Why, and how, do we feel pain?

I’m sure you’ve experienced pain in some form or another, whether it be physically or emotionally. In this article you will understand why you need to feel this unpleasant sensation and how the brain interprets and recognises pain. 

According to the IASP, “Pain is an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage.”¹ This definition embodies and explains just how complex and intricate pain is; it is subjective and personally shaped by biological, psychological, cultural, and social factors. 

Our brain is the ultimate interpreter for the perception (conscious experience) of pain, primarily through nociception. This physiological process uses pain receptors (nociceptors) to detect harmful stimuli and then translates them into pain.² 

Why is this important? Acute pain, which is short-lasting, helps keep you safe from harm that you know is coming. For example, when a hot pot touches your hand or you hit your leg on an iron rod. This can also be described as nociceptive pain, which is the type of pain you will mostly experience on a daily basis. But when acute pain turns into chronic pain, it adds to the problems of not getting enough care, opioid abuse, and addiction.³ 

Essentially, pain can be both protective and destructive. Understanding the way your brain interprets pain from its transmission to perception is very important for getting better results from care and making people with pain conditions happier with their lives.

What triggers pain?

Pain generally starts when the body senses an internal or external stimuli. Some of these are: 

• Mechanical stimuli like cuts, pressure, or injury
• Thermal stimuli such as extreme heat or cold
• Chemical stimuli from substances released during tissue damage or inflammation⁴

The skin, joints, muscles, and organs all have nociceptors, which are special nerve endings that are activated by these harmful impulses. As a part of daily life, people go to the hospital after getting hurt by high heat, extreme cold, strong mechanical force, or exposure to harmful chemicals.⁵ You only know you have been hurt because your body has nociceptors all over it. 

The nerve highway: how do the signals travel?

Now that you have an understanding of nociception as the primary mechanism for pain signaling through nociceptors, let's delve a little deeper into how it all works. Here, you will understand how pain is transduced and transmitted.

When physical pain is exerted on any part of your body, these nociceptors are all over and send signals from the injury site to the spinal cord through specific sensory neurons called the primary afferent neurons; they are the first order of neurons in the pain pathway.⁶ 

They are like special reporters of what is happening regarding pain in the body, sending reports to the central nervous system (brain & spinal cord). There are two types: A-delta (fast, sharp pain), transmitting pain due to injuries like cuts, electricity shocks, or hits to the body, and C fibers (slow, dull pain), conveying pulsating, slow, and fleeting pain.⁶ 

This report is dropped at a conveying point behind the spinal cord called the dorsal root ganglion (DRG). This serves as the checkpoint that sorts information carried to the brain.⁶

This process is called pain transduction. It explains how painful mechanical stimuli are transformed into electrical signals or action potentials. These signals will be transported to the spinal cord and transmitted through first, second, and third-order neurons.⁷ 

Think of it like when you're travelling and you have connecting flights that eventually lead you to your final destination. For pain, your first to third order of neurons are the connecting flights that send pain signals to the final destination, the brain. This explains the transmission process of pain.

From the DRG, these first-order neurons enter the spinal cord to make a connection called a synapse with the second-order neurons specific for a particular type of pain. From the second neurons, I am sure you have guessed, they will transmit signals to the third neurons over the synapse. The third neuron then sends the signal to the thalamus of the brain, and these signals are processed and sent to different parts of the brain for interpretation.⁸

Spinal cord integration and relay

Now that you know how pain is transduced from the nerve cells that detect the pain causing noxious stimuli to the neurons that transmit the signals in the spinal cord, what you need to know is that these signals are not just passing through. They get fine-tuned by amplifying or reducing the pain signals as they ascend to the brain. This is called pain modulation.⁸

How does this happen? There are different areas where the pain can be modulated: the nerve cell, the spinal cord, and the brain.

In the spinal cord, the Gate Control Theory explains how pain is modulated. That's why rubbing an area that hurts can make it feel better. The spinal cord is like a "gate" that controls how much information about pain gets to the brain.⁹ When you touch or rub the skin, A-beta fibres are triggered. These are the nerve fibres that don't hurt, or rather respond to stimuli such as touch or pressure. You can feel less pain when these fibres close the gate.

The brain's role: from signal to perception

The perception of pain involves a very complex interplay between different brain structures and cortices. The way each person feels pain is based on the activity of the "pain matrix," which is a term for the different parts and networks of the brain that are activated during nociception. This means there isn't one specific site or cortex in the brain that interprets pain perception, unlike some other senses. These areas include:

Thalamus, the relay station of the brain 

It is the main part of the brain that handles data from third-order neurons and projects them to the cerebral cortex. It directs and puts in order which pain signals go to various parts of the brain.^8,9

Somatosensory cortex

The primary somatosensory cortex helps you feel pain in a way that alerts you to recognize the pain.¹⁰ This area of the brain receives stimuli that are not painful and stimuli that are painful; therefore, it is at this junction that either of these stimuli can be heightened to cause the feeling of pain that you are aware of.¹¹

Limbic system 

The limbic system helps you to handle how you feel and express pain. It combines the mental and emotional aspects of pain. The main components involved in this are the amygdala and anterior cingulate cortex(ACC). The ACC helps with the emotional side of pain; it affects how you feel when you are hurt by connecting with different areas in the brain.¹² 

The amygdala processes sensory input and combines pain-related information, playing a role in both making pain worse and stopping it. It does so by changing the connections between neurons (synaptic plasticity).¹³

Prefrontal cortex

The prefrontal cortex (PFC) is also a key part of how pain can be modulated and handled. This part of the brain is crucial for decision-making, and so it influences how pain is perceived in different ways. Below are the two major ways that this happens: 

How the PFC changes pain

• It can reduce pain, but it may also make chronic pain worse through corticostriatal pathways that are affected by dopamine levels

Pain processing based on context

• When pain is under control, the dorsolateral PFC (dlPFC) helps stop you from feeling pain
• The medial prefrontal cortex (mPFC), on the other hand, makes more connections with pain-processing areas when pain is out of control, which can make your pain feel worse
• More pain sensitivity is related to less activity in the dlPFC. This shows how important attention and cognitive control are in shaping pain feelings^14,15,16

How can pain be managed?

Understanding the mechanism of pain from nociception to perception helps individuals find the best therapy suitable to manage pain. 

There are different approaches to alleviate pain, some of which include:

• Medications like NSAIDs 
• Cognitive-behavioral therapy
• Mindfulness and exercise: see ten ways to reduce pain 
• Neuromodulation i.e TENS¹⁷

Do not forget to consult with your healthcare provider, who will suggest the best method for you. 

Summary

The experience of pain, from damage to the surface of your skin to its processing and interpretation in the brain, is both subjective and complex. It involves different brain regions that compute and integrate experience, social interaction, and cognition into pain modulation for perception.

• Nociceptor nerve endings are found in the skin, muscles, joints, and organs and are activated by harmful mechanical, thermal, or chemical stimulation
• First, second, and third-order neurons make up a route that pain signals follow from the injury spot to the spinal cord and finally to the brain
• In the brain and spinal cord, pain can get worse or better
• Acute pain keeps you safe, but chronic pain can get in the way of life and needs to be carefully managed
• Knowing how pain works lets you make personalised treatment plans that may include drugs, cognitive-behavioral therapy, awareness, and neuromodulation methods like TENS