What Is Nociceptive Pain?

Pain is an essential means of communication our bodies use to help signal to us that there may be an underlying health issue compromising our well-being. Therefore, pain perception is a crucial mechanism for survival. Nociceptive pain, in particular, is a term used to describe sharp, dull or throbbing pain and arises in response to harmful signals or stimuli, often also referred to as “noxious” stimuli. Examples of noxious stimuli include pressure, heat, cold or chemical triggers that may lead to tissue damage or injury. This harmful stimulus is then detected by receptors in our body named nociceptors, which are connected to nerve endings found predominantly in our skin, joints, muscles and internal organs. Nociceptors are designed to send electrical signals to our brain, alerting it that the body is experiencing a potential threat; therefore, an immediate response that moves the body away from the source of pain is required. Examples of nociceptive pain that most people have encountered in their lives include the experience of a toothache or a burn while cooking. 

Types of nociceptive pain

There are two main types of nociceptive pain: somatic nociceptive pain and visceral nociceptive pain.

Somatic nociceptive pain refers to the pain detection in superficial areas of the body, such as your skin, bones, muscles and joints, and can often be referred to as musculoskeletal pain. Somatic pain is characterised by sharp or aching pain and is experienced as an immediate and intense form of pain. The nature of somatic pain is typically transient therefore, it is not permanent and is associated with a specific, localised point on the body where your brain detects and processes pain. This is the kind of pain we feel when we get cuts, broken bones, or injure our muscles and joints. 

Examples of conditions that cause somatic nociceptive pain: 

• Bone fractures 
• Arthritis (swelling of joints)
• Teeth cavities 
• Tendonitis

On the other hand, visceral nociceptive pain is described as pain arising from nociceptors located on areas deeper within your body, such as internal organs (stomach, intestines, heart, etc.), or blood vessels, and the pain sensation differs greatly from that experienced in the somatic nervous system. Visceral pain is often associated with a feeling of nausea and disruptions in the digestive system and can cause sweating, changes in body temperature and blood pressure, or a combination. Unlike somatic pain, it is much more difficult to identify the region in the body causing these feelings of pain. Visceral pain often radiates to different areas of the body, which are also more internalised and, therefore, less accessible, resulting in a more generalised, dull and vague experience of pain. This is described as “referred” pain in scientific literature and implies that the pain sensation differs depending on the site where the noxious stimuli have triggered tissue damage within the body.¹ 

Examples of conditions that elicit visceral nociceptive pain: 

• Gastritis
• Kidney stones 
• Appendicitis
• Endometriosis
• Irritable bowel syndrome

Mechanisms of nociceptive pain

Nociceptors are nerve endings that are responsible for the sensation of pain, a process described as nociception. When the body is subjected to noxious stimuli, nociceptors detect this trigger and send an electrical impulse (an action potential) along the nerve axon (a long structure within a nerve cell that looks like a nerve tail). This signal eventually reaches the spinal cord or the brain stem, where it then reaches a brain region named the thalamus. Depending on the nature of the pain, the thalamus can direct the pain signal to the appropriate region of your brain, where it is processed. For instance, if you experience a cut in your hands, your nerves will signal the transmission of an electrical impulse towards your thalamus, which would then direct the impulse to the somatosensory cortex. There, the impulse would be processed by the brain, causing the pain to be sensed by the individual.^2,3 (fig 1) 

There are various types of nociceptors, including mechanoreceptors (respond to mechanical stimuli and pressure), thermoreceptors (respond to changes in temperature) and polymodal nociceptors (respond to multiple kinds of stimuli), and are designed to help the brain and your body distinguish between the various forms of noxious stimuli. Within these receptor subtypes, nociceptors are further distinguished depending on the properties of the axon they are connected to. For instance, Aδ nociceptors are connected to myelinated axons (axons surrounded by a myelin sheath, a material which speeds up the transmission of the electrical impulse), which transmit information with an approximate conduction speed of 30m/s. These specific nociceptor fibres detect and transmit “primary pain”, a type of pain which is felt momentarily but is still intense. They are further divided into two subtype categories, the type I A_δ and type II A_δ fibres. Type I A_δ fibres are designed to have a high tolerance for elevated temperatures, making them suited to detecting mechanical noxious stimuli only, while type II A_δ fibres can tolerate mechanical pressure well and are thus able to effectively detect and transmit electrical signals that alert the brain about significant changes in thermal noxious stimuli.2,4,5 Similarly, the nociceptive system is also comprised of a type-C fibre nociceptor subtype, which is connected to an unmyelinated neuron (nerve cell) with a signal transmission velocity of approximately 2m/s - much slower than the myelinated neurons that were described above. These fibres are specifically designed to signal “secondary pain”, the type of pain which is duller and achier. These C-fibre nociceptors are further divided into two sub-categories: peptidergic nociceptors, which recognise prolonged thermal stimuli, such as burning, and non-peptidergic nociceptors, which detect mechanical stimuli. Each of these receptor types is distinguished based on the expression of neuropeptides, which are chemical messengers associated with the nervous system network.^2,4 

Pain pathways 

Pain perception is facilitated through two essential pathways within the peripheral nervous system: ascending and descending pathways. 

The ascending pathway 

When the body experiences an injury or harm due to the action of noxious stimuli, nociceptors detect this, whereas cells in the surrounding area become damaged, causing inflammation and the release of prostaglandins, hormone-like lipids that are involved in the biochemical signalling process of inflammation, which further sensitises the nociceptors.⁶ The combination of these biological responses propagates an electrical impulse within the sensory nerve fibres connected to a first-order neuron.^3,7 Neurons of this type will relay this electrical impulse to a second-order neuron passing through the dorsal horn – a region in the spinal cord.8 The second-order neurons will continue to ascend through the spinothalamic tract within the spinal cord, heading towards the thalamus (see fig 1).

The thalamus is the area of the brain that distinguishes signals and, in a way, organises them, directing them to the appropriate brain region, where they are processed. The second-order neurons form synapses (connections) in the thalamus, transmitting the electrical impulse to a third-order neuron. These types of neurons carry the signal to the precise area within the somatosensory cortex, which correlates with the body region where the injury, and therefore the origin of the nociceptive stimulus, has occurred. The somatosensory cortex recognises the exact site of injury, which is processed on the side of the brain that is opposite to the side of the body where the injury happened,  enabling pain perception. The ascending pathway is responsible for transmitting the pain signal to the brain, while the descending pathway, which we will talk about now, modulates and controls the ascending pathway in its effort to inhibit the signalling process of the ascending pathway. 

The descending pathway

In the descending pathway, neurons in the midbrain that emerge from a region named the periaqueductal grey matter send signals down to a secondary neuron within the medulla oblongata, in a region called the nucleus raphe magnus.^9,10 This secondary neuron travels down the spinal cord towards the dorsal horn, where the initial pain signalling occurs in the ascending pathway, as mentioned above. This neuron releases chemical signals which control the signal transmission between the first-order and second-order neurons within the ascending pathway (see red line in Figure 1) and thus help modulate the pain signal transmission. 

Nociceptive pain disorders and conditions 

The most common medical conditions and pain disorders include arthritis and post-operative pain. 

Arthritis is characterised by joint pain that is caused by chronic inflammation and swelling of the joints. There are various types of arthritis, including osteoarthritis, which is described by swelling caused by wear and tear in the bones, and rheumatoid arthritis, which occurs as a consequence of prolonged and inappropriate activation of the immune system, leading to chronic inflammation.11 Osteoarthritis is most prevalent in elderly patients since bones seem to weaken with age. There is currently no cure for arthritis. However, currently, available therapies include pharmaceutical pain management medication, physiotherapy and exercise, and they can all be effective in managing the symptoms of the disorder.¹² 

Post-operative pain is a type of pain that is caused by surgical trauma that leads to inflammatory responses, as well as due to the body’s natural response to newly formed wounds caused by the operation. This pain is typically acute and subsides after the body undergoes its natural healing processes.¹³

Acute vs chronic nociceptive pain

Acute nociceptive pain is best described as sudden, localised, sharp and intense. It is often reflective of sudden injuries or tissue trauma, and the root cause is mostly easy to identify due to its localised and transient quality. This type of pain is often resolved when its root cause successfully undergoes its healing process. Analgesics (painkiller medications) and anti-inflammatory medications are typically prescribed for acute nociceptive pain episodes. 

On the contrary, chronic pain is often characterised by a persistent discomfort that may be dull and vague. Chronic pain can last for prolonged periods that far exceed the healing duration of the underlying root cause of the pain, meaning people can suffer years of severe ongoing pain despite the site of injury having already healed. Therefore, treatment approaches for chronic pain are often complex and multifaceted approaches are necessitated since the nature of chronic pain arises due to maladaptive alterations made to the nervous system itself. Such alterations impair the system’s ability to accurately process and perceive pain. Consequently, treatment strategies range from pharmaceutical medications, physical therapies and psychological interventions, all aimed at alleviating the pain.¹⁴

Management of nociceptive pain

The current pharmaceutical medication available for nociceptive pain includes local anaesthetics and analgesics, such as paracetamol aspirin, and nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen. Moreover, several studies show that non-pharmaceutical pain management, such as acupuncture, usage of heat/cold compresses, and physical therapy, can also be effective in alleviating pain.^15,16,17,18 

Conclusion

In conclusion, nociceptive pain refers to pain that arises as a result of tissue damage and inflammation that affects our muscles, joints, and organs. It is important to recognise and manage nociceptive pain, as it can compound over time if not addressed quickly enough and is often indicative of a root cause that requires immediate attention and care. Current research on nociceptive pain focuses on studying brain changes that occur in chronic pain patients through a process called neuroplasticity. This type of research aims to understand this process and hopefully develop strategies that rewire the brain of chronic pain patients and restore it to a functional and healthy state.¹⁹ Similarly, emerging research is also exploring the potential efficacy of cannabinoids (CBD and/or THC) as pharmaceutical therapies for pain management.²⁰