Overview 

To truly understand chronic pain, it's essential to appreciate what pain itself means. Pain is a sensation and the body’s way of signalling damage or potential harm. The definition of chronic pain is a pain that continues for at least three months. Unlike acute pain, which is usually temporary and localised, chronic pain can affect any part of the body and often multiple areas at once. This persistent pain can be a constant companion or come and go, making daily life challenging and sometimes overwhelming.

There isn’t a single cause of chronic pain; it can arise from both, biological and psychological factors. For many people, the debilitating effects of chronic pain significantly diminish their quality of life compared to the general population. Beyond personal suffering, chronic pain has far-reaching social and economic implications, leading to increased absenteeism and reduced productivity. This is particularly concerning given its prevalence: about 34% of adults have reported experiencing chronic pain at some point in their lives.¹

Biological causes

Most types of chronic pain can be characterised as either nociceptive or neuropathic. However, some conditions, such as central pain syndrome (CPS), have mixed biological causes that combine elements of both nociceptive and neuropathic pain.²

Nociceptive pain

The most common type of physical pain is nociceptive pain. It arises from the detection of harmful stimuli by specialised nerve endings called nociceptors. Common examples of nociceptive pain include, but are not limited, to the following:³

• Osteoarthritis 
• Rheumatoid arthritis 
• Chronic Musculoskeletal pain 
• Chronic tendonitis 
• Chronic lower back pain 
• Fibromyalgia 
• Irritable bowel disease 

Neuropathic pain

Neuropathic pain arises from damage or dysfunction in the nervous system and can be felt at different levels, either in the peripheral nervous system or the central nervous system (CNS). The peripheral nervous system includes nerves that extend throughout the body, while the central nervous system comprises the brain and spinal cord. Some examples of neuropathic pain include the following:

• Diabetic neuropathy 
• Post-Herpetic neuralgia 
• Sciatica 
• Carpal Tunnel Syndrome

Central pain syndrome

Central pain syndrome is a unique condition where chronic pain can manifest as either nociceptive or neuropathic pain. It is defined as a neurological condition caused by damage to or dysfunction of the central nervous system (CNS). While this definition sounds similar to neuropathic pain, central pain syndrome differs in that the pain exclusively originates from the CNS. Additionally, central pain syndrome may involve nociceptive pain, as direct injury to the brain or spinal cord can result in pain. This condition can be caused by:⁴ 

• Epilepsy 
• Parkinson’s disease 
• Stroke
• Multiple Sclerosis 
• Tumors 

Psychological causes 

In addition to its biological causes, chronic pain is also associated with various psychological conditions and disorders. While no definitive causation has been established, this is partly due to the diverse range of comorbidities and the complex relationship between chronic pain and psychological conditions. Sometimes chronic pain precedes the psychological condition, while in other cases, the psychological condition comes first.⁵

Anxiety

Anxiety can contribute to chronic pain and is often accompanied by physical symptoms, such as heart palpitations and shortness of breath. Research has shown a significant association between certain anxiety disorders and chronic pain. The prevalence of anxiety disorders among chronic pain sufferers is double that of the general population.⁶

People who suffer from anxiety often have a higher pain sensation. This consequently makes them more susceptible to chronic pain conditions, and studies have shown that people with anxiety disorders report a higher pain perception.⁶

Depression 

Depression, another mood disorder, is the most common psychological comorbidity associated with chronic pain. The relationship between the two forms a positive feedback loop, where each condition exacerbates the other.⁶

Depression can heighten the perception of pain, lower pain thresholds, and diminish an individual's ability to cope with discomfort. Conversely, chronic pain can lead to depression, as persistent pain fosters feelings of helplessness and frustration, contributing to overall depressive symptoms.⁶

Trauma and PTSD

Trauma and Post-Traumatic Stress Disorder (PTSD) are mental health conditions that frequently co-occur with chronic pain, similar to anxiety and depression. While the direct pathways connecting them are not fully understood, there is significant neurobiological overlap. Both PTSD and chronic pain share common neurobiological pathways, and trauma can cause alterations in the brain's structure and function, particularly in areas involved in pain perception and regulation.⁷

Lifestyle and environmental factors 

Environmental factors significantly influence a person’s management and perception of chronic pain. Adopting a holistic, healthier lifestyle generally leads to relief from chronic pain, while an unhealthy lifestyle can exacerbate pain symptoms.⁸

Sedentary lifestyle 

Inactivity and sedentary lifestyles can lead to muscle stiffness, decreased mobility, and reduced strength.⁸ Conditions like osteoarthritis, which causes chronic joint pain, can develop or worsen due to prolonged inactivity or extended periods of sitting. Conversely, increasing physical activity levels can help reduce inflammation and alleviate pain, often without the need for medication.

Poor diet and nutrition

Many foods contribute to chronic pain by being pro-inflammatory, with ultra-processed foods being a prime example. These foods often contain significantly more sugar than natural foods, which can eventually lead to insulin resistance, a major contributor to inflammation.⁹ Additionally, other types of processed foods can negatively impact inflammation as they often contain:  

• Trans and unsaturated fats
• Refined carbohydrates 
• Additives and preservatives 
• Low nutrient density 

Occupational hazards

Some jobs, particularly those in manual labour, are physically demanding and can cause repetitive strain, often leading to injury. These demanding roles involve repetitive movements, poor ergonomics, and prolonged static postures. Over time, this can result in conditions, such as carpal tunnel syndrome and tendonitis, both are associated with chronic pain.¹⁰

Genetic and hereditary factors

Genetic predisposition

Genetic variations can influence pain thresholds, making some individuals more sensitive to pain stimuli than others. Specific variations in DNA, particularly in pro-inflammatory cytokine genes, can result in a lower pain tolerance threshold. This increased sensitivity leaves individuals more susceptible to chronic pain conditions such as fibromyalgia.¹¹ 

Inherited conditions such as Ehlers-Danlos syndrome (EDS) can also predispose people to chronic pain. In the case of EDS, the connective tissue is often weaker and more prone to injury compared with the general population.  The chronic wounds and frequency of the injuries often cause persistent pain.¹² 

Epigenetics

Epigenetic factors have also been linked to a person's perception of pain and pain threshold. Various environmental and lifestyle factors can influence the expression of specific genes.  Changes in gene expression can alter the function, and sensitivity of pain pathways, making individuals more sensitive to pain.¹³ As with many of the causes discussed in this article, these changes can increase the likelihood of experiencing chronic pain.

Medical conditions and comorbidities 

Autoimmune diseases

Autoimmune diseases are characterised by the immune system, mistakenly attacking the body's tissues, leading to tissue damage, inflammation, and chronic pain. Additionally, these conditions often involve dysregulation between nociceptors and immune cells, resulting in heightened excitation of sensory neurons and increased pain perception. Examples of autoimmune disorders that commonly lead to chronic pain include:

• Rheumatoid arthritis
• Systematic Lupus Erythematosus  
• Multiple sclerosis 
• Inflammatory Bowel Disease  

Metabolic disorders 

Metabolic disorders like diabetes frequently lead to chronic pain, primarily through the common complication of diabetic neuropathy. Diabetic neuropathy is characterised by nerve damage resulting from prolonged high blood glucose levels, affecting the peripheral nerves that transmit signals between the brain, spinal cord, and the rest of the body.¹⁴ Additionally, diabetes can trigger inflammatory responses that further damage nerves, contributing to chronic pain.

Infections 

The final cause of chronic pain that we will discuss is infections. Chronic pain resulting from infections can manifest as either nociceptive or neuropathic pain.¹⁵ Various mechanisms contribute to the development of chronic pain in these cases, including the following:¹⁵

• Persistent inflammation 
• Direct tissue damage 
• Nerve injury 
• Autoimmune diseases
• Central sensitization 

Certain infections are more likely to lead to chronic pain. Here are some of the most common infections associated with pain:¹⁵

• Herpes Zoster (Shingles)
• Lyme disease 
• HIV
• Hepatitis C 
• Tuberculosis 

Summary

In summary, chronic pain is a complex condition influenced by various biological, psychological, lifestyle, and environmental factors. It is defined as pain persisting for at least three months and can affect any part of the body, often having a major negative impact on a person’s quality of life.

The main biological causes of chronic pain include nociceptive pain from physical damage, neuropathic pain from nerve dysfunction, and central pain syndrome resulting from CNS issues. Psychological factors such as anxiety, depression, and PTSD work through different mechanisms and can worsen chronic pain through feedback loops, increasing pain perception and emotional distress. Lifestyle choices, like sedentary behaviour and poor diet, also contribute to chronic pain, as do occupational hazards and genetic predispositions. 

Autoimmune diseases, metabolic disorders like diabetes, and infections are medical conditions that frequently lead to chronic pain through mechanisms such as persistent inflammation, tissue damage, and nerve injury. Common infections associated with chronic pain include herpes zoster, Lyme disease, HIV, hepatitis C, and tuberculosis. Understanding these diverse causes is essential for the effective management of chronic pain.