PI Brief Update

Understanding the Mechanisms of Chronic Pain - Dr Mark Burgin

20/06/23. Dr Mark Burgin explains why advances in the assessment of chronic pain has led to a change in understanding with treatments increasingly directed at components of the pain.

Chronic pain is pain that lasts for more than 12 weeks and can have a significant disabling impact on a person's life. It can interfere with sleep, work, relationships, and leisure activities. It can also lead to depression, anxiety, and social isolation.

Chronic pain is a complex condition that can be caused by a variety of factors, including injury, disease, and emotional distress. The exact mechanisms of chronic pain are not fully understood, but for several decades the leading theory has been a change in the way the nervous system processes pain signals.

In the normal state, pain signals are transmitted from the affected area to the brain through a series of nerves. When tissue is damaged, nociceptors (specialised nerve cells) send pain signals to the brain. These signals are processed by the brain, which interprets them as pain.

In chronic pain, the nociceptors become sensitised, meaning they become more easily activated. This can happen due to a variety of factors, including inflammation, injury, and disease. When the nociceptors are sensitised, they send pain signals to the brain even when there is no tissue damage.

There are several problems with this theory, first finding a drug to desensitise the nociceptors has been unsuccessful, second there are other factors that appear to be at least as important and third it does not explain the association with chronic fatigue.

Evolving understanding

It is now recognised that another key mechanism of chronic pain is central sensitisation. This is a process that occurs in the spinal cord and brain. When nociceptors send pain signals to the spinal cord, they can activate a network of neurons that become more sensitive to pain signals. This can lead to a vicious cycle, where the brain becomes more and more sensitive to pain so that normal sensations are interpreted as pain.

Treatments have been developed to modify this mechanism such as antidepressants and anti-epileptic medications. This had led to increasing research interest in the central sensitisation mechanism, but the exact cause is still unclear.

Psychological factors. The ability to cope with pain is variable both between people and within the same person. Pain can become a focus for anger and chronic anger and chronic pain can become entangled. Anger can be a common reaction to chronic pain in the absence of mental illness. Anger can increase feelings of frustration, irritability, and fatigue and cause vicious cycle.

Although treatments such as antidepressants could work on psychological factors the doses used in chronic pain are lower than those used for depression. Similarly counselling appears to have a minor effect on the coping strategies but is largely ineffective at improving chronic pain. Where psychological help is useful is in managing the psychological pain from the adjustment of being disabled.

Loss of conditioning. There is strong evidence both for rest as a cause of chronic pain and exercise as a treatment for the pain. The problem has been that most sufferers of chronic pain are strongly avoidant of exercise. The patients state that any exercise causes a flare in pain although studies show that continuing exercise for weeks does improve function.

It is likely that both sides are correct, an increase in pain after exercise is almost universal and there is a significant risk of injury for a person in pain trying to exercise. This will be worsened in those with chronic pain and make it difficult or impossible to continue safely. Equally it is likely that exercising regularly does reduce the central sensitisation and reduces the risk of chronic pain arising in the first place. There is an urgent need for more rehabilitation facilities such as hydrotherapy where the sufferer can exercise safely.

Vitamin D and pain. Although Vitamin D deficiency is recognised as a cause of MSK conditions such as osteomalacia in adults there is little evidence that treatment prevents or treats chronic pain. As it is safe and cheap it is reasonable to recommend Vitamin D supplements for those with pain. There is some evidence that Vitamin D can improve response to other treatments.

Recent interest in genetic variability in pain has led to the discovery of people without normal pain sensation. There are likely to be many genes which make a person more susceptible to chronic pain. These genes may help doctors recognise those with risk factors for chronic pain but are not likely to translate to practical therapies. A genetic test for risk of chronic pain might be available in the near future.

Chronic fatigue

Chronic fatigue may help scientists understand chronic pain. Although it was thought that chronic fatigue was a separate condition there is increasing evidence that they share mechanisms. Theories for the association of fatigue with chronic pain have included:

• Decreased physical activity: People with chronic pain often have difficulty exercising, which can lead to decreased muscle mass and strength. This can make it more difficult to perform everyday activities, which can further contribute to both fatigue and pain.

• Sleep disturbances: Many people with chronic pain also experience sleep disturbances, such as insomnia or restless leg syndrome. This can lead to fatigue during the day and decrease ability to cope with pain.

• Depression and Anxiety: These are common co-conditions of chronic pain. They can cause fatigue, as well as other symptoms such as low mood, loss of interest in activities, changes in appetite, muscle tension, restlessness, and difficulty concentrating. These other symptoms can decrease ability to cope with pain and increase sensitivity to pain.

Whilst these theories explain some features of chronic fatigue they have largely been discounted by those suffering from the problem. This has been accepted by national guidelines which no longer recommend antidepressants and graded exercise as these are ineffective. The guidelines now recommend pacing (keeping active within the person’s limits)

Recent work on the pain and fatigue associated with Long Covid has suggested another mechanism that could connect the two. Fatigue appears to be a neurological problem, the pattern of impairments including orthostatic tachycardia indicates that in Long Covid the brain has been injured. Neurological injury would also explain central sensitisation and any treatment for this problem is likely to cause improvement to both fatigue and pain.

Further research

MSK factors. Pain and changes on x-ray are poorly correlated. Although osteoarthritis can be painful many of those with advanced OA do not suffer from significant pain. When they develop pain the scanning confirms that there is OA but does not explain why it has suddenly become painful. It has been suggested that issues such as nerve irritation may be important. The theory is that when a nerve is injured it swells making it more likely to be injured again.

This theory predicts that if the nerve that is irritated can be identified and prevented from suffering further injury that it will recover. Physical treatments such as soft tissue massage, mobilisations and newer electrotherapy could be used more precisely to help those with chronic pain. Although nerve irritation can be detected clinically by symptoms and tenderness with pressure over the nerve there are no reliable tests available to detect nerve irritation.

Nerve conduction tests are difficult to perform and cannot distinguish between the pain and other pathways. Ultrasound of nerves can detect gross changes in the nerve but cannot identify minor changes. MRI is good at detecting the cause of nerve entrapments in the spine but is less good at detecting impinging nerves. At present detecting this issue depends on the clinical skills of the practitioner and appears to explain much of the interprofessional differences in outcomes.

Conclusions

Multifactorial pain. It is clear that most if not all chronic pain sufferers have more than one cause of their pain. This means that a single treatment cannot resolve the pain but also that many people with chronic pain have treatable causes. Anaesthetic specialists and a multidisciplinary team run pain clinics but rely upon the referring specialist or GP to fully investigate the patient before referral.

The use of medications to treat chronic pain has fallen out of favour partly because they are largely ineffective at improving the condition and partly because of the dangers associated with their use especially risk of addiction. The relative effectiveness and safety of exercise therapy, psychological support and physical treatments has led to these being recommended first line.

There is increasing interest in identifying and freeing up individual nerves which are irritated, understanding the basic mechanisms behind chronic fatigue and the prevention of chronic pain using lifestyle changes. As those with high risk of chronic pain are recognised these approaches can be targeted at those with greatest need.

For those suffering from chronic pain the prognosis may currently be poor and the treatment can feel one-size-fits-all. A holistic assessment can often detect treatable causes of pain which can reduce the pain burden even in those with a long history of pain. Seeing pain as multiple conditions means that most sufferers of chronic pain can achieve at least partial relief. In the future integrated understanding of pain and fatigue may lead to a major breakthrough in pain management.

This article was written with assistance from the Bard Large Language model from Google.

Doctor Mark Burgin, BM BCh (oxon) MRCGP is on the General Practitioner Specialist Register.

Dr. Burgin can be contacted on This email address is being protected from spambots. You need JavaScript enabled to view it. and 0845 331 3304 website drmarkburgin.co.uk

Image ©iStockphoto.com/ChesiireCat

This is part of a series of articles by Dr. Mark Burgin. The opinions expressed in this article are the author's own, not those of Law Brief Publishing Ltd, and are not necessarily commensurate with general legal or medico-legal expert consensus of opinion and/or literature. Any medical content is not exhaustive but at a level for the non-medical reader to understand.