Pain

In 1995, the British Medical Journal published an astonishing report about a 29-year-old builder. He accidentally jumped onto a 15-centimetre nail, which pierced straight through his steel-toed boot. He was in such agonising pain that even the smallest movement was unbearable. But when the doctors took off his boot, they faced a surprising sight: the nail had never touched his foot at all.

The science of pain

For hundreds of years, scientists thought that pain was a direct response to damage. By that logic, the more severe an injury is, the more pain it should cause.

But as we’ve learnt more about the science of pain, we’ve discovered that pain and tissue damage don’t always go hand in hand, even when the body’s threat signalling mechanisms are fully functioning.

We’re capable of experiencing severe pain out of proportion to an actual injury, and even pain without any injury, like the builder, or the well-documented cases of male partners of pregnant women experiencing pain during the pregnancy or labour.

What’s going on here? There are actually two phenomena at play:

• The experience of pain
• A biological process called nociception.

Nociception

• Nociception is part of the nervous system’s protective response to harmful or potentially harmful stimuli.
• Sensors in specialised nerve endings detect mechanical, thermal, and chemical threats.
• If enough sensors are activated, electrical signals shoot up the nerve to the spine and on to the brain.
• The brain weighs the importance of these signals and produces pain if it decides the body needs protection.
• Typically, pain helps the body avoid further injury or damage.

But there are a whole set of factors besides nociception that can influence the experience of pain, and make pain less useful.

1. First, there are biological factors that amplify nociceptive signals to the brain.

• If nerve fibres are activated repeatedly, the brain may decide they need to be more sensitive to adequately protect the body from threats.
  • More stress sensors can be added to nerve fibres until they become so sensitive that even light touches to the skin spark intense electrical signals.
• In other cases, nerves adapt to send signals more efficiently, amplifying the message.
  • These forms of amplification are most common in people experiencing chronic pain, which is defined as pain lasting more than 3 months.
• When the nervous system is nudged into an ongoing state of high alert, pain can outlast physical injury.
  • This creates a vicious cycle in which the longer pain persists, the more difficult it becomes to reverse.

2. Psychological factors clearly play a role in pain too, potentially by influencing nociception and by influencing the brain directly.

• A person’s emotional state, memories, beliefs about pain and expectations about treatment can all influence how much pain they experience.
• In one study, children who reported believing they had no control over pain actually experienced more intense pain than those who believed they had some control.

3. Features of the environment matter too:

• In one experiment, volunteers with a cold rod placed on the back of their hand reported feeling more pain when they were shown a red light than a blue one, even though the rod was the same temperature each time.

4. Finally, social factors like the availability of family support can affect perception of pain.

• All of this means that a multi-pronged approach to pain treatment that includes pain specialists, physical therapists, clinical psychologists, nurses and other healthcare professionals is often most effective.

We’re only beginning to uncover the mechanisms behind the experience of pain, but there are some promising areas of research.

And genetic testing in people with rare disorders that prevent them from feeling pain has pinpointed several other possible targets for drugs and perhaps eventually gene therapy.

Until recently, we thought the glial cells surrounding neurons were just support structures, but now we know they have a huge role in influencing nociception.

Studies have shown that disabling certain brain circuits in the amygdala can eliminate pain in rats.

Let’s say that it would take you ten minutes to solve this puzzle. How long would it take if you received constant electric shocks to your hands? Longer, right? Because the pain would distract you from the task. Well, maybe not – it depends on how you handle pain.

• Some people are distracted by pain. It takes them longer to complete a task, and they do it less well.
• Other people use tasks to distract themselves from pain, and those people actually do the task faster and better when they’re in pain than when they’re not.
• Some people can just send their mind wandering to distract themselves from pain.

How can different people be subjected to the exact same painful stimulus and yet experience the pain so differently? And why does this matter?

First of all, what is pain?

• Pain is an unpleasant sensory and emotional experience, associated with actual or potential tissue damage.
• Pain is something we experience, so it’s best measured by what you say it is.
• Pain has an intensity – you can describe it on a scale from 0, no pain, to 10, the most pain imaginable.
• But pain also has a character, like sharp, dull, burning, or aching.

What exactly creates these perceptions of pain?

• Well, when you get hurt, special tissue damage-sensing nerve cells, called nociceptors, fire and send signals to the spinal cord and then up to the brain.
• Processing work gets done by cells called neurons and glia. This is your Grey matter.
• And brain superhighways carry information as electrical impulses from one area to another. This is your White matter.
• The superhighway that carries pain information from the spinal cord to the brain is our sensing pathway that ends in the cortex, a part of the brain that decides what to do with the pain signal.
• Another system of interconnected brain cells called the salience network decides what to pay attention to.
  • Since pain can have serious consequences, the pain signal immediately activates the salience network. Now, you’re paying attention.
• The brain also responds to the pain and has to cope with these pain signals.
  • So, motor pathways are activated to take your hand off a hot stove, for example.
• But modulation networks are also activated that deliver endorphins and enkephalins, chemicals released when you’re in pain or during extreme exercise, creating the runner’s high.
• These chemical systems help regulate and reduce pain.

All these networks and pathways work together to create your pain experience, to prevent further tissue damage, and help you to cope with pain.

This system is similar for everyone, but the sensitivity and efficacy of these brain circuits determines how much you feel and cope with pain.

• This is why some people have greater pain than others and why some develop chronic pain that does not respond to treatment, while others respond well.
• Variability in pain sensitivities is not so different than all kinds of variability in responses to other stimuli.
• Like how some people love roller coasters, but other people suffer from terrible motion sickness.

Why does it matter that there is variability in our pain brain circuits?

Well, there are many treatments for pain, targeting different systems.

• For mild pain, non-prescription medications can act on cells where the pain signals start.
• Other stronger pain medicines and anaesthetics work by reducing the activity in pain-sensing circuits or boosting our coping system, or endorphins.
• Some people can cope with pain using methods that involve distraction, relaxation, meditation, yoga, or strategies that can be taught, like cognitive behavioural therapy.
• For some people who suffer from severe chronic pain, that is pain that doesn’t go away months after their injury should have healed, none of the regular treatments work.
• Traditionally, medical science has been about testing treatments on large groups to determine what would help a majority of patients.
  • But this has usually left out some who didn’t benefit from the treatment or experienced side effects.
• Now, new treatments that directly stimulate or block certain pain-sensing attention or modulation networks are being developed, along with ways to tailor them to individual patients, using tools like magnetic resonance imaging to map brain pathways.

Figuring out how your brain responds to pain is the key to finding the best treatment for you. That’s true personalised medicine.