THE SCIENCE OF PAIN

Our internal alarm system works around the clock to keep us safe from harm.

Millions of sensitive nerves guard our tissues, listening for physical danger. These pain sensors, or nociceptors, detect temperature, pressure and chemical signals. They have a high threshold for activation and only send messages when the body is at risk of harm.

If skin temperature rises above 40 degrees Celsius or dips below 15 degrees Celsius, thermal nociceptors start to fire. If pressure exceeds three kilograms per centimetre squared, or if the skin stretches or tears, mechano-nociceptors kick into action. And if cells become damaged and start leaking their contents, chemical nociceptors switch on.

A rapid response to nociceptor activation is crucial. If you put your hand in a flame, your body needs to react in fractions of a second. Nociceptors send their signals to the spinal cord, which manages the first step of the response. It can process some of the information without the brain, triggering a rapid withdrawal reflex. This is the very simplest form of damage control, and even primitive animals sense and respond to harm in this way. But pain is more than just a reflex.

As the hand pulls away from the fire, the signal from the nociceptors passes up the spinal cord towards the brainstem. In the brain it enters the cerebral cortex, responsible for cognition and consciousness. Processing here ties the incoming sensory signals to memory and emotion, producing the complex feeling of pain. The unpleasant experience that follows helps us to remember harmful activities and to avoid them in the future.

Killing Pain

Damage to our tissues causes mechanical and chemical changes that activate pain-sensing neurons. The neurons send signals to the spinal cord, which relays them to the brain. Painkillers try to block this process by interfering with it at different stages.

The most common over-the-counter painkillers attack the very start of the pain-sensing chain. Non-steroidal anti-inflammatory drugs (NSAIDs) – like ibuprofen – try to remove some of the chemical signals that activate pain-sensing neurons. They do this by interfering with an enzyme called cyclooxygenase (COX). COX makes chemical messengers called prostaglandins, which promote inflammation. Blocking COX dampens the inflammatory response, relieving the pain.

The next step in the pathway is the transmission of pain signals towards the spinal cord. Local anaesthetics work here. For nerve cells to fire they need to transport sodium ions across their membranes. These carry a charge, which sets up the electrical signal. Local anaesthetics block the channels that transport the ions, stopping pain signals in their tracks.

The strongest painkillers, the opioids, work on the next part of the pathway: preventing signals getting to the brain. This group includes codeine, morphine and the illegal drug heroin. They act on the spinal cord and brainstem to stop pain messages passing through.

Finally, there are the general anaesthetics, which work on the very last link in the chain. They stop the brain being aware of pain by interfering with the way that nerve cells pass signals to each other. Each kind of painkiller has advantages and disadvantages for di erent situations.

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The Different Types of Pain

Pain can be short-term (acute) or long-term (chronic). It can be mild, uncomfortable, distressing or debilitating. It can feel achy, dull, raw, sharp, stabbing, throbbing or burning. It might be constant or it might come and go. But beneath these different experiences, all pain falls into two main categories: nociceptive and neuropathic.

Nociceptive pain is the normal response to tissue damage. Pain nerves sense extreme temperature, extreme pressure or harmful chemicals and they send signals to the brain. This alerts us to danger, encourages us to rest the injured area and reminds us to avoid the situation in the future.

Neuropathic pain, by contrast, does not serve a useful purpose. It is the result of nerve damage. Certain injuries, illnesses and infections harm pain-sensing neurons, and if the body cannot make repairs, they can start to misfire. The nerves send pain signals when there shouldn’t be any pain, and the brain can’t tell the difference. This type of pain is particularly challenging to treat.

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Treating Chronic Pain

Over-the-counter painkillers tend to target inflammation, which means they are not always particularly useful for chronic pain. Opiate painkillers, like codeine and morphine, can stop pain messages reaching the brain, but they are addictive and their effectiveness decreases over time, so they are not recommended for long-term treatment. Other options include antidepressants and anticonvulsants; these actually change the brain’s chemistry, but they don’t work for everyone.

The pharmaceutical industry has been looking at a chemical produced by the brain called nerve growth factor (NGF). NGF changes the pain sensitivity of nerves, and blocking its activity in animals has been shown to help to reduce pain, but trials conducted in humans in 2010 had dangerous side-effects, including loss of blood to the bones. There is still a lot of work to do to find out whether they are safe to use.

Physical and psychological therapy can help to provide some distraction, but many people struggle daily with chronic pain. Without a cause for doctors to treat, it can be extremely hard to manage.

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People Who Don’t Feel Pain

Very rarely, people are born without the ability to feel pain. A defect in a gene called SCN9A makes it impossible for their pain-sensing nerve cells to transmit signals. This makes it impossible for them to tell when hot becomes burning, when cold becomes freezing or when pressure becomes crushing.

The SCN9A gene codes for a protein that makes a part of a structure called a sodium channel. Sodium ions carry the electrical signals along nerves, and these channels control their movement. With the mutation in the gene, the channels don’t fit together and the pain-sensing neurons can’t fire. While this might sound like a superpower, but being unable to sense pain makes people with these genetic faults much more likely to do themselves harm.

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Gate Control Theory

Have you ever stubbed your toe and immediately reached down to grab your foot? Or burnt your finger and instinctively put it into your mouth? This is gate control theory at work.

Pain signals travel from the site of an injury towards your brain along thin nerve fibres. As they enter the spinal cord they compete for bandwidth with the other nerves that are also trying to send messages to your brain. This includes larger fibres that carry non-painful signals, like pressure and touch. Both the painful and non-painful signals are trying to reach the projection cells of the spinal cord, but there’s a gatekeeper in the way.

The gatekeeper is an inhibitory neuron. It listens for signals from both the pain fibres and the sensory fibres and decides which can send its signals to the projection neuron. When a pain signal arrives on its own the interneuron lets it through the gate, but when a sensory signal is passing the gate the pain signal closes. So if you put pressure on your stubbed toe it can stop some of the pain signals from reaching your brain, naturally blocking out the unpleasant feeling.

By Laura Mears in "How It Works", UK, issue 116, 2018, excerpts pp. 30-35. Digitized, adapted and illustrated to be posted by Leopoldo Costa