Management of Chronic Pain

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Management of Chronic Pain

Recent advances in the understanding of the fundamental mechanisms involved in the transmission and modulation of noxious impulses have significantly extended the range of assessment tools and treatments clinicians offer to patients with pain. The majority of medical pain specialists in the UK are anaesthetists. Historically, anaesthetists have been responsible for the relief of pain in the perioperative period and have developed skills in percutaneous neural blockade. This expertise, developed originally with local anaesthetics, was then extended to neurolytic agents. Initially, pain clinics started as nerve-blocking clinics and most pain management clinics continue to be directed by anaesthetists who now have access to a formal training programme supervised by the Faculty of Pain Medicine of the Royal College of Anaesthetists, and specialist recognition. However, with increasing awareness of the complexity of the pain experience, there has been recognition that other healthcare professionals have a significant role in the management of patients with chronic pain. A multidisciplinary approach involving anaesthetists, other healthcare professionals, such as psychologists, physiotherapists, occupational therapists, nurse specialists, and other medical practitioners, is the preferred management model for people with pain. Evidence-based practice is now firmly established in clinical decision-making, particularly in formulating guidelines and consensus documents. Pain management clinics are available in most hospitals in the United Kingdom, with local variation in the services offered. Some offer specialist clinics for specific conditions (e.g. pelvic pain clinic, paediatric pain clinic) or treatments (e.g. spinal cord stimulators).

Current health trends are supporting the delivery of pain management services in primary care and in the community, because many patients can be managed in a primary care setting without needing to be referred to hospital. There is an increasing trend to involve the patient as an active participant of treatment and to include self-management strategies as part of the management plan.

DEFINITIONS OF PAIN AND RELATED TERMS

Pain: ‘an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage’ (The International Association for the Study of Pain, http://www.iasp-pain.org/AM/Template.cfm?Section=Pain_Definitions). This definition emphasizes that pain is not only a physical sensation but also a subjective psychological event. It accepts that pain may occur in spite of negative physical findings and investigations. Pain has sensory, cognitive and motivational-affective dimensions and has been described as a biopsychosocial experience, as illustrated in Figure 46.1. This must be taken into account when assessing and planning a treatment strategy for the patient with pain.

FIGURE 46.1 An illustration of pain as a biopsychosocial phenomenon.

Acute pain: pain associated with acute injury (including surgery) or disease.

Chronic or persistent pain: pain that either occurs in disease processes in which healing does not take place or persists beyond the expected time of healing – arbitrarily 3 months.

Pain management: a multidisciplinary approach to the assessment and treatment of patients with (acute and chronic) pain.

Pain management programme: a cognitive-behavioural programme for patients with persistent pain and disability.

Pain medicine: the diagnostic and therapeutic activities of medical practitioners.

Chronic pain syndrome: a term used to describe a constellation of pain and other symptoms of complex aetiology associated with Sternbach’s 6 Ds:

Dramatization of complaints

Chronic pain syndrome can adversely affect the patient in various ways, including depressed mood, fatigue, reduced activity and libido, excessive use of drugs and alcohol, dependent behaviour and disability out of proportion to impairment. It does not respond to the medical model of care and is best managed with a multidisciplinary approach.

THE PARADIGM OF PAIN

Pain management concerns postoperative, acute and chronic pain and cancer-related symptom control in children and adults. A joint report of the College of Anaesthetists and the Royal College of Surgeons of England highlighted the need to improve standards of postoperative pain management and many hospitals have established acute pain teams. However, many hospitalized patients suffer from acute non-postoperative pain. This may be caused by trauma, burns or acutely painful medical conditions (e.g. cardiac pain, osteoporotic vertebral collapse). Some medical conditions may cause recurrent acute painful episodes such as sickle-cell crisis or acute exacerbations of chronic pancreatitis. Unrelieved acute pain may lead to chronic pain. Chronic pain is a complex biopsychosocial phenomenon and a single pathophysiological explanation is not available for many chronic nonmalignant pain states. Palliative care services may refer cancer-related pain problems to the anaesthetist for management as a hospital inpatient, an outpatient, in a hospice or in the home. There are many common areas within the management of acute and chronic pain, and pain is increasingly viewed as a continuum rather than two separate entities, with subsequent merging of management techniques and staff.

Postoperative, acute, recurrent, persistent and cancer-related pain occurs in children. Difficulties in pain assessment and unsubstantiated fears and myths regarding pain and its treatment in children have led to suboptimal management. Recommendations for the management of pain in children have been published.

EPIDEMIOLOGY OF CHRONIC PAIN

The prevalence of chronic pain within the general population has proved difficult to estimate because of variations in the populations studied, the methods used to collect data and the criteria used to define chronic pain. Recent data have suggested that the prevalence of chronic pain in the UK is 13%, i.e. about 1 in 7 of the population. Chronic pain is the presenting complaint in 22% of primary care consultations and is estimated to account for 4.6 million GP visits per year. Patients with persistent pain consult their GPs five times more frequently than those without.

Untreated pain may reduce quality of life for sufferers and carers, resulting in helplessness, isolation, depression and family breakdown. Many patients with persistent pain have significant functional, social and financial consequences. Forty-nine percent take time off from work, 25% lose their jobs, 22% develop depression, 44% have their concentration affected and 56% have disturbed sleep.

Pain is the second commonest cause of days off work through sickness, accounting for 206 million working days lost in the UK in 1999–2000. It is the second commonest reason for people to be given Incapacity Benefit and £3.8 billion is spent per year on Incapacity Benefit for those in pain. The cost of back pain was £12.3 billion (22% of UK health expenditure) – mainly due to work days lost.

Pain is experienced by 20–50% of patients with cancer at the time of diagnosis and by up to 75% of patients with advanced disease.

CLASSIFICATION OF PAIN

Pain may be classified according to its aetiology.

In complex regional pain syndrome (CRPS) type 1, minor injuries, including mild soft tissue trauma or a fracture, precede the onset of symptoms without any overt nerve lesion (Fig. 46.2). CRPS type II develops after injury to a peripheral nerve. Pain is the prominent feature and is characteristically spontaneous and burning in nature and associated with allodynia (abnormal sensitivity of the skin) and hyperalgesia. Autonomic changes may lead to swelling, abnormal sweating and changes in skin blood flow. Atrophy of the skin, nails and muscles can occur and localized osteoporosis may be demonstrated on X-ray or bone scan. Movement of the limb is usually restricted as a result of the pain, and contractures may result. Treatment is directed at providing adequate analgesia to encourage active physiotherapy and improvement of function. In cases with sympathetically maintained pain, sympathetic nerve block may be part of this treatment strategy.

FIGURE 46.2 Complex regional pain syndrome type I following Colles’ fracture.

MANAGEMENT OF CHRONIC PAIN

Patients present with pain as a result of many different pathological processes. Some examples of common painful conditions are listed in Table 46.1.

TABLE 46.1

Some Common Painful Conditions

Malignant Aetiology

Primary tumours

Metastases

Nonmalignant Aetiology

Musculoskeletal

Back pain

Osteoarthritis

Rheumatoid arthritis

Osteoporotic fracture

Neuropathic

Trigeminal neuralgia

Postherpetic neuralgia

Brachial plexus avulsion

Radicular pain of spinal origin

Peripheral neuropathy

Chronic regional pain syndrome (CRPS)

Visceral

Urogenital pain

Pancreatitis

Post-surgery

Phantom pain

Stump pain

Scar pain

Post-laminectomy

Ischaemic

Peripheral vascular disease

Raynaud’s phenomenon/disease

Intractable angina

Headaches

Cancer treatment-related: e.g. post-surgery, post-chemotherapy, post-radiotherapy pain

Assessment

Comprehensive assessment of patients with pain is a vital first step. Pain is generally thought of as a symptom rather than a disease in its own right. Efforts should be made to investigate, diagnose and, if possible, treat the underlying cause of the pain before using empirical pain-relieving techniques. However, there is now a growing body of animal and human evidence that chronic pain may involve increased sensitivity of spinal cord neurones and changes in the spinal cord and the brain, which can be responsible for increased pain. Thus, there has been some support for persistent pain to be viewed as a condition in its own right.

Pain History

The key elements of a pain history should be ascertained using a structured interview. The interview includes assessment of the pain, the effect of pain on the patient’s mood and also the impact of the pain on quality of life and functioning. Many patients with pain become physically deconditioned and their mood can deteriorate. Both factors may contribute to the pain experience. Assessment can be recorded and audited using tools such as the Brief Pain Inventory.

Key elements in a pain history include:

mode of onset

location and radiation, either verbally or graphically using a pain diagram

frequency

aggravating factors

relieving factors

intensity, e.g. verbal rating scale, visual analogue scale, faces pain scale (children)

quality, to determine possible somatic or neuropathic aetiology, e.g. burning, shooting; validated screening tools such as The Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) pain scale can be used

previous treatments

current medication (analgesics and others)

concurrent medical illness

basic psychological assessment to include mood, coping skills, pain beliefs and self-reported disabilities; a Hospital Anxiety and Depression (HAD) scale can assist as a screening tool but if full psychological evaluation is indicated, it should be performed either by a psychiatrist or by a clinical psychologist, preferably one who is an integral member of the pain management team

patient’s own ideas as to causation

family and social history

impairment and functionality (Brief Pain Inventory)

Quality of Life, e.g. EQ-5D as a standardized instrument for use as a measure of health outcome

expectations of treatment.

Many patients, especially the elderly and those with malignancy, have more than one site of pain and separate histories should be taken for each complaint because their aetiologies may differ. Particular care and skill are needed when taking a pain history from children and the elderly.

Physical Examination

A physical examination relevant to the pain complaint should be performed and may include a full musculoskeletal or neurological assessment. It may involve a vaginal or rectal examination. Signs implicating involvement of the sympathetic nervous system including vasomotor, sudomotor and trophic changes should be considered. Physiotherapy assessment may be part of the initial screening interview.

Investigations

Additional laboratory, radiological and electrophysiological tests may be needed for full evaluation.

Chronic pain affects not only the patient, but also the family. Some patients with chronic pain become depressed and anxious, and lose their job, and financial and social status. Their relationships may deteriorate and it may be important to interview the patient’s relatives or significant others with the patient to assess the impact of the pain on family life.

Explanation

Chronic pain is a complex phenomenon and often multifactorial in aetiology. The diagnosis, where possible, is based on the history, examination and the results of any investigations. Classification of the pain aids treatment decisions in some cases but many pains are of a mixed aetiology. The pain complaint and the results of any investigations should be discussed with the patient. This may involve an explanation that there is no obvious structural explanation for the pain, but impressing upon the patient that this is a reflection of our currently inadequate methods for imaging pain and does not imply that the pain is imagined. A patient-led problem list should be formulated and patient expectations for treatment should be explored and, if necessary, rationalized. The limitations of the medical model of disease for some chronic pain complaints should be explained.

Treatment

Total relief of persistent pain is rarely possible. Therefore, it is important that the patient is given information on strategies which can be employed to reduce the impact of the pain on their everyday life. These self-management strategies should include advice about the importance of remaining active, increasing fitness levels, planning and pacing all activities and avoiding over-activity/under-activity cycles. Self-management booklets, such as the Pain Tool-kit, can be given to patients.

A treatment plan should be formulated jointly with the patient after discussion of appropriate treatments, the potential benefits and side-effects of those options and the option of deciding against treatment. Several methods of treatment may be used in the same patient, either concomitantly or sequentially.

The range of interventions for chronic pain is shown in Figure 46.3.

FIGURE 46.3 Management pathway for patient in pain. (Adapted from Moore et al 2003)

Medication

Many patients in pain are prescribed analgesic drugs. The pharmacology of these agents is discussed fully elsewhere (see Ch 5) and only aspects of particular relevance to their use in chronic pain are mentioned below.

Cancer Pain

Approximately 75% of patients with advanced cancer develop significant pain before death. Most cancer pain responds to pharmacological measures, and successful treatment is based on simple principles that have been promoted by the World Health Organization and are extensively validated. Analgesic drugs should be taken ‘by mouth’, ‘by the clock’ (i.e. regularly) and ‘by the analgesic ladder’ (Fig. 46.4). Cancer pain is continuous and medication must be taken regularly. It is given orally unless intractable nausea and vomiting occur or there is a physical impediment to swallowing. The first step on the ‘analgesic ladder’ is a non-opioid, such as paracetamol, aspirin or a non-steroidal anti-inflammatory drug (NSAID). If this is inadequate, a weak opioid such as codeine is added. The third step is substitution of the weak opioid by a strong opioid. Inadequate pain control at one level requires progression to a drug on the next level, rather than to an alternative of similar efficacy. Adjuvant analgesics, such as tricyclic or SNRI antidepressants, NSAIDs or anticonvulsants, may be used at any stage.

FIGURE 46.4 The WHO analgesic ladder.

Using these strategies, pain may be controlled successfully in about 90% of patients with cancer pain without resorting to other interventions.

Paracetamol

Paracetamol 4 g daily is a better analgesic than placebo, but probably not as effective as NSAIDs. However, in the elderly patient, paracetamol may be useful because of its low side-effect profile.

Non-Steroidal Anti-Inflammatory Drugs

NSAIDs possess analgesic and anti-inflammatory action and are used widely in the management of mild to moderate pain. They are effective analgesics for pain from osteoarthritis, rheumatoid arthritis, dysmenorrhoea and bone metastases. NSAIDs are not without adverse effects, the most worrying of which are an increased incidence of gastric ulcers, adverse effect on renal function and a potentially increased thrombotic risk, which has resulted in the European Medicines Agency stating that NSAIDs should be used in the lowest effective dose for the shortest possible duration.

Topical NSAIDs also provide effective pain relief.

Opioid Analgesics

Non-Cancer Pain: Weak opioid drugs, e.g. dihydrocodeine, are useful for moderate pain. However, they may be taken in excess, and often with only little benefit, by the patient with chronic non-malignant pain. Treatment in the pain management clinic may involve weaning the patient off such medication.

The use of strong opioids in non-malignant pain is controversial. There are trials of opioids in non-cancer pain which do show evidence of efficacy of opioids over placebo. However, these studies are often selective with regard to the patient and are short in duration, i.e. up to 3 months. Other studies have concluded that chronic opioid therapy exacerbates psychological distress, impairs cognition and worsens outcome. There is also concern about opioid-induced hyperalgesia, immune function and fertility. The controversy is also compounded by the perceived risk of psychological dependence (addiction) and the poorly understood phenomenon of tolerance. The British Pain Society has published recommendations for the appropriate use of opioids for persistent non-cancer pain and also specific information for patients on this subject.

Opioid Drugs

Morphine is the strong oral opioid of choice. Immediate-release oral morphine, either in liquid or tablet form, is given as often as necessary in increasing dosage until pain is controlled. When the required daily dose has been established, it is usual to convert to sustained-release morphine tablets, which need to be taken only once or twice daily. In addition, immediate-release morphine elixir or tablets should be prescribed for breakthrough cancer pain. The dose of morphine necessary to treat breakthrough cancer pain is one-sixth of the total daily morphine requirement.

Education of the medical and nursing professions, and also the cancer patient and family, is still necessary to ensure that adequate doses of opioids are prescribed and taken. Healthcare professionals often overestimate the side-effects of morphine. Respiratory depression is uncommon when morphine is prescribed for cancer pain. Surveys have shown that patients are concerned about side-effects of morphine, especially tolerance, addiction, constipation and drowsiness. Tolerance does not appear to be a problem clinically. Disease progression may necessitate an increase in dose, but there is no upper limit to the dose of morphine in cancer pain and pain control is usually regained without difficulty. Addiction (psychological dependence) is very uncommon in patients with cancer pain, and if the pain is relieved by other means, such as radiotherapy or a nerve block, many patients will stop taking opioids. Physical dependence always occurs and patients should be warned not to stop opioids precipitously. Nausea and vomiting may occur when treatment with morphine is started and an antiemetic may be prescribed for the first week, but often it may then be stopped. Sedation and cognitive impairment may occur as the dose is increased but these usually resolve. There is no tolerance to the constipating effect of morphine and laxatives need to be taken regularly. A phenomenon of opioid-induced hyperalgesia has been described, in which the patient suffers increasing pain, often of a widespread nature. It is thought that opioid-induced hyperalgesia develops as a result of activation of spinal cord mechanisms. Clinically, tolerance and disease progression need to be ruled out. The treatment of opioid-induced hyperalgesia involves decreasing the dose of opioid, switching to another opioid or the use of centrally acting analgesics such as ketamine.

Efforts should be made to reassure cancer patients and relatives of the efficacy and safety of morphine analgesia in both short and long term to ensure that medication is taken regularly.

Alternative Opioids and Alternative Routes of Administration: Oxycodone hydrochloride is a semisynthetic congener of morphine. It is available as an immediate-release and a sustained-release preparation. It is approximately twice as potent as morphine (i.e. 5 mg of oxycodone is equivalent to 10 mg of oral morphine). Its advantage in renal failure is the lack of detectable clinically relevant active metabolites, therefore avoiding accumulation. Prolonged release oxycodone is available in combination with prolonged release naloxone to counteract constipation.

Hydromorphone is a semisynthetic opioid with a rapid onset and a shorter duration of action than morphine. It is more potent than morphine, with 1.3 mg of hydromorphone being equivalent to 10 mg of morphine. Immediate-release, sustained-release preparations and parenteral preparations are available.

Methadone is a potent opioid analgesic and also possibly an N-methyl-D-aspartate (NMDA) receptor antagonist. Methadone is absorbed rapidly by the oral route and has a long half-life which may range from 13 to 51 h. Initial dosing must be monitored carefully because relatively small doses of methadone may be needed in comparison with the previous opioid dose. When repeated doses are given, the drug accumulates and after the first few days, the frequency of administration may need to be reduced to two or three times daily. Methadone should be considered a third-line drug indicated for cancer pain which appears poorly responsive to morphine, diamorphine, fentanyl, oxycodone or hydromorphone in spite of dose escalation and the use of adjuvant drugs. Methadone is available as tablets, linctus and injection.

Transdermal Drug Delivery: If a patient is unable to take medication by mouth, there are various alternative routes for opioid administration. A transdermal drug delivery system has been developed for fentanyl and buprenorphine. Fentanyl patches are applied to the skin and drug from the reservoir diffuses through the rate-controlling membrane and forms a subcutaneous depot from which the drug is taken up into the circulation. There is wide variation in absorption rates and time to steady-state serum concentrations of fentanyl. After removal of the patch, the terminal half-life has been shown to be 17 ± 2.3 h, indicative of the time taken for the drug to clear from the subcutaneous depot. Transdermal fentanyl is available in patches which deliver 12.5, 25, 50, 75 or 100 μg h^–1 of fentanyl. They should be placed on unbroken skin, usually on the upper body, and need to be changed every 72 h. An appropriate dose of immediate-release morphine or a buccal or transnasal fentanyl preparation should be prescribed for breakthrough pain.

Buprenorphine patches are matrix patches in which buprenorphine is incorporated within an adhesive matrix, allowing constant release of buprenorphine into the systemic circulation at a predetermined rate over a minimum of 72 h. The dose of buprenorphine delivered is dependent upon the amount of drug held in the matrix and the area of the patch. Patch strengths available are 5, 10, 20, 35, 52.5 and 70 μg h^–1 and patches should be applied either weekly or twice weekly, depending on the dose.

Pharmacokinetic data are of the utmost importance when considering changing medication from an opioid delivered by patch technology to an oral or parenteral opioid or vice versa. Patches are suitable for patients who cannot, or prefer not to, take oral medication or who are intolerant of morphine. However, the delay in onset of analgesia makes them unsuitable for treatment of acute pain. A table showing morphine equivalent doses of a variety of patches is available in the British Pain Society booklet ‘Opioids for persistent pain’.

Subcutaneous Administration: Continuous subcutaneous administration is another alternative method of administration if oral medication cannot be taken. A small, portable battery-operated syringe driver fitted with a 20 mL syringe containing the total daily opioid dose is usually used. Because of its greater solubility, diamorphine is the drug of choice in the UK for this route of administration. A conversion ratio of 3 mg oral morphine to 1 mg subcutaneous diamorphine is used.

Spinal Administration: Opioids may be administered spinally, either epidurally or intrathecally, for:

patients whose pain is controlled effectively by oral opioids but who suffer intolerable unacceptable side-effects, such as drowsiness or vomiting

patients whose pain cannot be controlled by the use of oral or systemic opioids.

Only a small proportion (less than 2%) of patients with cancer pain are candidates for spinal opioids. Much smaller doses of drug are required when given spinally and thus side-effects are minimized. The daily dose of morphine via the epidural route is 1/10 of the oral 24-h dose and the intrathecal dose is 1/10 of the epidural dose. Contraindications to the insertion of a spinal catheter are similar to those in the acute situation. Side-effects, such as respiratory depression, itching and urinary retention which cause such concern in the opioid-naïve patient are rare in cancer patients who have been chronically exposed to systemic opioids.

The field of spinal opioid therapy is sufficiently new that guidelines for selection of route (intrathecal or epidural), choice of drug (opioid or opioid/local anaesthetic combination), administration protocol (intermittent bolus or continuous infusion) and equipment (tunnelled or totally implanted catheter and reservoir) are still being formulated.

Before introducing this technique, it is essential to devise formal protocols and an education programme for hospital, hospice and primary care nurses and doctors to facilitate management of the patient in any of these settings.

Co-Analgesics

These are drugs which have primary indications other than pain but are analgesic in some painful conditions. Full explanation regarding this must be given to the patient. The National Institute for Health and Clinical Excellence (NICE) has recognized the analgesic properties of these drugs.

Anticonvulsants: Anticonvulsants are used in the treatment of neuropathic pain. The precise mechanism of action varies among different anticonvulsants. For example, it is thought that carbamazepine blocks sodium channels and that gabapentin and pregabalin act on the α₂δ subunit of the calcium channel. Therefore, if one anticonvulsant at maximum dosage is ineffective, then it is worthwhile trying another. Gabapentin, pregabalin, carbamazepine, oxcarbazepine, lamotrigine and phenytoin are used in neuropathic pain and trigeminal neuralgia.

In a variety of neuropathic pains, anticonvulsants have a number needed to treat (NNT) of less than 5 for at least 50% relief of pain, indicating that they are moderately effective for some patients. Data from studies show that for every patient who benefited, one had a minor adverse effect but continued with the treatment. Sedation, ataxia and weight gain are common side-effects of these drugs and may limit dose escalation, especially in the elderly.

Tricyclic and SNRI Antidepressants: Tricyclic and SNRI antidepressants have a role in the management of pain, independent of their effect on mood. Tricyclic drugs and SNRIs are postulated to act as analgesics by reducing the reuptake of the amine neurotransmitters noradrenaline and serotonin into the presynaptic terminal, increasing the concentration and duration of action of these substances at the synapse and thereby enhancing activity in the descending inhibitory pain pathway. Tricyclics also block sodium channels and suppress ectopic neuroma discharge.

Animal models of acute pain have consistently demonstrated the antinociceptive effect of tricyclic drugs. Controlled clinical trials of both tricyclics and SNRI antidepressants have shown beneficial results in postherpetic neuralgia, diabetic neuropathy, atypical facial pain and central pain. The NNT for effectiveness for antidepressants in neuropathic pain ranges from 2.9 for tricyclics to 5.8 for SNRIs. The effective dose of a tricyclic drug for analgesia is usually lower than that required for depression (although a dose response for analgesia has been demonstrated) and analgesia is apparent in 3–4 days compared with 3–4 weeks for antidepressant effects. Amitriptyline is the commonest tricyclic drug prescribed as an analgesic and the normal starting dose is 10–25 mg at night. Side-effects include sedation (which can be beneficial), constipation and a dry mouth. Other tricyclic drugs used as analgesics include imipramine and nortriptyline.

Selective serotonin reuptake inhibitors, such as fluoxetine, appear to be less effective analgesics.

Antiarrhythmic Drugs

Sodium channel blockers may be used to reduce pain caused by nerve damage. Both intraveneous lidocaine (up to 5 mg kg^–1) and oral mexiletine reduce neuropathic pain. Intravenous lidocaine appears effective in fibromyalgia (based on small patient numbers). Unfortunately, the benefits of lidocaine are short-lived and the studies are generally small.

Plasters containing 5% lignocaine have been recommended as another first-line drug for patients with postherpetic neuralgia or focal neuropathy with allodynia, based on three published positive trials. These plasters need to be applied daily for 12 h out of every 24 h.

Ketamine: Ketamine is an NMDA receptor antagonist which has been used successfully as an analgesic via intravenous, subcutaneous and oral routes. Psychometric side-effects may be a problem.

Capsaicin: Capsaicin is an alkaloid derived from chillies. It depletes substance P in local sensory nerve terminals. Local application may alleviate pain in painful diabetic peripheral neuropathy, osteoarthritis, postherpetic neuralgia, intercostobrachial neuralgia and psoriasis.

Recently, a capsaicin 8% plaster has been developed for use in treating neuropathic pain (except diabetic peripheral neuropathy). Although there is evidence of efficacy when used on a three-monthly basis, it is too early to say what its place will be in treating neuropathic pain.

Cannabinoids: Animal studies suggest that cannabinoids reduce hyperalgesia and allodynia in neuropathic, inflammatory and cancer pain. Human trials have also reported modest benefit in neuropathic pain. Cannabinoids act on CB₁ receptors, which are located in the brain, and their CB₂ counterparts found peripherally. Further research is needed to identify which cannabinoids may produce analgesia without psychotropic side-effects.

Oral Corticosteroids: The mechanism by which corticosteroids produce analgesia is unknown. They reduce inflammatory mediators, specifically prostaglandins. They reduce peritumour oedema, thus relieving pain by reducing pressure on adjacent pain-sensitive structures. They are administered for cerebral metastases, spinal cord compression, superior vena caval compression and neural infiltration or compression. In cancer patients, they are also prescribed for their euphoric effect and to stimulate appetite.

Interventional Pain Therapies

Therapeutic interventional therapies in the management of chronic and malignant pain have been performed for many years and include various types of nerve block and minimally invasive surgical procedures. There has been discussion and controversy regarding effectiveness, but significant progress has been made over the last two decades in establishing some evidence base for their use. Such techniques are often included as part of the multidisciplinary management of chronic pain.

Nerve blocks have been performed for many years in the management of pain. A nerve block comprises an injection of a local anaesthetic (sometimes combined with steroid) or a neurolytic agent around a peripheral or central sensory nerve, a sympathetic plexus or a trigger point. Correct use of interventional procedures in the treatment of chronic pain requires an experienced practitioner with a thorough knowledge of anatomy and an understanding of pain syndromes. Interventions should be undertaken in appropriate locations, usually day-case theatre suites, by clinicians who are fully acquainted with the techniques involved and who are competent to manage the complications which may arise. The use of radiological control and contrast media, ultrasound guidance or peripheral nerve stimulation is strongly advocated to confirm accurate needle placement.

Potential sites for neural blockade are shown in Figure 46.5, and indications for neural blockade are listed in Table 46.2. Some comments about commonly performed nerve blocks are made in the section below. For a full description of the techniques of neural blockade, the reader should consult suggested texts in the further reading section.

TABLE 46.2

Indications for Neural Blockade

Nerve Block	Indications
Trigger point injections	Myofascial pain, scar pain
Somatic nerve block	Nerve root pain, scar pain
Trigeminal nerve block and branches	Trigeminal neuralgia
Stellate ganglion block	SMP, CRPS
Coeliac plexus block	Intra-abdominal malignancy, especially pancreas
Superior hypogastric plexus block	Malignant pelvic pain
Lumbar sympathetic block	Ischaemic rest pain SMP, CRPS Phantom and stump pain
Epidural steroids/root canal injections	Nerve root pain, benign or malignant
Lumbar and cervical medial branch blocks	Back pain Whiplash cervical pain
Intrathecal neurolytics	Malignant pain
Percutaneous cervical cordotomy	Unilateral somatic malignant pain, short life expectancy

SMP, sympathetically maintained pain; CRPS, complex regional pain syndrome.

FIGURE 46.5 Potential sites for neural blockade.

Agents

Local Anaesthetics: Local anaesthetics block sodium channels and may be used for both diagnostic and therapeutic injections. They have been injected into muscle trigger points for the relief of myofascial pain and it has been shown that prolonged relief of pain may result sometimes from local anaesthetic blocks to peripheral nerves.

Corticosteroids: Corticosteroids have been shown to block transmission in normal unmyelinated C fibres and to suppress ectopic neural discharges in experimental neuromas. They are sometimes added to local anaesthetics in nerve blocks and for injection into painful scars.

Botulinum Toxin: Botulinum toxin has been used for the treatment of temporomandibular dysfunction, migraine and vulvodynia. No firm data on effectiveness is available.

Neurolytic Techniques

Neural destruction can be produced by chemical or thermal means. In general, the use of neurolytic techniques has diminished in the last two decades. There are many reasons for this, including the improved use of analgesic drugs, the recognition that the effect of neuroablative procedures is often transient, the development of neurostimulatory techniques and appreciation of the cognitive and behavioural elements of pain. The clinical indications for neurolytic techniques are now limited to patients with cancer pain and a few selected non-cancer conditions. Careful thought with regard to the potential benefits and risks of the procedure, appropriate patient selection and fully informed consent are essential before performing a neurolytic procedure.

Chemical Neurolysis: The commonest neurolytic agents used are phenol and ethyl alcohol. Phenol acts by coagulating proteins and destroys all types of nerves, both motor and sensory. It is available in water or in glycerol. Its most frequent indication is for lumbar sympathetic block for peripheral vascular disease. Large systemic doses cause convulsions followed by central nervous system depression and cardiovascular collapse. Alcohol is the neurolytic agent of choice for coeliac plexus block in patients with intractable abdominal pain due to pancreatic cancer, when the large volume required prohibits the use of phenol. It produces a higher incidence of neuritis than phenol and is not used for other blocks.

Radiofrequency Lesions: Radiofrequency lesioning is indicated for patients in whom non-invasive treatments have failed. A destructive heat lesion is produced by a radiofrequency current generated by a lesion generator. The radiofrequency electrode comprises an insulated needle with a small exposed tip. A high frequency alternating current flows from the electrode tip to the tissues, producing ionic agitation and a heating effect in tissue adjacent to the tip of the probe. The magnitude of this heating effect is monitored by a thermistor in the electrode tip. Damage to nerve fibres sufficient to block conduction occurs at temperatures above 45°C, although in practice most lesions are made with a probe tip temperature of 60–80°C. An integral nerve stimulator is used to ensure accurate positioning of the probe. Whereas the spread of neurolytic solutions is unpredictable, radiofrequency lesions are more precise. The size of the lesion depends on the tip temperature, the duration of the current and the length of the exposed needle tip. Lower-temperature lesions are now being used in an attempt to produce analgesia without nerve destruction in pulsed radiofrequency lesioning.

Radiofrequency lesions of the trigeminal nerve may be used to treat trigeminal neuralgia in the elderly patient whose pain is uncontrolled by anticonvulsant drugs and who is unsuitable for microvascular decompression. Radiofrequency lesions of spinal nerves, including the medial branch of the dorsal ramus, are used in some spinal conditions.

Epidural Steroids

Epidural steroids have been used since 1962 for nerve root pain. A recent meta-analysis of all randomized, controlled trials has concluded that epidural administration of corticosteroids is more effective in reducing lumbosacral radicular pain (in both the short and long term) than placebo. In addition, McQuay and Moore (1998) have addressed the question ‘How well do they work?’ by investigating the short-term (1–60 days) and long-term (12 weeks–1 year) efficacy of epidural steroids for sciatica. They used the NNT as a measure of clinical benefit. The NNT for short-term, greater than 75% pain relief was just under 7.3. The NNT for long-term (12 weeks–1 year) improvement was 13 for 50% pain relief.

The use of epidural steroids is not without potential hazards and controversy. The most common side-effects relate not to the steroid but to technical aspects of the technique. There have been reports of dural tap (2.5%), transient headache (2.3%) and transient increase in pain (1.9%). As with any spinal injection, an aseptic technique must be used and the usual contraindications observed. Methylprednisolone acetate and triamcinolone are the steroids most commonly used. It has been shown that neither of these preparations is deleterious when injected into the epidural space. However, they may have harmful effects if injected inadvertently into the subarachnoid or subdural spaces.

Before an epidural steroid injection is undertaken, the patient should receive a consultation during which the perceived merits, expectations, risks and possible complications are explained fully. This should include an explanation that the steroid preparation is being used outside its product licence. The doctor should be satisfied that the procedure is indicated, that appropriate neurological examination and investigations have been performed and that there is no contraindication to the procedure. Written consent should be obtained. Arrangements should be made for the outcome to be monitored formally by the doctor or team who prescribed the procedure or the one who performed it. Provision should be made for an earlier consultation if necessary.

Spinal Endoscopy

Spinal endoscopy is a minimally invasive procedure developed to enable the physician to visualize the epidural space and nerve roots. The epidural space can be accessed with a spinal endoscope and a steerable catheter via the sacral hiatus. This technique allows for a direct visual examination of a specific nerve root and any associated pathology. The catheter is used as a blunt dissector to lyse adhesions which encapsulate the affected nerve root. In addition, irrigation of the nerve root with saline may ‘wash away’ inflammatory mediators.

Nerve Root Injection

Local anaesthetics and steroids may be injected around a nerve root as it emerges from the intervertebral foramen. This is an alternative to an epidural steroid injection and may be useful when the level of nerve compression is demonstrated by an MR scan. X-ray screening is essential. This technique may be used in the cervical, thoracic and lumbar regions.

Medial Branch Block of the Dorsal Ramus (Lumbar and Cervical Facet Nerve Blocks)

Chronic back and neck pain are common complaints in pain management clinics. Lumbar and cervical facet joints are considered to be potential sources. Injections of local anaesthetic and steroid into both lumbar and cervical facet medial branch nerves are performed commonly, although there is controversy about long-term benefit. Radiofrequency lesions of the facet nerves have been reported to give long-term relief in appropriately selected patients.

Sympathetic Nerve Blocks

Visceral nociceptive afferents travel in the sympathetic nervous system to the spinal cord. Visceral pain tends to be less opioid-sensitive than somatic pain. Percutaneous sympathetic blocks may therefore be useful in the management of severe cancer-related visceral pain which is poorly controlled with opioids or controlled only with intolerable side-effects.

Percutaneous coeliac plexus block using 50% alcohol is one of the most commonly used and effective blocks performed for cancer pain. It is used for pain resulting from upper gastrointestinal neoplasms, in particular carcinoma of the pancreas. Radiological screening, either X-ray or CT, is mandatory, although this does not ensure absence of complications. Hypotension, especially postural hypotension, should be anticipated and managed appropriately. Serious complications are rare, but include paraplegia.

The superior hypogastric plexus innervates the pelvic viscera. Superior hypogastric plexus block with phenol has been used for pelvic pain from cervical, prostatic, colonic, rectal, bladder, uterine and ovarian malignancy, and rectal tenesmus.

Chemical lumbar sympathectomy using phenol is performed for inoperable ischaemic leg pain. Radiological screening using contrast medium is necessary to ensure correct positioning of the needle. The complication rate is low, the most common complication being genitofemoral neuralgia, with a reported incidence varying from 4% to 15%.

Stellate ganglion and lumbar sympathetic block with local anaesthetic are sometimes helpful in the treatment of sympathetically mediated pain, CRPS types I and II, amputation stump and phantom pain.

Intravenous Regional Sympathetic Block with Guanethidine

The intravenous regional guanethidine technique was reported in 1974 and it became a popular method of treating CRPS. The technique is the same as intravenous regional analgesia (IVRA), but with the addition of guanethidine 10–20 mg. However, a recent systematic review of the randomized, controlled studies of intravenous regional guanethidine block in the treatment of CRPS failed to show evidence of effectiveness.

Stimulation-Induced Analgesia

Transcutaneous electrical nerve stimulation, spinal cord stimulation, deep brain stimulation and acupuncture may produce stimulation-induced analgesia.

Transcutaneous Electrical Nerve Stimulation

Transcutaneous electrical nerve stimulation (TENS) has been used widely since Melzack and Wall proposed the gate control theory in 1965. They postulated that large-diameter primary afferents exert a specific inhibitory effect on dorsal horn nociceptive neurones and that stimulation of these fibres would alleviate pain. Conventional TENS produces high-frequency, low-intensity stimulation which relieves pain in the area in which it produces paraesthesia. Stimulation variables of TENS may be altered to produce low-frequency acupuncture-like TENS, which, unlike conventional TENS, produces analgesia which is antagonized by naloxone.

A small battery-powered unit is used to apply the electrical stimulus to the skin via electrodes (Fig. 46.6). These are placed over the painful area, on either side of it or over nerves supplying the region, and stimulation is applied at an intensity which the patient finds comfortable. Adverse effects are minimal, with allergy to the electrodes being the commonest problem encountered. TENS is used for a variety of musculoskeletal pains and has been advocated recently for refractory angina. Tolerance to TENS does occur sometimes. It may be possible to overcome this by changing stimulation variables.