There has been much discussion over the years about why some patients develop symptoms of chronic pain in the absence of any clear ongoing pathology. Patients generally assume that a feeling of pain in a particular location must indicate pathology in the same location and can find it understandably difficult to accept that there is no finding of any pathology. Clinicians have often tried to explain the symptoms as ‘damaged nerves’ and this is a common assumption even though in many cases no nerve damage can be identified. It is also not always clear why there should be nerve damage.
There are conditions where local damage to nociceptors can lead to their sensitization, and there can be alterations in central nociceptive pathways with changes in neuronal populations. Damage to nerve fibres can continue for prolonged periods with associated neuropathic pain, however this is associated with measurable factors such as raised inflammatory markers such as cytokines, or general markers such as CRP and ESR. Sensitisation of nociceptors can be associated with ‘allodynia’ where local light stimulus can cause an exaggerated pain response. These changes are expected to settle once the cause of the ongoing nerve damage resolves (for example when inflammation from a recently damaged intervertebral disc settles).
Much work has been done to elucidate pain pathways and this itself can be very helpful in explaining why some people may experience more pain than others. Besides having specific nociceptive (pain) nerve fibres which take signals to the spinal cord, there are feedback processes at spinal cord level where both negative and positive interactions take place between nerves from other peripheral locations and descending fibres from the central nervous system. These inhibitory and excitatory mechanisms are normally in balance, but selective damage to some nerve fibres may alter this balance to increase the excitatory function.
The action of various drugs can also indicate the location of any apparent problem. Drugs acting to suppress inflammation (particularly anti-inflammatory drugs) will clearly help where there is local inflammation. Opiate analgesics don’t work at local level but have effects at the spinal cord, similar to the inhibitory effect of other nerves at this level. This is not surprising as that is where opiate receptors are found. There are also central opiate receptors within the brain that have similar effects. Inhibitory pathways can also be enhanced by the central effects of serotonin and noradrenaline re-uptake inhibitors, in particular the tri-cyclic anti-depressants, hence their dual action in helping with both pain and depressive disorders.
Much recent research has considered central processing of pain. After all, pain is only experienced if it is processed centrally. Two major advances in understanding how pain is processed centrally, and how this may differ in chronic pain patients, has come from fMRI studies. When normal subjects are compared to subjects with chronic pain, there appears to be no difference in the level of processing of pain centrally; there does not appear to be a greater stimulus reaching the brain. What does appear to be happening is the development of greater ‘saliency’ in chronic pain patients (Mouraux et al., 2011, Legrain et al., 2011). They have a greater propensity to perceive pain at a given stimulus. In essence this could be considered to be the ‘pain threshold’ where patients with chronic pain have a lower threshold for perceiving a stimulus as painful. In amputees, there is also good evidence from fMRI that there is some re-organisation of the primary sensory cortex, with activity levels that simply should not be present if the limb is missing, as there should be no sensory input. The re-organising that has taken place appears to cause intrinsic sensations of pain that are not dependent on external input. More importantly, therapies developed as a result have shown that this cortical re-organisation is reversible (Flor et al., 2001, Flor, 2003).
Changes in cortical saliency can be treated with drugs which suppress brain activity. The group normally used in this way is the anti-epileptic drugs and two particular ones have proven efficacy in chronic pain management, Gabapentin and Pregabalin.
Overall these studies suggest that chronic pain may develop as a consequence of prolonged local nerve damage, an altered balance between excitation and inhibition and a process of cortical re-organisation. Local damage should improve as local factors, particularly inflammation, settle. Cortical re-organisation has been shown to be at least partially reversible. Where there is a clear neuropathic element to pain, treatment should therefore be a combination of appropriately acting drugs alongside therapy to reverse any cortical re-organisation that has led to increased saliency.
The fact that cortical re-organisation appears to happen separately to any specific pain pathway pathology suggests that thought processes influence the development of chronic pain. Observations of patients with chronic pain compared to normal subjects have shown consistent differences in a number of psychological variables. Key factors include helplessness, lack of coping skills and catastrophising. Pain catastrophising in particular is associated with disability and enhanced pain behaviours and is also associated with hypervigilance. Patients who catastrophise are shown to have significantly higher cortical activation of the somatosensory cortex, anterior cingulate cortex and lentiform nuclei. This strongly suggests that catastrophising is associated with development and persistence of chronic pain, and is a modifiable behavior rather than a fixed neuronal problem. Modification is generally achieved through simple cognitive behavioural therapy.
Studies have shown that there does not appear to be an increase in pain stimulus in patients experiencing chronic pain; the problem is their enhanced perception, or the ‘lowering of their pain threshold’. Treatments aimed at reducing painful input will inevitably therefore fail, as this is not the problem. Having the goal of ‘curing’ chronic pain is not only inappropriate, but in practice it is rarely achieved. The aim should be to change the perception of pain so it is no longer so troublesome, and the patient is able to cope with normal activity.
A study looked at long term outcomes in fibromyalgia in patients severe enough to require specialist care from a rheumatologist rather than primary care only. This demonstrated that only ten percent of 1555 patient has a substantial improvement in pain and 15% had a moderate improvement in pain. Some patients take this as proof that their condition is ‘permanent’ and ‘will not get better’. However the same study looking at long-term functionality found that at baseline only 29.1-34.5% were work-disabled in spite of very high levels of distress, during the study there was significant fluctuation of symptom levels to the extent that 44% failed to meet the criteria for a diagnosis of fibromyalgia at some point during the eleven years, overall there was improvement, to the point where around 75% of patients were able to function without disability at work (Walitt et al., 2011).
When considering outcomes in a condition that is essentially subjective and results from behavior and belief rather than an identified pathology, care should be taken when stating that recovery is not expected. It is not expected if the patient has poor insight, or does not engage fully with treatment. It is also very unlikely to change if the patient focuses mostly on entitlement to the sickness role and health anxiety. If the patient sees a reduction in entitlement or an increase in expectation as a result of recovery, this is likely to have a negative impact on their motivation to recover and their confidence that they can cope if they do recover. Having symptoms can then become the primary coping strategy for them in life. It becomes increasingly important that they maintain a level of disability that ensures they do not have to cope, and this in turn is likely to lead to the apparent exaggeration in symptoms often seen in chronic pain or chronic fatigue patients.