashed circle). Primary hyperalgesia can occur independently of the brain.

Now let's look at figure B. Here, lidocaine is not injected with the painful chemical. Within minutes of injury, we see a small region of red flare around the site of injury, but also a larger region of pain sensitivity (dotted and solid regions). Without lidocaine, we see primary AND secondary hyperalgesia. With lidocaine, we only see primary hyperalgesia.

So what can we conclude from this experiment? We would say that primary hyperalgesia does not require pain-sensing neurons in the forearm to communicate with the brain. But the brain is required for secondary hyperalgesia to occur, because we only say secondary hyperalgesia happen when pain-sensing neurons in the forearm were able to communicate with the brain. Somehow, local inflammation or sensations mediate the red flare and pain sensitivity in the area immediately around the site of injury. But the wider, more expansive pain sensitivity does require brain input to the site of injury.

Back to the original question: Why does pain spread? Molecules and cells around the site of injury respond by making pain-sensing neurons more sensitive. We call this peripheral sensitization. Neurons surrounding this primary site of injury become more sensitive by some input from the brain. We call this central sensitization, because these neurons require central input.

Generally, this heightened sensitivity to pain, following injury protects the wound. It makes us more aware of the healing wound, so that we don't subject it to further damage. So next time you burn yourself or stub your toe, be grateful that these amazingly complex mechanisms are working properly.

Let me know if you want me to write a follow-up about the specifics of peripheral and central sensitization.