Chronic Pain Management
DR JCD Wells M.B., Ch.B., F.R.C.A
The physician faced with a patient in chronic pain has several important tasks. The first is obviously the assessment of the pain and its various causes, including physical and psychological components. Realising that pain is a bio-psycho-social phenomenon, all of these aspects have to be addressed in the history and evaluation of the patient. Only when a proper evaluation has been made can appropriate treatment be carried out. Only the most naive of clinicians would take a simplistic mechanistic approach, or indeed go the other way and dismiss pain as "all in the mind".
Such assessment is complex and beyond the scope of this short presentation. However, I make it clear that this has to be undertaken, and undertaken well. Not only does the pain have to be evaluated, but so does the distress that it causes the sufferer and whether this feeds back to have a major part of the pain itself. Finally disability has to be considered; is it appropriate for the known nociceptive disease, or inappropriate? Is the disability that has developed a major factor in the chronicity?
Once this assessment has been made, management can be developed along appropriate lines. The distress should be minimised and disability should be reduced. Sometimes this can be done with great effect (eg, through Pain Management Programmes) without altering the actual amount of pain. On the other hand, sometimes relief of the pain (for instance appropriate intervention) will alleviate distress and reverse the disability.
In most cases it is impossible to completely alleviate pain and thus a management plan has to be agreed with the patient. This may involve a rehabilitation approach, including increased mobility, perhaps in conjunction with a physiotherapy team, or the patient's own exercise programme. These will be facilitated by appropriate analgesic techniques. These various techniques will now be considered.
The different types of strategies that can be applied are as follows:-
Most interventions that any Pain Clinic offers fall into one of these categories.
i) Non-steroidal anti-inflammatory drugs (NSAIDs) have been used for 150 years in Europe, and probably for a great deal longer in the East, in the form of willow bark extract. Useful when given appropriately, examination of the chronic pain population indicates that a very high number of patients are intolerant to these drugs because of gastrointestinal or other side-effects. There are two possible hypotheses for this. Firstly, chronic pain sufferers tend to be somewhat hypochondriacal and intolerant of body symptoms in general and thus less tolerant of real or perceived side-effects when taking medication. The second is that there may be a sub-group of patients whose pain is not managed well early on. NSAIDs may produce side-effects, limiting their use. With no pain relief, the patient fails to exercise. This hampering of their rehabilitation because of inadequate analgesia may contribute significantly towards the chronicity.
Recently COX2 antagonists have come on the scene, but the first wave of these have been disappointing in the UK, in that the side-effect profile does not appear to be particularly better than the present drugs (Meloxicam, Etodolac). The newer drugs, Vioxx and Celebrex, are now available in the USA and will soon become available in Europe. Their arrival is awaited with eager anticipation, but the results may prove to be disappointing. The products may not be as side-effect free as they first seem.
ii) The use of opioid drugs for the management of chronic non-malignant pain is fraught with difficulties, some real and some perceived. Morphine itself has tended not to be prescribed for chronic pain, because of a fear or stigma concerning Morphine. Physicians may fear dependence, tolerance and side-effects. There is a wide difference of opinion, which is still to be resolved; however, some patients can have their pain adequately controlled with opioids, without an unacceptable level of addiction problems. The potential risk of addiction remains a very real problem for a minority. Also, a significant number of patients with chronic pain complain of bothersome side-effects from medication. Mobility and distress must be monitored and benefits must accrue in both these parameters, as well as in reduction of pain.
iii) In the UK and in the USA, traditionally most patients with chronic pain receive an opioid derivative such as Codeine, Dihydrocodeine or Dextropropoxyphene. In the past Pentazocine and Buprenorphine enjoyed a passing vogue but are now little used. Pentazocine proved to have unacceptable side-effects, and Buprenorphine, originally thought to be non-addictive, was shown to have addictive potential and since being classified as a controlled drug has enjoyed little popularity. Nefopam has limited efficacy and popularity, and Meptazinol is short-acting, and often associated with an unacceptable level of side-effects.
Recent work suggests that Codeine and Dihydrocodeine are merely pro drugs for Morphine, and exert their action through metabolism to this compound. Given that a significant number of the population do not have the metabolic pathway to facilitate this, it is not surprising that there is a significant failure rate to produce any analgesia at all and that patients getting analgesia seem to get limited relief-hence possibly the popularity of these preparations being compounded with Paracetamol. There is good evidence that in some patients, much of the analgesic effect in these combined preparations lies with the Paracetamol itself, whilst many of the side-effects lie with the opioid.
v) Tramadol hydrochloride is an orally active, clinically effective, centrally-acting analgesic. It can produce analgesia that has been compared to Codeine or Dextropropoxyphene. It has been used in post-surgical pain, obstetric pain, cancer pain and chronic pain of mechanical and neurogenic origin. Analgesic tolerance is not a significant problem, and psychological dependence and euphoric effects are minimal. There are a significant number of patients in the chronic group who develop side-effects, but many of those who tolerate the drug get useful benefit in pain reduction. This slow-release formulation is an appropriate vehicle for chronic pain management.
Tramadol has an affinity, albeit relatively weak, for mu opioid receptors. It is also a neuronal uptake inhibitor. The monoamine neurotransmitters 5HT (Serotonin) and Noradrenaline (NA) are involved in the inhibition of spinal cord dorsal horn neurone responses to painful stimulation (i.e. closing the gate). Analgesia can result from activating the pain inhibitory pathways originating from higher CNS levels, and containing these neurotransmitters. Tramadol inhibits the uptake of 5HT and Noradrenaline but not Adenosine, Cyclic AMP, Dopamine, or Gaba.
Metanalysis by Moore and McQuay indicates an appropriate dose response curve for Tramadol, and suggests a reduced number needed to treat to show therapeutic efficacy as compared with Codeine, in doses of 75 to 150 mg. Nausea, vomiting and dizziness are greater than with Codeine, somnolence about the same and constipation much less. In the chronic pain situation nausea and vomiting are attenuated with usage, as is somnolence for both drugs, but constipation remains a particular problem with Codeine and Dihydrocodeine, and less of a problem with Tramadol.
Side-effects from Tramadol can be minimised by starting with a low dose and increasing gradually. There is evidence that this reduces the side-effects and improves tolerance. According to need, it can be started in a low dose of 50 mg daily or twice a day, and gradually titrated to reach 50 mg three times a day by day 3. Once a patient is established on a therapeutic dose, they can be put on the slow-release formulation to provide round-the-clock analgesia.
B. PSYCHOACTIVE DRUGS.
i) Anticonvulsants are well acknowledged as being effective in the management of shooting pain, for example: trigeminal neuralgia and the shooting element of neurogenic pain, such as post-herpetic neuralgia, diabetic neuropathy and similar conditions. Carbamazepine appears to be the most effective drug although there is a higher incidence of side-effects than with Sodium Valproate. Recently Gabapentin and Lamotrigine are enjoying popularity, either as "add on" drugs, or as sole agents. Further drug development of these types of agents might produce useful efficacy in the future.
ii) Tricyclic antidepressants are one of the most commonly used analgesics in pain clinics. This is not for the specific antidepressant action, but is more associated with the activation of pain inhibitory pathways. This appears to be less of a feature with the tetracyclic agents, and has meant that their usage in chronic pain has as yet remained unproven. This is of course is disappointing as the side-effect profile is significantly better. The sedative effect of Amitriptyline can be harnessed to good usage by giving the tablet one or two hours before retiring, and it should not be used during the day.
ANALGESIC PAIN MANAGEMENT
In general, patients with pain can be given a trial of Paracetamol. An appropriate non-steroidal can be used if there is an inflammatory process, and continued if these are effective and if side-effects are minimal. The next optimal step in the analgesic ladder will be the use of agents like Tramadol, Dextropropoxyphene, or Dihydrocodeine, with long-acting preparations being ideal for chronic pain. At present, slow-release Tramadol would appear to be the most effective drug in chronic pain for this group of patients. If side-effects preclude its usage, one of the other agents can be considered.
Finally a small group of patients might be suitable for the use of opioids themselves.
In conjunction with this ladder, anticonvulsants and tricyclic antidepressants can be considered, for their specific and appropriate actions on shooting and burning pain, usually of neurogenic origin.
Whilst this has usually been attempted by the time a patient reaches a Pain Clinic, appropriate physiotherapy in the form of an exercise programme is almost always of benefit. A great deal of work needs to be done to validate conventional physiotherapy techniques; usage in acute pain appears to bring little benefit over the natural history of the condition, whilst in chronic pain it can often be of only short-term efficacy. However, functional rehabilitation programmes aimed at restoration of suppleness and muscle function do appear to be of very real benefit in the long term. Chiropractic manipulation has been shown to be effective in some studies, whilst ineffective in others. Again, patient selection and the technique of the manipulator are markedly variable and will alter efficacy a great deal.
Both acupuncture and TENS are exciting great controversy at the present time in the Western world; their long standing use for chronic pain is being questioned because (again) of the lack of evidence. This remains a controversial field, but both techniques appear to be relatively simple, fairly safe in appropriate hands and reasonably cheap. Acupuncture again is said to work on descending inhibitory pain pathways and also to stimulate endorphins (as well as the body's natural cortisone). Both positive and negative results have been shown in a bewildering variety of trials. There is certainly a powerful placebo effect, but there also seems to be a significant analgesic component, albeit this might last for only a very short period, and the benefits seen with many patients may be due to a reduction in distress and disability engendered by their interaction with the therapist.
Again it is difficult to find a wealth of hard evidence as to the efficacy of TENS, but a limited, albeit significant number of patients appear to get good benefit, and this appears in some studies to be better than placebo.
Dorsal column stimulation continues to excite interest. Clearly, this can be a useful therapy for moderate pain, especially if it encourages entry into a pain management programme-type approach.
The use of nerve blocks has also been criticised because of the lack of appropriate double-blind, randomised controlled trials. However, it must be appreciated that these are hard to carry out for non drug treatments, and in such a disparate group of patients as for instance those with low back pain and neurogenic pain. However, it is clear that trials are now being carried out and can show the efficacy of various treatments. On the whole I veer away from permanent lesions for patients with chronic non-malignant pain.
Facet joint denervations have been shown by Lord, Barnsley and Bogduk to be effective for both low back pain and neck pain resulting from whiplash injuries.
Efficacy and safety of epidural steroids have been investigated extensively and recent randomised controlled trials appear to show benefit for their use in limb pain and also in acute back pain or neck pain. It is essential for an appropriate dose to be used and for careful placement of the drug in the correct compartment. I would suggest the use of epidurography at least and the new technique of epiduroscopy is interesting, although as yet completely unproven.
It is understandable and tempting to think of a painful disc as the cause of a significant number of certain patients' symptoms, and the new technique of disc denervation is another therapy under review at present.
Pulsed radiofrequency has been recommended by Dutch authors, but as yet I fail to see the rationale or the scientific evidence which would lead me to embrace this technique. At least it appears to be side-effect free, although it is a potentially expensive treatment, especially if it is only a placebo!
The use of Botulinum Toxin for muscle spasm is also under investigation at the present time. Clearly the agent has a powerful muscle relaxant effect, which is present from two to six months. Also it appears a relatively safe drug. However a great deal of work needs to be done now to identify the appropriate patients for treatment with this fairly extensive compound.
If a nociceptive source is identified, then surgery may be appropriate. However, of all the many treatments for chronic pain, surgery could be said to be the most lacking in evidence-based medicine. The lack of efficacy of surgery for back pain has resulted in a greatly diminished number of operations being carried out for this condition in the West. Efficacy rates at two years and five years are disappointing. Even the management of acute disc pain in athletes in the United States has changed dramatically, with virtually no patients, providing they have no gross neurological deficit, having surgery merely for the symptom of pain. Again a functional exercise programme is offered even to the fittest of men, with resulting good benefit, long-term efficacy, and better quality of life.
Psychological techniques again need to be tailored to the individual patient and not offered piecemeal. Cognitive therapy is perhaps something that any good physician will do, in explaining to the patient the cause of the pain in less than the lurid terms sometimes adopted by a clinician. Knowledge of the natural history of conditions is essential. False promises lead to confusion and long-term disillusionment. Behavioural techniques are something adopted by any good therapist with rewards being given for re-establishment of function rather than expressions of pain and misery.
A skilled clinical psychologist is an invaluable and essential part of every Chronic Pain Unit, and a useful second opinion and source of help for any clinician who has any doubt as to the differential diagnosis and management of a particular patient. Techniques such as relaxation, hypnosis and bio-feedback have been shown to be effective, although again these can be time-consuming and therefore expensive, and long-term results can sometimes be disappointing.
It is quite clear that many patients improve a great deal on a multi-disciplinary pain management programme, with some getting a reduction in pain and others improving greatly on parameters of reduced distress and reduced disability.
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