RELIEF OF CHRONIC NON-MALIGNANT PAIN
Pain sensation & transmission
Psychological factors
Patients, pain histories and recording pain
Pain histories
Recording Pain
Chronic pain treatment
Figure 1: WHO analgesic ladder in acute and chronic pain
Figure 2: Treatment Methods
Non-opioid analgesics
Oral NSAIDs, combinations and others
Figure 3: League Table of number needed to treat (NNT) for postoperative pain
Comparisons
Topical NSAIDs
Opioids
Figure 4: Opioid titration to effect
Unconventional analgesics
Antidepressants
Table 2: Number-needed-to-treat (NNT) for some analgesic interventions in chronic pain
Anticonvdlsants
Others
Block Nerve Transmission
Reversible
Local Anaesthetics
Table 3: Common nerve blocks
Fibromyalgia
Intravenous regional sympathectomy
Epidural steroids and facet joint blocks
Table 4: Epidural corticosteroids for sciatica
Short-term relief
Long-term relief
Conclusion
Irreversible
Surgery
Alternatives
TENS, acupuncture
Physiotherapy and variants
Behavioural Management
Further Reading

RELIEF OF CHRONIC NON-MALIGNANT PAIN



Henry McQuay, DM

Clinical Reader in Pain Relief


Pain Research

Nuffield Department of Anaesthetics

University of Oxford

The Churchill

Oxford Radcliffe Hospital

Headington

Oxford OX3 7LJ, UK


Correspondence to Dr H J McQuay, Pain Research

Tel: +44 1865 226161

Fax: +44 1865 226160

email: henry.mcquay@pru.ox.ac.uk

This chapter should act as a signpost, directing the interested reader to the best evidence, and to systematic reviews and randomised controlled trials (RCTs) where available. The chapter takes the reader through the various interventions used in pain management, be they drugs, injections, operations, psychological or physical.


Pain sensation & transmission

The easiest way to think of pain in the nervous system is the idea of pain receptors and nerve cables dedicated to the transmission of pain signals, a hard-wired, line-labelled system. This view has always had obvious flaws. The return of pain after an initially successful cordotomy, and the phenomenon of phantom limb pain are two examples. In a hard-wired line-labelled system the pain should not recur after the cordotomy and patients should not feel pain in a limb as they did before the accident or amputation. Such flaws mean that the simple view of a 'passive' nervous system does not explain all that we see.


For most acute pain the idea of specific cables whose transmission can be blocked is reinforced by the fact that you can perform herniorrhaphy (painlessly) by using local anaesthetic block or indeed a regional block. The receptors and cables of that region are temporarily disabled by the local anaesthetic, and no pain message gets through to the brain. In some chronic pain syndromes the inadequacy of this simple explanation is exposed. An example is phantom pain, because the painful foot or hand, the receptors and the cables, are no longer there. The concept of 'pain memory' in the spinal cord and brain has to be invoked.


The idea that the nervous system can change, or be 'plastic', has led to the use of the word plasticity, and this concept has had a major impact in both acute and chronic pain. The simplest idea is that a memory of a pain is made and stored in the nervous system. Preventing such a memory being laid down led to the idea of pre-empting postoperative pain; any pain after the operation would be easier to treat if the memory had been minimised. Long-term sequelae, such as the phantom pain which can occur after amputation, might also be prevented. One issue of importance for treatment is at what level of the nervous system such memories might be stored. If the memory is stored at a 'central' level, for instance in the brain, then attacking the pain in the leg or arm where it originated might not do any good. The memory might be held centrally but require continued input from the periphery to sustain it. Attacking the pain in the leg or arm would then have some logic.


Many treatments, or interventions, are used to treat both acute pain and chronic pain. Chronic pain, not surprisingly, has more twists and turns, because its origins may be more complicated and because the nervous system if damaged or bombarded continuously by pain messages can behave strangely. The concept of plasticity has led to some interventions coming into fashion, and to some going out of fashion. Long-term measures, such as cutting the nerves thought to carry a particular pain message, are going out of fashion. The reasoning is that the nervous system will 'rewire', the pain will re-emerge, and may well be more difficult to manage than it was in the first place. Better drug control of difficult pains has also reduced the necessity for destructive procedures.


Psychological factors


Pain signals can be amplified or damped by endogenous influences such as mood or endorphins, or exogenous factors, drugs given or the circumstances of the injury. The classic damping-down scenario is the injured soldier who continues, despite a shattered leg, to get himself out of battle. Conversely a stubbed toe when you are tired and miserable is immeasurably more painful than the same injury on a cheerful morning. In chronic pain it is sometimes very hard to disentangle depression from pain. Pain makes depression worse and depression makes pain worse. This pattern is all too familiar to those who manage back pain. The thinking clinician needs to deal with both the pain and the depression.


Patients, pain histories and recording pain


Surgical referrals to pain centres are usually requests to see a patient after surgery because of pain which has resisted conventional treatment and because further surgery is inappropriate. There are few objective signs which the doctor can use to judge the severity of reported pain. Pain is necessarily subjective. Many patients have no obvious (visible) handicap. The most important principle is that the patient and the doctor are best served if the doctor believes the patient's report. Their problems may be ill-understood, even disbelieved, at work and at home. Chronic pain changes people, affecting their personal and working lives, and ultimately their personalities. Often such changes are reversible with successful treatment. Much time and energy is wasted on procedures designed to 'catch the patient out'. Labelling patients as malingerers or the pain as psychogenic may be easier than admitting that there is no successful treatment. The differential diagnosis for many pain conditions includes both cancer and non-cancer causes.


Pain histories


The extra emphasis of a pain history compared with a normal medical history is summarised in Table 1:-



Asking whether sensation is normal in the painful area and whether the pain is shooting or stabbing in character may help to identify the pains variously known as dysaesthetic, deafferentation or neuropathic. It is important to distinguish these because they are unlikely to respond to conventional analgesics. These pains often have little pattern, but are less troublesome when the patient is distracted.


It is important to enquire specifically about the efficacy of each particular drug class. This information prevents the inept prescription of drugs which have failed previously, and may give important clues as to the kind of pain and its sensitivity to different classes of drug.


It is also important to know the dose size, frequency, duration of prescription and the side-effect problems for each drug which has been prescribed. Dose-response relationships apply with analgesics, and therapeutic failure should not be presumed if the dosage was inadequate; a good example is the use of carbamazepine in trigeminal neuralgia. Is the patient taking drugs other than analgesics? Anticoagulation, for instance, is not only an (almost) absolute contraindication to pain management by injection procedures, but also interacts with some anti-inflammatory drugs.


It is important to be sure whether nerve-blocks used previously were technically effective (e.g. did the patient have any numbness after an epidural which included local anaesthetic?), before dismissing them as of no help to this patient. Equally other measures, such as transcutaneous nerve stimulation, may not have been used correctly, and may succeed if the patient receives proper instruction in their use.


Recording Pain


For chronic pain, when patients are recording over long periods, we tend to use diaries with word categories, and ask about both pain intensity (none, mild, moderate or severe) and pain relief (none, slight, moderate, good or complete). Another useful scale is the patient's 'global report'. Using the same categories as the pain relief scale, this is a composite view encompassing both pain itself and any adverse effects of treatment. The clinician's global view is a notorious overestimate and should not be used.


Most important and simplest is the idea of including a binary scale because of its clinical relevance. The question is phrased in various forms, around the idea of "Is your pain at least 50% relieved?", to which the patient answers yes or no.


The argument for using pain charts as part of normal practice is to improve the quality of care. It is the fact of a chart rather than the form of the chart which is most important. These should be done together with vital signs, and can then be used for both clinical care and for audit.


Some index of function is necessary as a base-line so that improvement or deterioration may be monitored. Useful clinical outcome measures are notoriously difficult; using simple pain charts and indices of activity can work well.


Chronic pain treatment


This chapter uses systematic reviews when possible to provide the best available evidence for the various interventions used to relieve pain. The number-needed-to-treat (NNT) is used as the measure of clinical significance from quantitative systematic reviews. It shows the effort required to achieve a particular therapeutic target. NNT is treatment specific. It describes the difference between active treatment and control. The NNT is given by the equation



where:


IMPact = number of patients given active treatment achieving the target

TOTact = total number of patients given the active treatment

IMPcon = number of patients given a control treatment achieving the target

TOTcon = total number of patients given the control treatment


An NNT of 1 describes an event which occurs in every patient given the treatment but in no patient in a comparator group. This could be described as the 'perfect' result in, say, a therapeutic trial of an antibiotic compared with placebo. For therapeutic benefit the NNT should be as close as possible to 1; there are few circumstances in which a treatment is close to 100% effective and the control or placebo completely ineffective, so NNTs of 2 or 3 often indicate an effective intervention. For unwanted effects, NNT becomes the NNH (number-needed-to-harm), which should be as large as possible.


Figure 1: WHO analgesic ladder in acute and chronic pain







Figure 2: Treatment Methods







Most chronic pain is managed initially with analgesics, but may also involve nerve transmission block and alternative methods. Figures 1 and 2 show the simple comparison with acute pain and the alternatives. As acute pain wanes weaker analgesics are used. If chronic pain increases stronger ones are necessary.


The same analgesics, from non-steroidal anti-inflammatory drugs (NSAIDs) through to opioid, are used in chronic as in acute pain. If analgesics relieve the pain to an adequate extent, and with tolerable or controllable adverse effects, then there is little reason to use other interventions. If analgesics are ineffective other methods have to be considered. If analgesics are effective but cause intolerable or uncontrollable adverse effects then again other methods should be considered. The effectiveness and the adverse effects of the analgesics are critical.


We know from work with cancer pain that using analgesics according to the WHO ladder (Figure 1) can relieve pain for 80% of patients. For most of the 80% the relief will be good, for a minority it will only be moderate. This presumes that the pain is managed optimally, and we know from audit that this is often not the case. Optimal management requires that the correct drugs are available, and that they are given in the correct dose by the correct route and at the correct time. This needs staff who are well versed in the problems, and who are available to care for the patient. The second problem is the 20% of patients whose pain is not well managed by intelligent use of analgesic guidelines. The other treatment methods on Figure 2 are necessary to manage those for whom analgesics fail.


Non-opioid analgesics


Oral NSAIDs, combinations and others


Choosing the best analgesic for long term use involves the same decisions as in acute pain. Most comparisons are done using single doses, whereas patients with chronic pain take multiple doses. Figure 3 shows an evolving league table for analgesic performance after surgery.


Figure 3: League Table of number needed to treat (NNT) for postoperative pain






NNT for at least 50% pain relief over 4-6 hours in patients with moderate to severe pain, all oral analgesics except IM morphine, all single dose studies.



Ibuprofen 400 mg (and other NSAIDs analysed) will produce at least 50% relief of pain for one out of two postoperative patients, paracetamol 1 g for one out of four patients.


Although this efficacy league table (Figure 3) was derived from acute pain trials we believe it is also valid in chronic pain. The clear guideline is that the first choice is an oral NSAID if there is no contraindication. No single-dose trial has shown any efficacy advantage of one NSAID over another, although this does not fit well with patients' reports on multiple dosing of increased efficacy from NSAIDs with greater anti-inflammatory action. Gastric bleeding is a problem of chronic use. The risk of NSAID induced gastric bleeding is lowest with ibuprofen, and increases with increasing age. Prophylactic misoprostol or omeprazole should be considered for preventing NSAID associated gastrointestinal complications when age is greater than 75 years, cardiovascular disease, history of peptic ulcer or of gastrointestinal bleeding (NNTs to prevent one serious GI complication in one year 105, 58, 11 and 7 respectively). Acute renal failure can be precipitated in those with pre-existing heart or kidney disease, those on loop diuretics or those who have lost more than 10% of blood volume.


The efficacy dose-response curve for NSAIDs is flatter than the dose-response for adverse effects such as gastrointestinal symptoms, dizziness, and drowsiness. Increasing the dose to improve analgesia is therefore more likely to increase adverse effects than to improve analgesia.


There is an old adage that if patients can swallow it is best to take drugs by mouth. This is very pertinent for pain relief after surgery or trauma. Effective relief can be achieved with oral NSAIDs, and there is no evidence that NSAIDs given by injection perform better than the same drug at the same dose given by mouth.


Centrally-acting non-opioids include paracetamol, dipyrone and nefopam. Dipyrone is widely used in certain countries, and is an effective analgesic which can produce blood dyscrasias. The lack of comparative evidence makes it hard to rank its risk:benefit profile against the other analgesics.


Comparisons


NSAIDs alone produced as good analgesia as single or multiple doses of weak opioids alone or in combination with nonopioid analgesics. Adverse effect incidence and patient dropout rates were the same for multiple doses of NSAIDs or weak opioids in combination with nonopioid analgesics. Conversely there is little evidence that in osteoarthritis that NSAIDs are better than paracetamol or that weak opioids in combination with paracetamol are better than paracetamol alone.


Topical NSAIDs


Many doctors remain sceptical about the efficacy of topical NSAIDs. This may not be correct. Published RCTs on chronic pain conditions (mainly knee osteoarthritis) studied over 800 subjects treated with topical NSAIDs and 322 subjects who received placebo. The analgesic response for combined placebo treatment was 30%, and for combined topical non-steroidal anti-inflammatory preparations it was 63%. The number-needed-to-treat was 3.2 (2.6 - 4.1). Rubbing on a topical NSAID is much more effective than rubbing on a placebo.


Opioids


In chronic pain there are two particular problems with opioids. The first is that adequate doses are often not available or are not given, primarily because of fears of addiction. The second is that some (rarer) chronic pain states, particularly when the nervous system is damaged, may not respond fully to opioids.


The main reason that adequate doses are withheld by doctors or nurses is the fear of respiratory depression. Opioids used for people who are not in pain, or in doses larger than necessary to control the pain, can slow and indeed stop breathing. The principle is that the dose has to be titrated to the effect (Figure 4). The effect is pain relief. If the dose given has not produced pain relief (the patient is still complaining of pain), and it has all been delivered and absorbed, then it is safe to give another dose. This subsequent dose may be smaller than the first. If it too doesn't succeed then the process can be repeated.


Figure 4: Opioid titration to effect





The principle is that the dose has to be titrated to the effect. The effect is pain relief. Doses larger than necessary to control the pain can cause serious adverse effects. If the dose given has not produced pain relief because the patient is still complaining of pain, and it has all been delivered and absorbed, then it is safe to give another dose, which may be smaller than the first.


There is no compelling evidence that one opioid is better than another, but there is good evidence that pethidine has a specific disadvantage. Given in multiple doses its metabolite norpethidine can accumulate and act as a CNS irritant, ultimately causing convulsions. This is more likely when there is renal dysfunction. This toxic metabolite should preclude using pethidine when multiple doses are needed. The old idea that pethidine is better than other opioids at dealing with colicky pain is no longer tenable.


Morphine (and its family including heroin and codeine), has an active rather than a toxic metabolite, morphine-6-glucuronide. In renal dysfunction this metabolite can accumulate and result, because it is more active than morphine, in greater effect from a given dose. If you are, as you should be, titrating dose against effect, this will not matter. Less morphine will be needed. It can be a problem with unconscious patients being dosed by the clock, and whose renal function is compromised.


Opioids used for people who are not in pain can induce physical and psychological dependence. This does not happen to patients who receive them for pain relief, for instance after an operation or for severe pain from osteoporotic vertebral collapse. Some governments restrict medical availability on the grounds that if the drugs are available medically this will worsen the street addiction problem. There is no evidence for this. The casualties are patients who are deprived of adequate pain relief.


In chronic pain opioids are usually given by mouth. The dose is worked out by titration over a period of days, and then the drug is given regularly, not waiting for the pain to come back. Initial problems with nausea or dizziness commonly settle. If constipation is likely laxatives are given.


Patients who cannot swallow can try sublingual, transdermal or suppository dosing. Subcutaneous infusion, usually from a small (external) pump is used for terminal patients who cannot manage these other routes. Rarely the epidural route is used for combination infusion of opioid and local anaesthetic.


If patients' pain starts to increase the dose is increased. If sensible dose increases do not produce pain relief, or if increasing the opioid dose provokes intolerable or unmanageable adverse effects, then other methods have to be considered, either as well as the opioid or instead of it. A working rule is that if the pain is in a numb area, which is a marker for a damaged nervous system, we would be less confident that opioids would necessarily produce pain relief, and our threshold for using other strategies would be lower.


Unconventional analgesics


Unconventional analgesics are drugs which have other indications in other medical settings, and are not normally thought of as analgesics. Treating chronic pain in a tertiary hospital setting we use these drugs for about one third of our patients. The hall-mark is pain in a numb area, neuropathic pain.


When the patient has symptoms and signs of nervous system damage in the area of their pain we expect the response to conventional analgesics to be reduced. Conventional analgesics have often failed already, which is why the patient has been referred. If not, we try the conventional drugs, before we embark on empirical testing to see if any of the unconventional analgesics can provide relief.


Antidepressants


Antidepressants work on the nervous system to relieve depression. We use them in much lower dosage (about half), and we use them to relieve pain. Classically they were used to relieve pain that was burning rather than shooting in character, and anticonvulsants were used for shooting pains. Now we tend to use antidepressants as first line for both types of pain, because we have greater success and because we believe the antidepressants cause fewer adverse effects (but see below).


We use low doses (median 75 mg amitriptyline nocte, maximum 150 mg) compared with those used to control depression. The pain relieving effect happens, if it is going to happen, well within a week, whereas 10 days is the minimum often quoted for an antidepressant effect. The older (tricyclic) antidepressants seem to be better than the selective serotonin reuptake inhibitors as analgesics. The simplest analogy is that these older drugs are like shotguns, acting on multiple transmitter pathways, whereas the newer ones are more like rifles, designed as they are to be more selective and affect only one pathway.


Table 2: Number-needed-to-treat (NNT) for some analgesic interventions in chronic pain





Anticonvulsants


Anticonvulsants have been used for many years to treat the shooting pains of trigeminal neuralgia and of diabetic neuropathy. How they work has never been clear. The catch-all explanation was that they stabilised nerve membranes, preventing them carrying spurious messages. The current fashionable explanation is that these drugs acting as antagonists on the N-methyl D-aspartate (NMDA) mechanism.


Anticonvulsants can provide good relief in neuropathic pain (NNT of 2-3, Table 2). Doses required for analgesic effect are close to the anticonvulsant dosing range, and carry a perceived burden of adverse effects. The systematic reviews suggest that there is little difference between the antidepressant and anticonvulsant adverse effects. Our main use is the traditional role in trigeminal neuralgia and diabetic neuropathy. We also use anticonvulsants in shooting pain which does not respond to antidepressants. Two examples are phantom limb pain and pain in the head and neck due to tumour.


Others


Clonidine and other alpha-2 adrenergic agonists have analgesic effects, both in conventional pain and in neuropathic pain. They extend the duration of local anaesthetic effect and have a synergistic effect with opioids. Their clinical utility is limited by the adverse effects of sedation and hypotension. In neuropathic pain cancer pain epidural clonidine was effective. Baclofen is used by intrathecal pump to treat the painful spasms of cerebral palsy. Ketamine and dextromethorphan, both drugs with NMDA antagonist action, are being used in severe neuropathic pain.


Block Nerve Transmission

Reversible


Local Anaesthetics


Local anaesthetics block nerve conduction reversibly. When the local anaesthetic wears off the pain returns. That is the pharmacologically correct statement, but another old saying, that a series of local anaesthetic blocks can be used to "break the cycle" of pain and effect a cure, now has some empirical support, even if we do not understand the mechanism. Arner and colleagues showed that the duration of pain relief could far outlast the duration of local anaesthetic action, and that prolonged relief could result from a series of blocks. Local anaesthetic blocks can thus be diagnostic and therapeutic. Diagnosis of pain for instance from a 'trapped' lateral cutaneous nerve of thigh can be confirmed by local anaesthetic block, and a series of blocks may prevent pain recurring.


Pain clinics use such blocks commonly, for shoulder pain, for intercostal neuralgia, for rectus sheath nerve entrapment, postoperative scar pains and other peripheral neuralgias (Table 3). What is not clear is the extent to which adding steroid to the local anaesthetic makes a difference, either prolonging the duration of effect of a particular procedure or increasing the chance of success of a series of blocks.


Table 3: Common nerve blocks






Fibromyalgia


Similar injections are done for the trigger points of fibromyalgia, but there do not appear to be any controlled comparisons of injections with other treatments.


Intravenous regional sympathectomy


Intravenous regional sympathetic blocks (IRSBs) are used widely in patients with reflex sympathetic dystrophy (RSD). A systematic review of 7 RCTs of IRSBs found that none of the 4 guanethidine trials showed significant analgesic effect. Two reports, one using ketanserin and one bretylium with 17 patients in total, showed some advantage of IRSBs over control. Adding guanethidine in IRSBs does not appear to be more effective than local anaesthetic alone.


Epidural steroids and facet joint blocks


Two other common (for back pain) pain clinic procedures are epidural steroid injection and facet nerve blocks. Two systematic reviews have addressed the effectiveness of epidural steroid injections for sciatica and back pain. Both examined the randomised controlled trials published up to the end of 1994.


The analysis by Koes and colleagues from Amsterdam goes into great depth examining methodological quality of the trials and how this has been scored by the reviewers. This type of review is, frankly, disappointing and does not produce any meta-analytic judgements on which to work, and few enlightening ideas about the future research agenda other than some anodyne comments about possible trial design.


The best that this review can do is to tell us that, of the four studies with the highest methodological quality assessed by their particular scoring system, two had positive outcomes for epidural steroids (judged by their authors) and two had negative outcomes.


In contrast, a meta-analysis of the same trials by Watts and Silagy is an important step forward in showing that epidural corticosteroids have an analgesic effect on sciatica compared with control. Their analysis, using odds ratios, answered the question "Do epidural steroids work?".


To address the question "How well do they work?", to try to assess the extent of the benefit given by the steroids we re-analysed their data, adding a new trial by Carette et al, and calculated the NNT (Table 4), for at least 75% pain relief for short-term outcomes (1 - 60 days) and at least 50% pain relief for long-term outcomes (12 weeks to one year).


Table 4: Epidural corticosteroids for sciatica




Short-term relief


There were eleven trials which gave short-term relief data (more than 75% pain relief), with 319 patients given epidural steroids, and 345 given placebo. Only three of these studies were themselves statistically significant, but overall there was a statistically significant benefit (1.5 with 95% confidence intervals 1.2 to 1.9). The NNT for short-term (1 to 60 days) greater than 75% pain relief from the ten trials with short-term outcomes combined, was just under 7.3, with 95% confidence intervals from 4.7 to 16. This means that for 7 patients treated with epidural steroid one will obtain more than 75% pain relief short-term who would not have done had they received the control treatment (placebo or local anaesthetic).


Long-term relief


There were six trials which gave long-term relief data with 315 patients given epidural steroids, and 395 given placebo. Only one of these studies was itself statistically significant, but overall there was a statistically significant benefit (1.3 with 95% confidence intervals 1.1 to 1.5).


The NNT for long-term (12 weeks up to 1 year) improvement from the six trials combined, was about 13 for 50% pain relief, with 95% confidence intervals from 6.6 to 314. This means that for 13 patients treated with epidural steroid one will obtain more pain relief over this longer term period who would not have done had they received the control treatment (placebo or local anaesthetic).


Conclusion


These NNT values at first sight appear disappointing. Here is an intervention which shows statistically significant improvement compared with control, and yet the clinical benefit, the number-needed-to-treat for one patient to reach the chosen end-point, is 7 for short-term benefit and 13 for long-term. The short-term end-point, however, is quite a high hurdle. Using an easier hurdle of 50% relief rather than 75%, the 'best' NNT achieved by drug treatment of neuropathic pain was just under 3. Patients may choose the epidural if it means they do not have to take medication, particularly if it gives a higher level of relief, even though there is a 1 in 7 chance of this level of response.


The long-term NNT of 13 is perhaps not surprising. Occasional patients in most clinics report a 'cure' as a result of a steroid epidural, but the majority of epidural steroid successes return for repeat epidurals. That one patient has relief lasting between 12 weeks and a year for twelve treated with epidural steroid fits with experience.


For patients with chronic disease, and in this case chronic painful disease, interventions may be attractive even if their success rate is far lower than would be acceptable in, say, the management of postoperative pain. This means that the interpretation of measures of clinical benefit, such as NNTs, has to be context-dependent.


There is considerable current controversy about the potential for epidural steroid to produce long-term neurological sequelae. Intrathecal injection of steroid can produce neurological sequelae. It is therefore important that intrathecal injection is avoided.


Classically facet joint injection with local anaesthetic and steroid is indicated when pain is worse when sitting, and pain is provoked by lateral rotation and spine extension. Recent studies suggest that whether or not the injection is actually in the facet joint makes little difference, and indeed cast some doubt on long-term utility. Short-lived success (less than six weeks) with local anaesthetic and steroid is said to be improved by use of cryoanalgesia or radiofrequency blocks to the nerves to the joints.


Irreversible


The destructive procedures are aimed at cutting, burning or damaging the nerve fibres carrying the pain signals. The flaw in the logic is that the nervous system can all too often rewire, finding a way around the lesion. If that happens, and the pain returns, then it may be even more difficult to manage - severe neuropathic pain can result. In general neurolytic blocks in non-malignant pain are not recommended, because they do not last forever, and recurrent pain may be more difficult to manage, and because of the morbidity. In cancer pain these neurolytic block procedures do have a place, when there is a prognosis of less than three months, or where alternatives such as painstaking drug control or long-term epidural infusion are not possible. Similar distinction between cancer and non-cancer pain holds for coeliac plexus block in pancreatic pain. Pain associated with pancreatic cancer responds well to coeliac plexus block, and it may also help those with abdominal or perineal pain from tumour in the pelvis. In chronic pancreatitis results are much less convincing.


The limitation is the potential for motor and sphincter damage. This risk is greater with bilateral and repeat procedures, and greater the lower the cord level of the block. Extradural neurolytics have limited efficacy. While claims have been made that the paravertebral approach is preferable, patchy results may be attributed to unpredictable injectate spread. Results with epidural infusion of a combination of local anaesthetic and opioid are superior to neurolytic blocks, providing good analgesia with minimal irreversible morbidity.


Surgery


The relevant neurosurgical interventions for chronic pain include dorsal column stimulation, rhizotomy, cordotomy and dorsal root entry zone (DREZ) lesions. The indications are usually non-malignant neuropathic pain which has failed to respond to pharmacological measures. The difficulties of trials of uncommon surgical procedures are well known. These procedures are usually documented by glowing case series. Longer term outcomes may not be so good.


Alternatives


TENS, acupuncture


The rationale for transcutaneous nerve stimulation (TENS) is the gate theory. If the spinal cord is bombarded with impulses from the TENS machine then it is distracted from transmitting the pathological pain signal. We know from systematic reviews that TENS has limited efficacy in acute (and postoperative) pain, and also in labour pain. Most trials in chronic pain are of very short duration (low 'dose') TENS. and the pooled results are unconvincing.


What we do know is that attention to detail makes considerable difference to TENS efficacy in chronic pain, and that the dose of TENS may need to be much greater than tested in the trials to date. Patients need to be told that it is useless expecting success unless the machine is connected for at least an hour at a time. They need to be told where to put the electrodes, how to put them on, how to manipulate the stimulus to best advantage, and indeed to turn the machine on.


At least three systematic reviews discuss acupuncture in chronic non-malignant pain. These show an effect in poor quality trials, but that effect in clinical practice is often short-lived (3 days), and is therefore expensive in time. It is difficult to know what is the real place of acupuncture, like other complementary interventions, because of the lack of trials comparing complementary with mainstream procedures.


Physiotherapy and variants


Pain clinics keep a very open mind about other interventions. If patients benefit from alternatives we are only too pleased. The evidence from back pain however suggests that on rigorous outcome measures physiotherapy and other forms of manipulation have but limited success. Such analyses often did not include any measure of quality of life. If they make the patient feel better and they are cheap then it is a decision for the third party payer whether or not these physiotherapy manoeuvres should be offered.


Behavioural Management


Back schools through to behavioural management programmes offer a range of help for patients, help to cope with their (usually back) pain problems. Making decisions about the benefits of psychologically-based treatments of medical problems is not easy, and especially difficult to compare with other treatments and to measure relative benefit and cost. Patients whose pain has proved intractable to all reasonable medical and other interventions are chronic consumers of health care - GP or hospital clinic time, analgesic and psychotropic drugs, repeated admissions and sometimes surgery. If rehabilitation treatment enables these patients to carry on more satisfying lives with minimum medical help, how can it be most effectively and economically offered? The inpatient and outpatient treatment options are reviewed in.

Further Reading

Source for systematic reviews of pain treatments

McQuay HJ, Moore RA. An evidence-based resource for pain relief. Oxford: Oxford University Press, 1998.

NSAID adverse effects and efficacy

Henry D, Lim LL-Y, Rodriguez LAG et al . Variability in risk of gastrointestinal complications with individual non-steroidal anti-inflammatory drugs: results of a collaborative meta-analysis. British Medical Journal 1996; 312:1563-6.

Yeomans ND, Tulassay Z, Juhasz Lea. A comparison of omeprazole with ranitidine for ulcers associated with nonsteroidal antiinflammatory drugs. N Engl J Med 1998; 338:719-26.

Hawkey CJ, Karrasch JA, Szczepanski Lea. Omeprazole compared with misoprostol for ulcers associated with nonsteroidal antiinflammatory drugs. N Engl J Med 1998; 338:727-34.

Silverstein FE, Graham D. Y., Senior JR et al . Misoprostol reduces serious gastrointestinal complications in patients with rheumatoid arthritis receiving nonsteroidal anti-inflammatory drugs. Annals of Internal Medicine 1995; 123(No. 4):241-9.

Shield MJ, Morant SV. Misoprostol in patients taking non-steroidal anti-inflammatory drugs. British Medical Journal 1996; 312:846.

Eisenberg E, Berkey CS, Carr DB, Mosteller F, Chalmers TC. Efficacy and safety of nonsteroidal antiinflammatory drugs for cancer pain: a meta-analysis. J Clin Oncol 1994; 12(12):2756-65.

Clonidine

Eisenach JC, DuPen S, Dubois M, Miguel R, Allin D. Epidural clonidine analgesia for intractable cancer pain. The Epidural Clonidine Study Group. Pain 1995; 61(3):391-9.

Nerve Blocks

Arner S, Lindblom U, Meyerson BA, Molander C. Prolonged relief of neuralgia after regional anesthetic blocks. A call for further experimental and systematic clinical studies. Pain 1990; 43(3):287-97.

Epidurals for sciatica

Koes BW, Scholten RPM, Mens JMA, Bouter LM. Efficacy of epidural steroid injections for low-back pain and sciatica: a systematic review of randomized clinical trials. Pain 1995; 63:279-88.

Watts RW, Silagy CA. A meta-analysis on the efficacy of epidural corticosteroids in the treatment of sciatica. Anaesthesia and Intensive Care 1995; 23:564-9.

Carette S, Leclaire R, Marcoux S et al . Epidural corticosteroid injections for sciatica due to herniated nucleus pulposus. N Engl J Med 1997; 336(23):1634-40.

Facet Joint Injections

Lilius G, Laasonen EM, Myllynen P, Harilainen A, Grönlund G. Lumbar facet joint syndrome. Journal of Bone and Joint Surgery 1989; 71:681-4.

Carette S, Marcoux S, Truchon R et al . A controlled trial of corticosteroid injections into facet joints for chronic low back pain. New England Journal of Medicine 1991; 325:1002-7.

Coeliac Plexus

Eisenberg E, Carr DB, Chalmers TC. Neurolytic celiac plexus block for treatment of cancer pain: a meta-analysis. Anesth Analg 1995; 80(2):290-5.

TENS

Reeve J, Menon D, Corabian P. Transcutaneous electrical nerve stimulation (TENS): a technology assessment. International Journal of Technology Assessment in Health Care 1996; 12:299-324.