Why Should We Aim to Optimise the Management of Acute Pain?

Post-operative pain is a major marker of peri-operative morbidity and mortality and its effective treatment should be a goal in every hospital and institution. We should all aim to control pain, not only for humanitarian reasons, but also to attenuate the psychological and physiological stress with which it is associated following trauma or surgery. While it is now recognised that adequate pain control alone is not sufficient to reduce surgical morbidity, it remains an important variable and one that is perhaps more readily controlled (Kehlet and Holte 2001).

Adequate management of post-operative pain is vital to attenuate the stress response to surgery and the accompanying pathophysiological changes in metabolism, respiratory, cardiac, sympathetic nervous system and neuro-endocrine functions. These effects (summarised in Neuroendocrine and metabolic responses to surgery after NH&MRC 1999) are wide ranging and have significant impact on homeostasis. Effects on the respiratory system are most prominent, as persistent pain will result in a reduction in respiratory effort that then leads to hypoxaemia from significant ventilation / perfusion mismatching. Continuing hypoventilation predisposes to collapse of lung segments and the supervening infection that follows carries significant morbidity. Psychological and behavioural changes (e.g. yellow flags) also accompany pain states and may need to be recognised and managed. Not only will proper management of post-operative pain result in greater patient comfort and earlier discharge home, but the improved earlier mobilisation and return to function will also reduce serious post-operative complications such as venous thromboembolism.

Neuroendocrine and Metabolic Responses to Surgery (after NH & MRC 1999)

Endocrine

  • Catabolic – Due to increase in ACTH, cortisol, ADH, GH, catecholamines, renin, angiotensin II, aldosterone, glucagon, interleukin-1

  • Anabolic – Due to decrease in insulin, testosterone

Metabolic

  • Carbohydrate – hyperglycaemia, glucose intolerance, insulin resistance

  • Due to increase in hepatic glycogenolysis (epinephrine, glucagon) –gluconeogenesis (cortisol, glucagon, growth hormone, epinephrine, free fatty acids)

  • Due to decrease in insulin secretion / action

  • Protein – muscle protein catabolism, increased synthesis of acute-phase proteins

  • Due to increase in cortisol, epinephrine, glucagon, interleukin-1

  • Fat – increased lipolysis and oxidation

  • Due to increase in catecholamines, cortisol, glucagon, growth hormone

  • Water and electrolyte flux – retention of H2O and Na+, increased excretion of K+, decreased functional extracellular fluid with shifts to intracellular compartments

  • Due to increase in catecholamines, aldosterone, ADH, cortisol, angiotensin II, prostaglandins and other factors

However, despite the emergence of pain management as a specialty and the availability of a wide range of guidelines and templates for effective analgesia, pain continues to be poorly managed. Why this should be the case is a difficult question to answer, although there is clearly a wide range of possibilities (Cousins and Phillips 1986; Macintyre and Ready 1996).

As can be seen from “Reasons for ineffective analgesia (after NH&MRC 1999)”, in some cases it may be simply the result of inadequate knowledge or equipment, but sometimes there can be more disturbing reasons. Macintyre (2001) has pointed out that some health service personnel are still concerned that pain relief can be ‘too efficacious’ and thereby mask post-operative complications such as urinary retention, compartment syndrome or even myocardial infarction. Another barrier to providing effective analgesia is a view held in some quarters that maintaining the patient in pain is somehow a useful way to aid diagnosis –a concept that with no valid scientific basis (Attard et al. 1992; Zolte and Cust 1986).

Reasons for Ineffective Analgesia (After NH & MRC 1999)

  • The common idea that pain is merely a symptom and not harmful in itself

  • The mistaken impression that analgesia makes accurate diagnosis difficult or impossible

  • Fear of the potential for addiction to opioids

  • Concerns about respiratory depression and other opioid related side effects such as

  • nausea and vomiting

  • Lack of understanding of the pharmacokinetics of various agents

  • Lack of appreciation of variability in analgesic response to opioids

  • Prescriptions for opioids, which include the use of inappropriate doses and / or dose intervals.

  • Misinterpretation of doctor’s orders by nursing staff, including use of lower ranges of opioid doses and delaying opioid administration

  • The mistaken belief that patient weight is the best predictor of opioid requirement

  • The mistaken belief that opioids must not be given more often than 4 hourly

  • Patients’ difficulties in communicating their need for analgesia

Mechanisms in Acute Pain

The manner in which pain signals are processed and modulated is a complex topic that is covered in detail elsewhere. However the following brief overview is provided as a background to the sections that follow.

The traditional view of the processing of pain inputs is that they are first detected through non-specific polymodal nociceptors that respond to a range of stimuli, including thermal, chemical and mechanical alterations. It is a process designed to alert us to tissue damage. These inputs are then transmitted by A delta and C type fibres to the spinal cord at speeds of between 2 m / s in the case of the C type fibres and 10 m / s in the myelinated A delta fibres.

These peripheral nerves terminate in the dorsal horn of the spinal cord where they undergo considerable modulation both via neurotransmitters present at that site and through the action of descending tracts from higher centres, which usually have an inhibitory role. Following modulation, the nociceptive impulse is finally transmitted through tracts to supraspinal sites. Although a number of links are involved, the spinothalamic tract is perhaps the most prominent.

Having given this outline, it is now accepted that our nervous system is a “plastic” environment where stimuli or trauma in any one part of the body can invoke change within other body systems, especially that of the nervous system (Cousins and Power 1999). Changes in nerve function are particularly important and this plasticity can lead nerve fibres whose physiological role is not normally to transmit pain signals to act as nociceptors. For example, while A delta and C fibres are traditionally seen as primary nociceptive fibres, A beta fibres can become nociceptive under certain circumstances.

Coincident with this is the development of peripheral sensitisation. Trauma or other noxious stimuli to tissue results in a neurogenic inflammatory response that in turn leads to vasodilation, increased nerve excitability and the eventual release of a range of inflammatory mediators such as serotonin, substance P, histamine and cytokines –the so called sensitising soup. This altered environment leads to a modification in the way that input signals are processed with innocuous stimuli being sensed as noxious or painful stimuli, leading to the phenomena of hyperalgesia.

The Scope of Acute Pain Management

Acute pain management has developed into a sub-specialty in its own right during the last decade with an ever-increasing range of activities. In the hospital setting, the major role of the acute pain team is in the area of post-operative pain management in the surgical patient, although their involvement must not be limited to these patients. In patients with burns, appropriate pain management will help in optimising pain control both in the early stages where skin grafting and debridement are being carried out and later when the patient requires assistance to undergo physiotherapy. In the patient with spinal cord injury, the initial phase following the injury is often complicated by acute neuropathic pain where early intervention is critical, while in the oncology patient, acute pain can complicate therapy, as in the patient who develops mucositis as a complication of treatment.

Providing Comprehensive Acute Pain Management

Acute and post-operative pain is best managed by an acute pain team and there are a number of structural models of how these are best set up and operated (Rawal and Allvin 1998). While many are headed by consultant anaesthetists, this is not always the case and often the day to day running of the team is managed by a specialist pain nurse, with medical staff used only for back up when necessary. Acute pain teams need to have clearly defined guidelines and major goals, which will be dictated in part by their institution and circumstances (see Clinical practice guidelines for Acute Pain teams, Cousins and Power 1999). Irrespective of how the team is organised there must be an efficient method of referral of patients either from the operating theatre or from the various surgical teams.

Clinical Practice Guidelines for Acute Pain Teams (Cousins and Power 1999)

Guidelines

  • A collaborative, interdisciplinary approach to pain control, including all members of the healthcare team and input from the patient and the patient’s family, when appropriate. An individualised proactive pain control plan developed preoperatively by patients and practitioners (since pain is easier to prevent than to treat)

  • Assessment and frequent reassessment of the patients pain

  • Use of both drug and non-drug therapies to control and / or prevent pain

  • A formal, institutional approach, with clear lines of responsibility

Major Goals

  • Reduce the incidence and severity of patients’ postoperative or post-traumatic pain

  • Educate patients about the need to communicate regarding unrelieved pain, so they can receive prompt evaluation and effective treatment

  • Enhance patient comfort and satisfaction

  • Contribute to fewer postoperative complications and, in some cases, shorter stays after surgical procedures

Where possible, the pain team should also be involved in pre-operative education of the elective surgical patient. At such a meeting, the patients’ fears and anxieties about pain should be addressed, as there is considerable evidence to suggest that patients who have the opportunity to speak about their concerns about post-operative pain prior to surgery do better and use less medication that control groups. A number of studies have consistently pointed out that pain is usually the major fear of patients undergoing surgery. During pre-operative assessment, at least in the elective patient, it is important to obtain a full medication history especially in relation to use of analgesic agents and the duration of such therapy. Tolerance to opioids can develop quickly and identifying patients who attend for surgery with a history of oral opioid use is important, as they will most likely have different analgesic requirements when compared to the opioid naïve individual.

The acute pain team also needs to be responsible for the overall post-operative management of the patient. This includes ensuring that regular monitoring and recording of physiological parameters occurs. Details such as oxygen saturation, respiratory rate and pain status need to be recorded regularly and reviewed. Pain scores can be recorded either numerically or by descriptors. It is important to record pain levels both at rest and on movement, since treatment strategies for these problems will differ. Movement pain in particular is better treated with adjuvant agents rather than opioids.

Accurate recording of physiological data in patients being treated for acute pain is mandatory. Sedation scores and respiratory rate are important in reducing the incidence of opioid induced toxicity. Pain management records or electronic data apparatus should also allow for the recording of any associated adverse events (such as nausea and vomiting) and record data in a form allowing regular or on-going audit. Such audits of acute pain patients should, where possible, allow not only for examination of the parameters already described but also for outcome measures. The acute pain team should supervise the transition from a parenteral to an oral analgesic regime. Likewise, members of the acute pain service must recognise when a patient might be suffering a Persistent Acute Pain state or undergoing transition from an acute to a chronic pain state and need referral to chronic pain specialists.

Post-operative care also involves being alert for warning signs, so called “red flags” that might indicate developing complications of the surgery or trauma. In patients previously well controlled using a particular analgesic regime, continuing episodes of unexpected pain requiring increasing doses of medication should alert the practitioner. Under these circumstances, an investigation should be made to elicit the cause of these events, which might be a result of complications of surgery or trauma. This should be diagnosed and treated directly, rather than merely increasing doses of analgesic drugs (Cousins and Phillips 1986).

Pre-emptive Analgesia

Much has been made of the usefulness of pre-emptive or preventive analgesia. The concept of providing analgesia prior to a surgical stimulus and thus reducing central sensitisation seems to be a logical and useful proposition and generated a great deal of initial enthusiasm (Dahl and Kehlet 1993; Woolf and Chong 1993). Unfortunately, subsequent controlled trials have failed to consistently demonstrate that any of the commonly used strategies are effective in reducing post-operative pain or analgesic use. These include the pre-operative administration of opioids, non-steroidal anti-inflammatory drugs and the provision of local analgesic neural blockade (Gill et al. 2001; Podder et al. 2000; Uzunkoy et al. 2001). Much research has been conducted in an effort to ascertain the reasons for this (Charlton 2002; Kehlet 1998; Kissin 1996). Some hypotheses that have been advanced include the suggestion that when local anaesthesia is employed in a pre-emptive setting, any failure to provide complete blockade will still allow sensitisation to occur (Lund et al. 1987). Another possibility is the timing between placement of the blockade and the commencement of surgery is critical, with a time interval of at least 30 min being required between drug administration and surgery (Senturk et al. 2002). One question that has not been fully answered is whether the use of pre-emptive analgesia might lead to a reduction in the number of patients progressing from acute to chronic pain states. Early studies such as that of Bach et al. (1988) suggested that this may well be the case and this has been supported by more recent reports (Obata et al. 1999).

Treatment Strategies-General

The principles of management of acute nociceptive pain are generally multi-modal. This implies using a number of agents, sometimes given by different routes, to maximise pain control. While pain control after some minor procedures can be controlled by non-opioids alone, opioids remain the main stay of moderate to severe pain management. The use of combinations of adjuvant analgesics also known as balanced analgesia, allows for a reduction in opioid dosage and thus side effects, which can be useful in managing some aspects of pain that can be less responsive to opioids alone.

With regard to the selection of a route of drug administration, whilst the use of the oral route might initially seem easiest, it is rarely used in the first instance. The variable bioavailability of oral products coupled with post-operative attenuation of gastrointestinal function and the possibly of superimposed vomiting, makes this route a poor choice initially. Parenteral administration is usually called for and the intravenous route is the preferred route of administration, often using patient controlled analgesia (PCA) devices.

Patient Controlled Analgesia

PCA, as a means of drug administration has to a degree revolutionised modern pain management. Although purchase of the devices represents a significant financial outlay, there are savings to be made in terms of medical and nursing staff time, as well as less tangible benefits, such as reducing the number of needle stick injuries for example. Importantly, patients generally feel positive about using PCAs (Chumbley et al. 1999), with most studies suggesting that the feeling of “being in control” was the most common reason for the high level of satisfaction (Albert and Talbott 1988). However, despite a number of inbuilt safety mechanisms, overdosage can still occur with these devices, and strict post-operative monitoring is imperative (Macintyre 2001). While the intramuscular route can be used for intermittent analgesia, the pharmacokinetics are often unattractive, requiring repeated injections. Furthermore, intramuscular analgesia is most often prescribed on a p.r.n. or “as required” basis, which perforce implies that the patient must be in a pain state before they request the medication – a situation that should be avoided. Finally, every intramuscular (or indeed subcutaneous) injection given presents a possibility for a needlestick injury to occur – another situation best avoided.

Epidural Analgesia

Much has been written about the risks and benefits associated with the use of epidural analgesia in the post-operative period and interpreting the results of these myriad studies conducted under varying circumstances is extremely difficult. There is no doubt that epidural analgesia provides a number of real advantages. It allows the use of drug combinations, which can be delivered close to appropriate receptor sites in the spinal cord (Schmid et al. 2000), it reduces the requirements of opioid analgesics (Niemi and Breivik 1998) and generally allows for a faster return of physiological function, especially gastrointestinal and respiratory status in the post-operative period. The degree to which this occurs appears to be dependent, at least in part, on the nature of surgery performed (Young Park et al. 2001).

However, more recently, despite the fact that there are considerable benefits associated with the use of epidural infusions, attention has focussed on the nature and incidence of complications associated with epidural infusions (Horlocker and Wedel 2000; Rigg et al. 2002; Wheatley et al. 2001). These complications can range from local or systemic infection through to haematoma formation and local or permanent neurological sequelae. The rates of the most serious complications of permanent nerve defects or paraplegia are quoted as between 0.005 and 0.03% (Aromaa et al. 1997; Dahlgren and Tornebrandt 1995). Again analysis of these data is difficult because of the number of variables involved. For example there is growing evidence that those people who develop epidural neurological complications frequently have significant pre-existing pathologies, which may predispose them to such complications. Lastly, there has been considerable debate about guidelines for epidural placement and removal in patients undergoing peri-operative anti-coagulation. This is especially so when fractionated or low molecular weight heparin products are employed, because of the possibility of increased risk of development of epidural haematoma under these circumstances. Again, the evidence is conflicting (Bergqvist et al. 1992; Horlocker and Wedel 1998). Patient controlled epidural analgesia is a means of pain management that combines the efficacy of epidurally administered drugs with the convenience of patient control.

Intrathecal Analgesia

The intrathecal route of drug administration can be useful both as a means of providing anaesthesia and for post-operative analgesia. Both opioids and local anaesthetic agents have been administered by this route. While the use of low doses of less lipophilic agents such as morphine is popular and gives prolonged post-operative care, the use of this route is not without risk, as there has been a rise in the number of cases of transient neurological symptoms following lignocaine use (Johnson 2000).

Pharmacotherapies

Opioids

With regard to the opioids, there has been an increase both in the range of drugs available and in their routes of administration. The traditional range of opioids such as morphine, pethidine and fentanyl has been augmented by drugs such as oxycodone and hydromorphone. None of these drugs are actually “new”, having been synthesised in some cases almost 100 years ago, but rather they have been re-discovered by a new generation of prescribers. Oxycodone in particular is available in a sustained release form that exhibits a useful biphasic pharmacokinetic profile. The role of pethidine (meperidine) in modern pain management continues to be problematic. While it still has a place under certain circumstances, it should be avoided as an agent for longer-term use, owing to its apparently increased abuse potential and the risk of accumulation of the excitatory metabolite norpethidine. The increased opioid armamentarium has also given scope for opioid rotation. Although this is a strategy primarily associated with chronic pain management, patients can develop a degree of tolerance to opioids even after a few days. Where continued opioid treatment is needed for whatever reason, switching opioids often results in enhanced pain control, often together with a reduction in dosage. Methadone is an interesting drug, which has generated some recent interest. Its unusual pharmacokinetic profile, with a long and unpredictable half-life of up to 72 h, makes it impracticable for use in the very early stages of acute pain. However it can be used in later stages where a long acting oral product is preferable. That the drug has activity at the NMDA receptor as well as the mu opioid receptor is well known. However it has always been difficult to assess to what, if any, extent this contributes to its analgesic effect and the fact that it has been shown to be of benefit in the treatment of other pain states such as phantom limb pain (Bergmans et al. 2002).

Non-Opioids

The non-opioids are a diverse group of drugs with differing modes of action and means of administration. Most show clear synergism with the opioids. Members of this group include tramadol, the non-steroidal anti-inflammatory drugs (NSAIDS), COX-2 inhibitors and ketamine.

Paracetamol

Paracetamol should be almost the universal basis of acute and post-operative pain control. A number of well controlled trials have clearly demonstrated that regular paracetamol, when given in a dose of 1 gm q.i.d. clearly reduces opioid requirements by up to 30%. Side effects are minimal and the drug is very well tolerated. In most countries it is available in both oral and rectal forms and in a small number a parenteral pro-drug propacetamol is also available.

The only real contraindication to the prescribing of paracetamol is impaired hepatic function, where the drug is probably best avoided. Much work has also been done on the efficacy of other drugs given in combination with paracetamol. In general, the analysis of trial data suggests that while the combination of codeine phosphate (60 mg) has benefits over paracetamol alone, the use of paracetamol with lower quantities seems to confer little benefit. Likewise, although the combination of paracetamol with dextropropoxyphene is widely used to treat more severe pain, many trials suggest that it too has little to offer above paracetamol alone.

Tramadol

Tramadol is unique amongst analgesic agents in having a dual action. Its main activity probably lies in enhancing the action of noradrenaline and 5-hydroxytryptamine at the spinal cord level, while it also has a very weak agonist activity at the mu receptor at supraspinal sites. Tramadol is a very useful drug for the management of mild to moderate pain and the fact that it can be given orally or by the intravenous or intramuscular routes further adds to its versatility. Its low addiction potential makes it a good choice for long-term use. Because of risk of precipitating serotonin syndrome, tramadol is probably best avoided in combination with many of the different anti-depressant medications, especially the SSRIs, although in clinical practice the real risk seems quite low. Recent studies have confirmed that it possesses significant synergy when combined with paracetamol and indeed a combination product is now available in some countries (Fricke et al. 2002). There are few studies available on the usefulness of combination of tramadol with opioids, although initial results appear encouraging (Webb et al. 2002).

Tramadol is also attractive because of its low abuse potential. Certainly in comparison to strong opioids, the incidence of abuse, dependence and withdrawal is considerably lower (Cicero et al. 1999). However a number of such cases have been reported, almost all of which were in patients with a pre-existing history of drug or substance abuse (Brinker et al. 2002; Lange-Asschenfeldt et al. 2002).

In the management of post-operative pain, all efforts should be made to reduce the incidence of post-operative nausea and vomiting, which is not only uncomfortable for the patient, but an can also lead to fluid imbalance, impaired respiratory function and electrolyte disturbances. In this regard the use of tramadol is somewhat problematic, as the incidence of nausea and vomiting is at least as high as with opioids (Silvasti et al. 2000; Stamer et al. 1997). However, some strategies have been suggested to attenuate this response including administration of an intra-operative loading dose (Pang et al. 2000) and slow IV administration (Petrone et al. 1999). Should management of tramadol induced nausea and vomiting require pharmacological intervention, recent studies suggest that members of the butyrophenone class such as droperidol might be a better choice than 5HT3 antagonists such as ondansetron, which might not only be less effective, but also antagonise tramadol’s analgesic effects.

Non-Steroidal Anti-Inflammatory Drugs

NSAIDs, Survey (NSAIDs) are widely used in acute pain management (Merry and Power 1995). While they may be used as the sole agent in mild pain, they are primarily employed as adjunctive medications in combination with opioids in moderate to severe pain states. Here their action both at central and peripheral sites complements opioid activity and they are especially useful in the management of pain associated with movement. There have always been concerns associated with the use of NSAIDs in the surgical patient because of the risk of the development of serious complications, especially renal impairment. However, careful patient selection and monitoring, the use of a product with a short half-life and restricting the duration of treatment to about 3 days greatly reduces the danger.

The discovery of the two isoforms of the cyclo-oxygenase (COX) enzyme has more recently led to the development of COX-2 specific inhibitors such as celecoxib and rofecoxib, with the aim of developing potent NSAIDs without significant associated gastrointestinal side effects. The majority of studies on these drugs have been conducted in outpatient populations and whether they offer any advantage over traditional NSAIDs in the management of post-operative pain is unclear. Even more recently, a parenteral COX-2 inhibitor (parecoxib) has been developed specifically for the management of post-operative pain and initial results of studies are encouraging.

Unfortunately, the cardiovascular safety of these products has recently come under scrutiny that has resulted in at least one (rofecoxib) being withdrawn from the market, owing to an increase in thrombo-embolic events associated with its use (Solomon et al. 2004). There is considerable discussion at present as to wheter this constitutes an individual drug effect or a class effect. These setback have not however prevented the development and release of other members of this group with improved safety profiles.

Ketamine

Ketamine is an important second line drug in the pain physician’s armamentarium. Well known as an anaesthetic agent, it has in the last decade or so found use as an analgesic product when used in sub-anaesthetic doses. The drug has some useful N-methyl-D-aspartate (NMDA) receptor antagonist activity and can also augment the action of opioids in the treatment of nociceptive pain. The usual psychomimetic effects of the drug are not usually a problem in the dosages employed, although the development and release of the S(+) might signal a resurgence in the interest of this drug.

Neuropathic Pain

Comprehensive acute pain management also entails the recognition and management of acute neuropathic pain. Neuropathic pain is most frequently seen as a sequela of long-term pathological states such as diabetes or herpes zoster infection (Bowsher 1991). However this is not always the case and acute neuropathic pain can be seen immediately following surgical procedures where peripheral nerves have been disrupted, such as in the post-thoracotomy syndrome, following specific events such as acute spinal cord injury or as evidenced by phantom limb pain following amputation. It is important to be alert for the signs or symptoms of neuropathic pain in the acute or post-operative phase (see Features suggestive of neuropathic pain after NHMRC 1999). Failure to diagnose such a condition will result not only in prolonged pain, but also most probably in the patient being given increasing doses of opioid medication in a futile effort to control the condition (Hayes and Molloy 1997).

Features Suggestive of Neuropathic Pain (After NH & MRC 1999)

  • Pain can be related to an event causing nerve damage

  • Pain unrelated to ongoing tissue damage

  • Sometimes a delay between event and pain onset

    • The pain is described as burning, stabbing, pulsing or electric-shock like

    • Hyperalgesia

    • Allodynia (indicative of central sensitisation)

    • Dysaesthesia

  • Poor response to opioids

  • The pain is usually paroxysmal and often worse at night

  • Pain persists in spite of the absence of ongoing tissue damage

Management of neuropathic pain can be complex and much has been written on the usefulness of various pain strategies. A wide range of drugs with differing pharmacological targets such as anti-convulsant medications, notably gabapentin and carbamazepine, anti-depressants and membrane stabilising agents such as Mexiletine/Mexitil have all been employed with varying success. Local anaesthetics such as lignocaine have all been found to be useful, especially in the acute case, where they can be administered as a subcutaneous infusion.

Specific Acute Pain States

There are some acute pain states that have been subject to more extensive research and whose symptomatology and pathogenesis follows recognised patterns. These include acute lower back pain, pain following chest trauma or thoracic surgery, compartment syndrome and the acute presentation of complex regional pain syndrome. There have also been significant advances in our understanding of acute pain mechanisms and the differentiation between visceral or somatic (deep or superficial) pain.

Summary

There have been a number of significant improvements in the management of acute and post-operative pain management during the past decade. To some degree this has been helped by the emergence of new drugs or, in some cases, whole new drug groups. However in the main, advances in acute and post-operative pain management have come about by recognising how to manage pain better with existing drugs, focussing on the use of drug combinations to maximise outcomes. There has also been a greater appreciation of the importance of diagnosing acute neuropathic pain, requiring a different approach. Those involved in pain management have embarked on a virtual crusade in an effort to convince health professionals that acute and post-operative pain can be and must be appropriately and successfully managed. Perhaps the most important lesson of all is an appreciation that all chronic pain must start as acute pain. Appropriate management of acute pain will therefore have the additional bonus of eventually reducing the worldwide burden of patients having to suffer debilitating chronic pain states.