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MODERN CONCEPTS OF PAIN

 

INTRODUCTION

The assessment, investigation and management of pain is perhaps the most important function of any doctor, whichever speciality they find themselves.

We all will suffer pain at some time in our lives.  Many of us will have pain every day.  From an evolution perspective, pain and the ability to get early warning by unpleasant stimulation of the body is protective.

We have nerve fibres that literally go to every millimetre of our body and will generate neural impulses that will be perceived by the brain as pain under the appropriate circumstances.  The one exception to this is the actual brain itself which does not have its own nerve supply.

Useful pain is best demonstrated by local injury or in the prevention of damage if, for instance, a hand is placed on a hot stove.

Our response is instant and the finger or hand is removed very promptly, hopefully before more severe damage takes place.  This is a reflex withdrawal response and is fundamental to our long term survival.

Pain may arise from internal organs.  Anyone who has suffered with renal colic or gallstone colic will know how severe this can be.  All of these pains can be regarded as “useful” pain.  They warn of either impending danger or that something is going wrong with our bodily systems.

Pain can only be appreciated by the brain.  All the nerve fibres generating pain impulses effectively end up in various structures of the brain that in turn feed pain awareness into our all knowing and thinking frontal lobes that control behaviour.

Unfortunately, under a number of circumstances, pain will emerge and often continue that does not seem to have a useful purpose.  In my clinical practice I have tended to call this “useless” pain.  It certainly does not help us in our day to day living experience and for many will have a significant negative impact on the quality of living experience.

Chronic daily headache, including chronic migraine, and even acute attacks of migraine can be thought of as “useless” pain.  People who have the fibromyalgia syndrome, chronic neck or back pain and many other examples of pain associated with depression and anxiety, do not seem to gain significant advantage in living by virtue of the pain that is suffered on a regular basis.

The perhaps all to obvious association of chronic pain with a low mood and depression, as opposed to acute pain that is usually associated with anxiety, has led doctors over the years to think that chronic pain is a psychological disorder.  This same thinking interestingly has pervaded and perhaps blocked intellectual discussion about what I regard as a near related disorder, namely the chronic fatigue syndrome that used to be wrongly called ME.

It is remarkable to think that our understanding of pain, given how often it presents in clinical practice, has only really developed to any significant extent over the last 10 years or so.  Some current thoughts about pain, how it is generated and how then it can best be treated, are discussed below.

 

THE APPRECIATION OF PAIN

Pain involves what is called a nociceptive stimulus.  This activates neural structures which send signals into the central nervous system.  What then follows is the perception of pain by the individual.  By virtue of recognising that there is pain, the individual then experiences suffering.

It is the suffering that then in turn results in varying degrees of pain behaviour.  That pain behaviour may take many forms, depending on the genetic make up of the individual and their earlier experiences in life.

For instance, where a sufferer has perhaps been exposed to a great deal of anxiety about health in childhood or as a consequence of having very anxious family, particularly parents, then pain behaviour may be quite complex and become more difficult to put in perspective.  What may be a very severe pain to one person with regard to behaviour might in another individual be much less significant.  We do not, however, have any simple comparator measure.

Occasionally, in clinical practice, situations arise that allow for such comparisons of different pains to be made.

Recently, I saw one of my patients who is a migraine sufferer.  They had always been quite genuine about their migraine attacks and the major impact that they were having on their life.

When they missed an appointment ,which was so unlike them, I did ask at the next visit if anything had been wrong and they explained that they had suffered a bout of renal colic.  Renal colic involves the formation of a stone in the kidney which then moves down the ureter towards the bladder before hopefully being passed in the urine.  It is recognised as being amongst the most painful conditions that can afflict mankind.

When asking my patient if they would care to make a comparison between the pain of renal colic and their migraine, which they had always found so incapacitating, they responded that they would never complain about migraine again.

 

THE IMPACT OF PAIN

Pain affects all aspects of the living process.

Pain specialists talk about the quality of life (QoL).

With regard to the functional status of the individual, it is necessary to consider the physical functioning, the ability to perform activities of normal living and then whether or not work is affected and then recreation and leisure activity.

At the same time the psychological state of any person with pain will need to be considered.  This is known as the psychological morbidity and often includes depression, anxiety, anger, sleep disruption and loss of self esteem.  In some circumstances, it may be necessary to consider if there is a so-called post-traumatic stress disorder.

Chronic pain impacts on the social condition.  Chronic pain often leads to marital and/or family conflict.  Intimacy and sexual activity will be diminished and social isolation generally may occur.

Chronic pain also has socio-economic consequences with the cost of healthcare, the cost to society of individuals being regarded as disabled or possibly being retired sick and then just the lost efficiency when at work or the complete loss of time through sick leave.

What should be apparent both from a medical and lay perspective, is that chronic pain impacts greatly and needs to be treated.

 

HOW CAN PAIN BE TREATED?

My article under headache management discusses this concept and, with the assumption that there is no surgical treatment, then it is usually recommended that a multi-disciplinary approach using a range of treatment strategies needs to be put in place.  These include the following:-

  • Pharmacotherapy

  • Interventional treatment, such as injections

  • Psychological support

  • Lifestyle change

  • Intergrative therapy

  • Physical rehabilitation

The difficulty in the United Kingdom is to try and get this range of treatment concurrently and consistently, particularly when there are so few pain clinics for the number of patients that need them and few physical therapists who specialise in pain management and who in any case have sufficient time to offer enough sessions.

 

THE CURRENT ”PAINKILLERS” AVAILABLE

In terms of drug therapy, we have three simple groups of mild to moderate analgesia.  These include aspirin, paracetamol and non-steroidal anti-inflammatory drugs of varying strength.

More potent pain relief is provided by the opiates, starting with codeine, moving through tramadol and buprenorphine and ending with morphine and diamorphine variants.

There are far fewer analgesic preparations available than most lay people realise.  When it is then recognised that a number of patients cannot take aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) because of gastric side effects, this limits the choice even more.

Many patients also find themselves sensitive to opiates because of their particular side effects.  Pain relief under these circumstances can be particularly challenging.

A number of other medications have been determined to have pain relieving properties.  Drugs in the anti-epileptic group and also medicines that are primarily used as antidepressants are known to cause descending modulation between the brain and the spinal cord and hence reduce the pain input to the central nervous system.

Central sensitisation can be reduced by the same group of drugs, including opioids. 

There are also a number of treatments, such as local anaesthetics, topical analgesics, capsaicin and the previously mentioned three groups of drugs that seem to reduce peripheral sensitisation, that is blocking the peripheral nerve input into the spinal cord.  The fact that the anti-epilepsy drugs and the antidepressants seem to work at all three levels is the reason why these medications can be particularly helpful in blocking pain pathways.  The key is to find the regime that works for each individual.

 

THE STEPWISE APPROACH TO PAIN MANAGEMENT

When any individual presents to a General Practitioner with pain they will tend to receive paracetamol, aspirin or NSAIDs.  General Practitioners are beginning to use neuropathic pain blocking drugs (usually anti-epileptic agents) and antidepressants within first line pain management.

When the pain is not controlled then opiates tend to be added with more powerful NSAIDs and whatever adjuvant type therapy has not been used to date.

It is only when pain is found to be refractory, that is not responding to all the baseline treatments, that a range of other management techniques, usually provided by a pain specialist, are considered.  These include spinal and epidural blocks, selective nerve blocks, neurostimulation or ablation, iv lignocaine injection, a trial of ketamine and a range of other somewhat esoteric pain blocking procedures, including surgical intervention.

 

CENTRAL SENSITISATION AND SYNDROMES THOUGHT TO BE CAUSED BY CNS DYSREGULATION

There are a range of conditions that bring fear in the minds of many clinicians who do not see people with chronic pain on a regular basis.  These include:-

  • Fibromyalgia

  • Complex regional pain syndrome

  • Temporomandibular joint dysfunction

  • Irritable bowel syndrome

  • Interstitial cystitis

  • Chronic prostatitis

  • Pelvic pain syndrome, including testicular pain syndrome

  • Chronic fatigue

  • Tension headache

Each of these conditions has had quite a significant bad press mainly due to the lack of understanding about the nature of the disorder and also the complex personalities of people who seem to either get these conditions or find that their psychological state is changed and challenged by virtue of the condition.

Each of these conditions is characterised by severe persistent pain.  This seems to be disproportionate to any disease process or tissue injury that may or not be apparent.  There is always emotional distress.  Behavioural dysfunction is inevitable both at work, home and recreation.  Fatigue with sleep disturbance is universal and there will be diminished libido, complaints of memory and concentration difficulty, as well as a feeling of generalised stress (not being in control) and a tendency towards hyperarousal to many different environmental stimuli.

 

FIBROMYALGIA

It would be reasonable to say that many doctors do not perceive that there is a condition called fibromyalgia.  My perspective on this disorder is that I see a number of people in my clinical practice and I know that colleagues have similar experiences with case series published in the literature, all of whom have a similar presentation.

This involves a syndrome of widespread bodily pain above and below the diaphragm.

It would seem that fibromyalgia patients have a heightened sensitivity to pain.  Likewise, relative non-noxious stimuli may result in pain for those individuals, whereas it would not in the normal population.

What really confuses is the fact that this group of people will also have a wide range of additional symptoms, including muscle tenderness, sleep disturbance and fatigue.

Fibromyalgia is common and may affect between 1 and 5% of the whole population.  The majority of people are between 35 and 60 years of age and there is a greater tendency for women to be affected.

Over the years, the condition of fibromyalgia has been denied as a true disorder.  It has been thought about as a problem involving muscles, tendons or soft tissue.  It has been loosely referred to as a psychosomatic condition or that it only occurred in somewhat histrionic middle class women.

None of these thoughts have stood the test of time and it is much more likely to represent a disorder of brain modulation.

We know, for instance, now that there are a number of neurotransmitter substances and chemicals within the brain that facilitate, that is excite, pain pathways.  These chemicals include substance P, glutamate, nerve growth factor and CCK.

A number of inhibitory pain pathways are known, including descending inhibitory pathways onto the thalamus, serotonin and dopamine pathways, opioids occurring naturally in the nervous system, as well as the compound GABA, adenosine and even cannabinoids.

It would be a reasonable hypothesis to suggest that the genetic make up of different people makes certain individuals more likely to develop problems with chronic pain as the same consideration would make it more likely that an individual might develop depression, personality disorder or even epilepsy.

 

INCREASED CENTRAL SENSITIVITY

We know that under certain circumstances the brain becomes more responsive to stimuli.  Injury will produce hyperalgesia which is a heightened sense of pain to a painful stimulus or allodynia, which is a sensation of pain generated by what would not be regarded as a painful stimulus.

It is known that injury can create both of these pain phenomena.

 

WHERE IN THE BRAIN DO THE PAIN PATHWAYS ORIGINATE?

It used to be thought that the thalamus, that is a structure situated deep inside the brain was primarily responsible for pain.

Special imaging techniques now show us that this is not correct and that a number of structures, including the so-called prefrontal cortex , anterior cingulate cortex, somatosensory cortex, insular cortex and the amygdala are all important in the way that pain is perceived.

In simple terms what this means is that pain comes from the brain.

If there is a nociceptive symptom anywhere in the body, it is the brain that will perceive that fact.

The four important issues of pain production are as follows:-

  • Individual differences
    a.      Genetic
    b.      Gender
    c.      History of injury
    d.      Atrophy

  • Mood
    a.      Depression
    b.      Anxiety
    c.      Catastrophising
    d.      Emotional context

  • Cognition
    a.      Attention
    b.      Distraction
    c.      Hypervigilance
    d.      Catastrophising
    e.      Re-appraisal
    f.       Hypnotic suggestion

  • Context
    a.      Belief
    b.      Expectation
    c.      Placebo
    d.      Motivation
    e.      Nocebo effect

 

DO THE EXPERIMENTAL STUDIES SUPPORT THE IDEA OF BRAIN AND PAIN?

The simple answer to this question is yes.  Where trials have been carried out, elevated amounts of glutamate and substance P have been found in those with the syndromes, compared to normal controls.  Magnetic resonance spectroscopy has demonstrated, for instance, higher levels of glutamate in a part of the brain called the right posterior insular.

A study looking at the effect of exercise on individuals with fibromyalgia showed that in normal people exercise reduced pain but the opposite effect was seen in those with fibromyalgia.

Other studies showed that people with fibromyalgia were more sensitive to the effect of hot and cold in generating pain than the normal population.

Similarly, studies looking at inhibitory pain mechanisms demonstrated that people with fibromyalgia lost inhibitory control.  The nature of these clever experiments is outside the brief of this simple article but again the science seems to hold true.

It has also been shown that in fibromyalgia there was impaired pain inhibition.

What is perhaps more worrying is that in a study comparing fibromyalgia patients to healthy controls there was found to be a loss of cerebral grey matter greater in the fibromyalgia sufferers compared to the normal population.  The study, however, was challenged when it was found that if anxiety was taken into account, then fibromyalgia had no effect on brain thinning.

Strangely, in other conditions, such as temporomandibular joint dysfunction (TMJ pain), this showed similar findings to those in fibromyalgia.

 

COMPLEX REGIONAL PAIN SYNDROME (CRPS)

With this background information, it is not surprising that central nervous system changes are seen in people with CRPS.  It appears from various studies that there is cortical reorganisation in people who have CRPS.  It would appear that the presence of injury and enduring pain will then have a negative feedback on the brain structure itself.  This in turn leads to a greater likelihood of pain.  This is actually the reason why anyone who has injury with pain must be encouraged to use their limb as much as possible.

Once again, a number of studies have shown specific changes on functional MR studies in individuals who have CRPS.

 

PAIN, THE BRAIN AND LOVE

American pain specialists discuss the brain in terms, not just of pain but also how there is a Brain Reward and analgesic system built into itself.

They quote Sophocles (496BC-406BC) “One word frees us of all the weight and pain of life.  That word is love”.

It is commonly experienced that when we are with the person that we love we “feel great”.  When we are not with that person, there will be obsessive thoughts of the person and a feeling that we cannot wait until we see them again.

The psychological characteristics of early, intense romantic love would be:-

  • Euphoria

  • Extra energy

  • Intense focused attention

  • Obsessive thinking

  • Emotional dependency

  • Craving

Once more a whole range of areas within the brain are responsible for these feelings and can be seen to literally light up with appropriate functional MRI scanning.

Individuals who find themselves deeply in love are likely to have less pain responsiveness than the reverse.  That is not true for all situations, but it certainly reflects on the sense of wellbeing.

 

THE MANAGEMENT OF PAIN

Pain management is best multimodal.

Assuming that there is no surgical option, then there are effectively four styles of treatment as follows:-

  • Physical as administered by a physiotherapist, osteopath or chiropractitioner

  • Injection as represented by acupuncture, TENS machines and local injections into painful areas

  • Talking therapies.  This involves the psychological and psychiatric management of chronic pain.  Different people respond in different ways to psychological counselling and appropriate psychiatric treatment.

  • Pharmacotherapy.  This means anything that is drug orientated or represents what is placed in the mouth.

There are some stimulation techniques that are also used which would include a TENS machine, deep brain stimulation and epidural stimulation.

 

PHARMACOLOGICAL TREATMENT

The various pharmacological treatments include the following:-

  • Topical analgesics, such as capsaicin or the lidocaine patch 5%.

  • Anti-epilepsy drugs, such as gabapentin, pregabalin, lamotrigine, valproate, carbamazepine and levetiracetam.

  • Antidepressants and this would usually mean the tricyclic antidepressant drugs, but other medicines, such as duloxetine, mirtazapine and citalopram can be considered.

  • Opioids, such as oxycodone, oxycontin and tramadol.

  • In headache management vitamin B12, compound Q10, magnesium and butterbur can be tried.

 

TALKING THERAPIES

Many people with chronic pain find it difficult to understand that talking therapies have a fundamental role in treatment.  All sufferers with chronic pain have a lowness of mood at least and many depression.  Pain causes depression and depression may lead to pain.  Psychiatric opinion and cognitive behavioural therapy will unravel background difficulties and focus on ways to cope better with the pain.  Frank depression may need its own specific treatment.

A full discussion on talking therapies is beyond the scope of this article but a take home message is this.  If you have chronic pain, you may well get significant help by referral to a consultant psychiatrist with an interest in pain management, together with a clinical psychologist.

 

PHYSICAL THERAPIES

Physical treatments are given by physiotherapists, osteopaths and chiropractitioners, to name a few.  These individuals focus on keeping limbs and the axial skeleton mobile and active as well as introducing a range of distracting treatments.  Each therapist has their own style and offer support and encouragement as part of the treatment process.

 

INJECTION TREATMENTS

Injection treatments include acupuncture (and acupressure), transcutaneous electrical nerve stimulation (TENS) and various actual injection techniques that tend on the whole to inject a low dose of steroid with or without local anaesthetic into various structures which may be contributing to the cause of the pain.  Sometimes such treatments seem to distract the brain, as seems to be the case with TENS, or it may generate the release of pain relieving chemicals, as can occur in acupuncture.

 

CONCLUSIONS

Our understanding of pain and, in particular, chronic pain, is evolving rapidly.  Modern imaging teaches us that many preconceived ideas about people who suffer pain have been incorrect.

On the whole people who have pain, just have pain, and it is likely to be a genetic vulnerability that plays a fundamental role.

If you are unlucky enough to suffer with chronic pain, then it is necessary to find the regime of treatment that works for you.  It is always best to keep an open mind so that every treatment can be tried. If you have preconceived ideas, then you will effectively end up treating the pain yourself and effective therapies are likely to be missed.  The biggest difficulty with the NHS, as I see it, is the problem in getting access to the resources that are usually required by those who have any kind of pain disorder.