Pain Management 385

Pain Management
A R Molloy and M J Cousins, University of Sydney, Sydney, NSW, Australia
Crown Copyright 2009 Published by Elsevier Ltd. All rights reserved.

Introduction
Advances in neuroscience and psychology over the past 30 years have revolutionized our understanding of the reasons for the variability and complexity of pain and have provided new evidence-based treatment options. Pain is now viewed as a complex perception associated with an array of interactions at the level of the peripheral and central nervous systems, involving sensory, emotional, cognitive, and environmental factors. Instead of treating pain report in isolation, there is a range of treatment options available to the multidisciplinary pain management team, targeting relevant outcomes such as function, mood, quality of life, acceptance of pain, and optimal adjustment to persisting pain. A number of key events in the evolution of pain management as a specialty should be noted. The establishment of the first multidisciplinary pain clinic in Seattle at The University of Washington in 1960 by Professor John Bonica led to widespread recognition of this approach. The publication of the gate control theory of pain in 1965 by Melzack and Wall was significant for two reasons: it recognized the role of the spinal cord in modulation of signals from both nociceptors in the periphery and descending pathways and highlighted the potential role of psychological factors in activating descending pain-inhibitory pathways. Since the establishment of the International Association for the Study of Pain in 1974, this organization has attracted over 6000 members from a range of disciplines in more than 80 countries. Chronic pain has been described as the hidden epidemic affecting one in five adults, up to 80% of patients with advanced cancer, and in AIDS the estimated prevalence is 3080%. Based on the wealth of scientific research available, it has been proposed that persistent pain is a disease entity and warrants the same health focus as other major diseases such as diabetes and cancer. Linked to this is the call to recognize evidence-based treatment of pain as a basic human right, as studies consistently show that pain is often undertreated even when resources are available.

silent nociceptors, are only activated by noxious stimuli in the presence of tissue damage. Nociceptors convert a range of noxious environmental stimuli (thermal, mechanical, and chemical) into action potentials that reflect the intensity and duration of the insult. The effect on nociceptors is mediated through a wide range of inflammatory mediators, including ATP, bradykinin, prostinoids, serotonin, histamine, and hydrogen ions (tissue acidosis). Nociception is not pain, as pain can only be experienced by the conscious brain. Diagnosis is usually straightforward in acute pain, as there is usually broad concordance between symptoms, physical signs, and pathology; however, there is no direct relationship between the amount of tissue injury and pain. Acute pain is typically dull and aching and anatomically related to the area of pathology. Acute pain usually resolves in a predictable period once the noxious stimulus is removed and normal healing progresses. Multimodal analgesic and interventional techniques which target different mechanisms contributing to the pain are recommended for moderate to severe pain to reduce side effects associated with individual drugs, in particular opioids. Options include drugs such as nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, ketamine, gabapentin, wound infiltration, regional local anesthetic blocks and spinal opioid administration. Uncontrolled acute pain should rarely be a clinical problem except in special cases, such as the patient with previous trauma to the tissues (e.g., surgery or injury), incomplete healing, persistent inflammation, or nerve injury (either peripheral or central), and those on large doses of opioid medication, or if there is a history of substance abuse. In these cases factors such as peripheral and central sensitization and tolerance may either singly or in tandem result in the heightened experience of pain, and nonstandard analgesic regimes such as a subcutaneous or systemic infusion of ketamine and lignocaine (singly or in combination) may be required.

Chronic or Persistent Pain

Chronic or persistent pain refers to the pain that a significant proportion of patients will continue to experience despite appropriate medical or surgical assessment and intervention. For epidemiological purposes a period of 3 months is taken, but in practical terms chronic pain may be present as early as 2 weeks. Epidemiological studies in different countries are remarkably consistent. Approximately 20% of the population will experience persisting pain, with about half of those patients distressed and disabled.

Acute Pain
Everyday acute pain is associated with stimulation of nociceptors, which are peripheral sensory receptors on Ad and C-fibers. Other Ad and C-fibers, called

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There are three main categories of factors contributing to chronic pain: nociceptive, neuropathic, and psychological/environmental. Nociceptive pain refers to the pain associated with ongoing tissue damage that can last long after the initial noxious stimulus. Components of this type of pain are involved in the pain of osteoarthritis, rheumatoid arthritis, unhealed fractures, and chronic infections. A different clinical presentation is associated with neuropathic pain, which is due to damage, disease, or section of the peripheral or central nervous system. Pain descriptors include a range of dysesthetic sensations such as burning, shooting, or electric shocks. The topographical distribution of neuropathic pain tends to be regional rather than dermatomal. For example, in a variant of neuropathic pain, complex regional pain syndrome (CRPS), the dysesthetic pain may occupy the whole of the upper limb following a trivial injury to the hand. Common associated phenomena are allodynia (pain experienced after a nonpainful stimulus e.g., touching sunburned skin), hyperalgesia (severe pain experienced after a mildly painful stimulus), abnormal motor responses, and disturbance of sympathetic activity such as sweating, swelling, and color change. In the case of persistent

low back pain, there may be neuropathic, nociceptive, and psychosocial components contributing to the pain experience. In many cases there will be no evidence of nerve or tissue damage for example, in CRPS type 1, where ongoing pain is considered to be due to dysfunction of part of the nervous system. Neuropathic components of pain may be classified according to the etiology of the pain, the anatomical site, or a mechanism-based classification. Such systems have been of variable utility clinically, as it is likely that multiple pain mechanisms are operating simultaneously. Also, as plasticity is an inherent feature of animal and human sensory pathways, neuronal systems involved in the experience of pain may alter over time. The biomedical model is generally inadequate in cases of persisting pain. The biopsychosocial model proposed by Engel has been widely accepted, as it provides a better analysis of all of the factors contributing to persistent pain. Figure 1 shows the typical factors that inadvertently cause an increase in suffering. The biopsychosocial model requires that the bio(medical), psycho- (psychological), and social (environmental) factors are assessed so that all treatable

Reduced activity

Physical deterioration (e.g., muscle wasting, joint stiffness)

Unhelpful beliefs and thoughts Chronic pain Feelings of depression, helplessness, irritability Excessive suffering

Repeated treatment failures

Long-term use of analgesic, sedative drugs

Side effects (e.g., stomach problems lethargy, constipation)

Loss of job, financial difficulties, family stress

Figure 1 When chronic pain becomes a problem. Reproduced with permission from MK Nicholas, Pain Management and Research Centre, Royal North Shore Hospital, St. Leonards, NSW, Australia.

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factors are identified. A diagnostic formulation and treatment plan are then arrived at after a round table interdisciplinary meeting. A diagnosis may result from the medical assessment, but a formulation looks at the impact of the patients pain and possible modulating factors. The importance of a formulation lies in the fact that a patient may have the same diagnosis, but the impact in terms of mood, function, and quality of life may be very different. An important concept is that persistent, physical pain changes the nervous system, and adverse psychological/environmental adaptations become self-sustaining; this process represents a disease entity. Patients with persisting pain should be referred to a pain center as early as possible. Figure 2 is a suggested algorithm.

vary from a percutaneous intrathecal or epidural catheter to an implantable programmable pump. Outcome studies have shown that intrathecal morphine administration is associated with improved pain control, reduced side effects, less use of adjuvant pain medications, and improved survival in a cancer pain population, as compared to standard medical management.

Pharmacological Treatments
The application of evidence-based medicine, the introduction of novel analgesic agents, and the publication of a range of guidelines (e.g., Oxford League Tables) have resulted in a more rational approach to prescribing. A commonly used tool to describe analgesic efficacy is numbers needed to treat (NNT). This is defined as the number of patients who need to receive an analgesic, for one patient to report a predetermined level of pain relief (usually 50%) more than the placebo group. While being a useful tool, few studies provide a cohort of the more than 500 patients needed to calculate a credible NNT. An analgesic with high efficacy has an NNT of 23. The flip side is that these measures are not only drug, dose, and context specific but also do not reflect minor and major adverse events (expressed as numbers needed to harm (NNH)).
Acetaminophen

Cancer Pain
Pain is experienced by approximately 6080% of patients with advanced cancer. Nociceptive and neuropathic components of pain occur either singly or in combination, as in chronic pain. However, the underlying disease process is usually progressive, resulting in the need for regular reviews and adjustments of the analgesic regime. Analgesic titration is further compounded by drug interactions with other therapeutic agents and by symptoms such as fatigue, constipation, dyspnea, and impaired cognitions. By tailoring multimodal analgesic drug therapy to each patients needs, at least 85% of patients should experience effective pain relief. Other options include chemotherapy and radiotherapy, which are also associated with pain relief by reducing tumor bulk. Biphosphonates produce morphological change and apoptosis of osteoclasts which are responsible for osteoclast-induced skeletal metastases. Pinning or surgical treatment of fractures may be required, as up to 30% of patients with bony metastases develop long bone fractures. Breakthrough pain is a heterogeneous group of complaints related to spontaneous neuropathic components, incident pain associated with movement, and pain secondary to fluctuations in analgesic levels. Distinction between these causes is important, as treatment will be different. For incident pains such as associated with dressing changes, a preemptive dose of an opioid, such as immediate-relief morphine, should be taken. Approximately 10% of patients do not experience adequate pain relief. Therapeutic options must take account of prognosis, location of pain, type of pain, coexistent disease, and psychosocial factors. Traditionally neurolytic blocks were favored but increasingly spinal drug administration is used, which may

Acetaminophen is one of the most commonly used analgesics worldwide. This drug is available as an oral, rectal, and intravenous preparation. Its mode of action remains undefined. Hypothesis suggest an action on a number of systems, including inhibition of central cyclooxygenases COX-2 and COX-3, modulation of descending serotoninergic pathways, action on the N-methyl-D-aspartate (NMDA) receptor, or an action related to nitric oxide. The evidence for the clinical efficacy of acetaminophen is good and it is usually recommended as a first-line analgesic in mild to moderate acute and cancer pain, and as part of a multimodal approach in severe pain. It is regularly combined with other analgesics, such as codeine. It is well tolerated and side effects are rare, except for liver failure associated with an overdose.
NSAIDs

The introduction of a number of selective COX-2 inhibitors (coxibs), in addition to aspirin and the traditional nonselective (COX-1 and COX-2) NSAIDs, has provided a range of new treatment options but has also highlighted a number of concerns over this drug class. All NSAIDs have analgesic, anti-inflammatory,

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Patient reporting pain persisting and seeking help with it Cause known Cause unknown, but serious causes excluded Cause unknown Further investigations, specialist review Treat accordingly or

No curative treatment available and Pain relief measures not helping and/or Pain interfering in daily activities and/or mood state Consider Referral to pain clinic for multidisciplinary assessment At pain clinic

Assessment of medical, psychological and social/environmental aspects of case Team meeting to review findings of assessments, history and previous reports Develop formulation of case, identifying problems and contributing factors Develop management plan: Identify goals (e.g., pain relief, functional tasks, improve mood, medication/treatment change) Intervention options (aimed at achieving goals; plan whether in sequence or combinations): Further investigations/tests Education/reassurance Medication (optimise/rationalise) Liaison with GP (advice/support) Nerve blocks/implanted devices Individual psychological/psychiatric or physiotherapy treatment Group-based multidisciplinary pain management program Follow-up/review: Assess implementation of plan (deal with shortcomings, new revelations) Evaluate outcomes (consider need for further investigations/treatments) Maintenance plan (coordinate with GP, other specialists or agencies) Ongoing-management of persisting pain using active +/ passive strategies and GP support as needed
Figure 2 Algorithm: who and when to refer to a pain clinic. Adapted from Nicholas MK (2004) When to refer to a pain clinic. Best Practice & Research Clinical Rheumatology 18(4): 613629.

and antipyretic actions which result from their action in reducing prostaglandin concentrations both peripherally and centrally. The mechanism of action also explains the range of adverse events witnessed clinically. The principal COX-1 side effects are

gastrointestinal (GI) ulceration and bleeding (COX-1 is involved in the production of prostaglandin E2 and prostacyclin, which have a protective action on the gastric mucosa) and a platelet-inhibiting effect (COX-1 has a role in the production of thromboxane A). The latter

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side effect is used therapeutically to reduce platelet aggregation and the risk of stroke and myocardial infarction. Coxibs have the same clinical efficacy as do traditional NSAIDs but are associated with significantly reduced risk of GI complications, although the same renal precautions apply. While they do not interfere with the action of thromboxane A in platelets, the inhibition of prostacyclin in the endothelium may explain the high incidence of thrombogenic adverse events observed with rofecoxib that led to the withdrawal of this drug worldwide. This raised the question as to whether this was a class effect of coxibs. Rofecoxib (methyl sulfone) has a chemical structure different from that of the other coxibs (arysulfonamides), which may explain the clinical differences. Coxibs are still represented in the market by celecoxib (oral preparation) and parecoxib (intravenous administration).
Antidepressants, Systemic Local Anesthetics, and Anticonvulsants

of their established role in epilepsy but now they are considered as specific analgesics for chronic pain; also more recently a role in acute pain has been identified. Their main action is to differentially suppress spontaneous ectopic neuronal activity at drug concentrations that do not block normal neuronal conduction (approximately 3 times less). In broad terms this effect may be achieved either by drugs such as carbamazepine, lamotrigine, mexiletine, and lignocaine, which block sodium channels, or gabapentin and pregabalin, which also bind to the a2d subunit of the voltage-gated calcium channel. A variety of side effects have been reported, ranging from lightheadedness and dizziness to ataxia, severe skin rashes (lamotrigine), and arrhythmias (mexiletine).
Opioids

The increasing evidence base showing improved pain control with tolerable side effects has resulted in the antidepressant, systemic local anesthetic, and anticonvulsant groups of drugs being accepted as specific analgesics for neuropathic pain. Most studies have been in painful diabetic neuropathy (PDN) and postherpetic neuralgia (PHN), as these are common neuropathic pain conditions. Use of these drug classes for other neuropathic pain syndromes is on the presumption that similar neurobiological processes are involved, although it is almost certain that a number of mechanisms underlie the majority of neuropathic pain syndromes and that more than one drug may be required. At present there are no widely accepted drug administration algorithms for neuropathic pain and few studies comparing one drug with another or the outcomes associated with multiple drug use. While almost all studies with tricyclic antidepressants (TCAs) have shown that their use is associated with pain relief, their clinical use is limited by the frequency of associated side effects, which includes dry mouth, constipation, blurred vision, urinary hesitancy, and postural hypotension. This has led to studies on the newer antidepressants, which have a more favorable side effect profile. These include the selective serotonin reuptake inhibitors (SSRIs) and those that inhibit the uptake of both serotonin and noradrenaline (SNRIs). To date the results have not been clear-cut but more evidence is accumulating to support their use. Anticonvulsants and systemic local anesthetics are drugs which have the ability to suppress ectopic neuronal activity. Initially their use was an extension

Opioids are the mainstay of management of moderate to severe acute pain. In most cases the opioid acts through the m receptor, which is similar among species, permitting extrapolation from animal studies. Attempts to clinically target the d receptor, k receptor, and opioid-like receptor (ORL1) have been largely unsuccessful. Although morphine has been the traditional firstline drug, there is now a range of opioids available with differing pharmacokinetics and pharmacodynamics. These include fentanyl, codeine, meperidine, oxycodone, hydromorphone, buprenorphine, and methadone. Fentanyl is a synthetic opioid which is up to 100 times more potent than morphine and has rapid onset and offset due to high lipid solubility. Codeine may be administered orally or intramuscularly or in tablet form combined with paracetamol or an NSAID. Meperidine is a synthetic opioid that has a short half-life and is being used less due to problems with addiction and the risk of convulsions with normeperidine, the major metabolite. Oxycodone and hydromorphone are useful alternatives to morphine. Hydromorphone has approximately seven times the potency when given spinally. Methadone is a synthetic opioid with a long and variable half-life. It has been used increasingly in chronic pain management due to an action on the NMDA receptor. The usual routes of administration are oral or parenteral (subcutaneous, intramuscular, or intravenous). As there is a wide variation in opioid requirements, patient-controlled analgesia (PCA) devices are often used postoperatively to allow patients to titrate opioid doses to their needs. Increasingly the benefits of epidural and intrathecal opioid administration are being recognized. Side effects of opioids include respiratory depression, nausea, vomiting, endocrine abnormalities, and bowel dysfunction, in particular constipation.

390 Pain Management Ziconotide

This peptide is a selective for the N-type calcium channel and is approved by the US Food and Drug Administration (FDA) for intractable pain in those for whom intrathecal infusion is appropriate and who have failed to respond to more conservative measures and intrathecal morphine. This drug has a narrow therapeutic index with side effects such as dizziness, nystagmus, confusion, gait disturbance, and urinary retention.
Ketamine

problems such as fentanyl patches in short bowel syndrome, to target specific sites (e.g., topical lignocaine patches in postherpetic neuralgia), or to access specific analgesic receptors, such as peripheral or spinal opioid receptors. Low-dose buprenorphine patches, changed every 7 days, provide long-duration, well-tolerated analgesia, particularly in the older age group.

Invasive Treatments
Peripheral Nerve Stimulation

Glutamate acting through the NMDA receptor in the dorsal horn is associated with amplification and prolongation of nociceptive input, termed wind-up. Central hypersensitivity that results is implicated in persistent pain states. NMDA receptor antagonists, including ketamine, dextrometorphan, and memantine, have been successful in treating clinical pain conditions with significant components of hyperalgesia and allodynia. Ketamine is the most widely used drug in this group and has been used orally, subcutaneously, and intrathecally. Because of actions at other NMDA receptors, particularly in the CNS, side effects are common and include somnolence and dysphoria. Although it has been used intrathecally, concerns have been raised about neurotoxicity.
a2 Agonists

The technique of peripheral nerve stimulation, which is thought to activate large, low-threshold afferent fibers, may be considered when persistent pain is well localized and lead placement in the region of the pain is technically feasible. Drawbacks are that the leads may displace or break. An increasingly common indication is headache due to occipital neuralgia, postherniorraphy nerve pain, and other types of postoperative neuropathic pain. This technique should be avoided where there is a significant central component to the pain.
Spinal Cord Stimulation

Clinical efficacy has been demonstrated for a2 agonists given spinally in nociceptive and neuropathic pain. Although used orally and topically, clonidine is most commonly administered intrathecally, usually in combination with an opioid. Side effects include sedation and hypotension.
Methods of Drug Delivery

Studies have shown that the delivery of both established and new drugs by modern drug delivery devices and novel routes of administration are often associated with improved analgesic outcomes. In a particular patient, contemporary multimodal acute pain management may involve many routes, such as oral, intravenous, and intraspinal drug administration. Although in persistent pain management there is a greater focus on contributing psychosocial aspects, it is important to minimize side effects associated with analgesic therapy so that function can be promoted. Oral administration is recommended if bowel function is normal, or parenteral (subcutaneous, intramuscular, or intravenous) if it is impaired, such as postoperatively. Other routes are generally indicated to shorten the onset of action (e.g., transmucosal or nasal fentanyl), to address concurrent medical

Highly sophisticated systems are now available to electrically stimulate parts of the spinal cord and brain. The proposed mechanism of action of spinal cord stimulation (SCS) is a combined activation of descending inhibitory pathways and release of a cascade of neuroactive substances in the region of stimulation, particularly g-aminobutyric acid (GABA). Nociceptive pain is poorly responsive to SCS, but conditions such as neuropathic pain, ischemic limb, cardiac pain, and CRPS are accepted indications. There is a significant incidence of complications, in particular infection, lead breakage, and electrode movement.
Deep Brain and Motor Cortex Stimulation

Deep brain stimulation and motor cortex stimulation have been used for pain that has been unresponsive to all other therapeutic modalities. Deep brain stimulation usually involves stimulation of the sensory thalamic nuclei, which target neuropathic pain, and the periacqueductal gray, which is effective for certain types of nociceptive pain. Motor cortex stimulation shows promise for severe central pain.
Intraspinal Drug Delivery

Modification of spinal function by epidural and intrathecal drug administration depends on administration of either local anesthetics which block neuronal sodium channels in spinal nerve roots or drugs which

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act at a spinal cord dorsal horn level on other receptor systems (e.g., opioid receptors). Local anesthetics have a rapid onset, as they block nerve roots which pass through the epidural or intrathecal space. Drugs targeting spinal cord m or GABA sites have a slower onset, as they need to target receptors on primary afferent endings or at supraspinal sites. Epidurals are widely used for the management of labor pain and postoperative pain management, particularly in patients with potential respiratory compromise. Larger volumes of local anesthetic are required to achieve sensory blockade as compared to intrathecal analgesia. Spinal drug administration also has an established role in both chronic noncancer and cancer pain. Up to 10% of patients experience severe cancer-related pain despite optimal medical management. Many patients with nonmalignant pain also fail to report benefit with oral or parenteral medication or experience unacceptable side effects. Intraspinal drug delivery should be considered in these patients, as a range of spinal and supraspinal receptors can be targeted which may be associated with improved analgesia and a reduction in side effects associated with systemic administration. Delivery may be epidural, intrathecal, or intracerebroventricular through either an externalized system or a fully implanted system. Currently a range of battery-powered or gas-driven implantable infusion systems are available and also a complementary hand-held device with the facility to deliver bolus doses as needed. Equivalent analgesia may be obtained with epidural administration at one-tenth of the parenteral morphine dose and intrathecally at one-tenth of the epidural dose. Intraventricular, compared to intrathecal, administration requires smaller doses. Although currently at least 16 drugs have been used intrathecally, only morphine sulfate, ziconitide, and baclofen have been approved by the US FDA for intrathecal use. There is concern over the long-term safety of many of the other compounds and drug mixtures used. Spinal drug administration may be associated with a different spectrum of side effects. For example, intrathecal morphine may be associated with the growth of catheter tip inflammatory masses. Outcome studies have shown that intrathecal morphine administration is associated with improved pain control, reduced side effects, less use of adjuvant pain medications, and improved survival in a cancer pain population as compared to standard medical management. This approach can also be of benefit in carefully selected patients with severe and disabling chronic nonmalignant pain. Combination of these approaches with an intensive cognitive behavioral pain program may produce a better outcome than either treatment alone.

Neurodestructive

Although neurodestructive techniques are used in certain chronic noncancer conditions such as trigeminal neuralgia and spinal medial branch rhizotomy, they are to be avoided in most other cases due to the high incidence of deafferentation pain. Neurolytic procedures using phenol or alcohol, which permanently interfere with the function of nerves, are usually reserved for well-localized cancer-related pain, in patients with a short life expectancy. Common clinical examples include celiac plexus block for pancreatic cancer, and subarachnoid neurolytic blocks for pelvic pain and for unilateral chest wall pain associated with mesothelioma.
Radiofrequency

Radiofrequency techniques have been used for over 25 years to interrupt nerve transmission at various anatomical points. Most commonly the medial branch of the posterior primary division supplying the affected spinal segment (sacral, lumbar, thoracic, or cervical) is targeted after selection on the basis of concordant relief, with injection of one or more different local anesthetics or saline onto the medial branch or into the facet joint. Up to 80% of patients experience initial relief, with a variable period of sustained benefit from weeks to over 1 year. The dorsal root ganglion, the cervical spinothalamic tract in the treatment of cancer pain (known as a cordotomy), and the lumbar sympathetic chain are also potential targets for this technique. The role for these techniques is not clear, but they are relatively simple and well tolerated.

Treatment of Psychological and Environmental Factors

Psychosocial Assessment and Management of Pain

Psychosocial assessment, which includes assessment of psychological and environmental factors, is widely accepted as an essential part of the evaluation of persisting pain conditions. The assessment aims to identify the main presenting problems and the contributing somatic, psychosocial, and demographic factors. A formulation of relevant domains is then presented at a multidisciplinary conference and targets are identified for intervention. Typically a series of validated self-report questionnaires covering the relevant domains such as mood, function, coping strategies, pain behaviors, self-efficacy, and tendency to catastrophize are also completed by the patient. These can also be completed after treatment and should give a reliable indication of change and act as a check on patients verbal reports.

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Interventions can be delivered either serially (over weeks or months), as part of an intensive pain program, or as a component of a coordinated management plan (e.g., spinal cord stimulation and pain program). As these treatments are aimed at helping the patient to live with their pain, it is recommended that all medical and surgical treatments targeting pain relief are completed before commencing the program. Most evidence is for multidisciplinary treatments that are delivered according to cognitive behavioral principles, whereby patients learn a set of active pain management skills, which replace other unhelpful strategies. Treatments have to be tailored to the individuals needs and also integrated with the workplace if return to work is a goal. In general terms there is a dose-related response such that the more disabled patients do better with more intensive treatment. Significant improvements in pain, mood, function, and quality of life have been shown. Inevitably some patients do not benefit from this approach. Possible reasons are inadvertent reinforcement of passivity, lack of acceptance of persisting pain, poor patient compliance, and conflicting treatment advice. Such patients may seek further treatments targeting pain reduction after a pain program, and the risk is that further passive approaches will be introduced, reinforcing disability. In such cases individual sessions with a clinical psychologist may be appropriate.
See also: Deep Brain Stimulation; Neuropathic Pain; Neuropeptides: Pain; Nociceptor Responses; Pain Pathways: Descending Modulation; Pain and Genes; Pain: Central; Pain: Neuroimaging; Spinal Cord Pain Systems; Synaptic Transmission: Models.

Cousins MJ, Brennan F, and Carr DB (2004) Pain relief: A universal human right. Pain 112(12): 14. Cousins MJ and Bridenbaugh PO (eds.) (1998) Neural Blockade in Clinical Anesthesia and Management of Pain, 3rd edn. Philadelphia: Lippincott-Raven. Dolin SJ, Cashman JN, and Bland JM (2002) Effectiveness of acute postoperative pain management. Evidence from published data. British Journal of Anaesthesia 89: 409423. Flor H, Kalso E, and Dostrovsky J (eds.) (2006) Proceedings of the 11th World Congress on Pain. Seattle: IASP Press. Hassenbusch SJ, Portenoy RK, Cousins M, et al. (2004) Polyanalgesic Consensus Conference 2003: An update on the management of pain by intraspinal drug delivery Report of an expert panel. Journal of Pain Symptom Management 27(6): 540563. Loeser JD (ed.) (2001) Bonicas Management of Pain, 3rd edn. Philadelphia: Lippincott, Williams & Wilkins. McMahon S and Koltzenberg M (eds.) (2005) Wall and Melzacks Textbook of Pain, 5th edn. London: Elsevier Science. Moore A, Edwards J, Barden J, et al. (eds.) (2003) Bandoliers Little Book of Pain. Oxford: Oxford University Press. Morley S, Eccleston C, and Williams A (1999) Systematic review and meta-analysis of randomised controlled trials of cognitive behaviour therapy and behaviour therapy for chronic pain in adults, excluding headache. Pain 80: 113. Nicholas M, Molloy A, Tonkin L, et al. (2001) Manage Your Pain. Sydney: ABC Books. Nicholas MK (2004) When to refer to a pain clinic. Best Practice & Research Clinical Rheumatology 18(4): 613629. Siddall PJ and Cousins MJ (2004) Persistent pain as a disease entity: Implications for clinical management. Anesthesia & Analgesia 99(2): 510520.

Relevant Websites
http://www.anzca.edu.au Australian and New Zealand College of Anaestheticists: Acute Pain Management: Scientific Evidence. http://www.iasp-pain.org International Association for the Study of Pain. http://www.kovacs.org Kovacs Foundation, European guidelines for prevention of low back pain. http://www.kovacs.org Kovacs Foundation, European guidelines for the management of chronic nonspecific low back pain. http://www.mskcc.org Memorial Sloan-Kettering Cancer Center. http://www.pmri.med.usyd.edu.au Pain Management Research Institute, Royal North Shore Hospital, University of Sydney.

Further Reading
Australian and New Zealand College of Anaesthetists and Faculty of Pain, Medicine (2005) Acute Pain Management: Scientific Evidence, 2nd edn. Melbourne: ANZCA.