Examples of non‐opioid drugs include paracetamol, aspirin and NSAIDs that are effective for mild‐to‐moderate pain. These drugs are especially effective for musculoskeletal and visceral pain (Twycross et al. [220]).

Examples of opioids for mild‐to‐moderate pain include codeine, dihydrocodeine, tramadol and low‐dose oxycodone (steps 2 and 3). These drugs are used when adequate pain management is not achieved with non‐opioids and are usually used in combination formulations. It is not recommended to administer another analgesic from the same group if the drug being used is not controlling the pain. Uncontrolled pain needs to be assessed and managed with the titration of an opioid by moving up the ladder. The exception to this would be if the patient was experiencing intolerable side‐effects on the weak opioid and an alternative drug might be beneficial.

Examples of opioids for moderate‐to‐severe pain include morphine, oxycodone, fentanyl, diamorphine, methadone, buprenorphine, hydromorphone and alfentanil.

The use of non‐opioid analgesics such as paracetamol or paracetamol combined with a weak opioid such as codeine is recommended for managing pain following minor surgical procedures or when the pain following major surgery begins to subside (McQuay et al. [144]). It is also used in cancer patients with pain related to the cancer itself, procedure or treatment‐related pain. Paracetamol can also be given rectally if the oral route is contraindicated. An intravenous preparation of paracetamol is now available and can provide effective analgesia after surgical procedures (Romsing et al. [192]). It is more effective and of faster onset than the same dose given enterally. The use of the intravenous form should be limited to patients in whom the enteral route cannot be used. With regard to dosing schedules for parenteral administration of paracetamol, the dose should be reduced for those who weigh 50 kg or under. For example, patients who weigh 33–50 kg should not exceed a maximum daily dose of 60 mg/kg, not exceeding 3 g. For patients over 50 kg with an additional risk factor for hepatotoxicity, the maximum daily dose should be 3 g in 24 hours, and for those patients over 50 kg with no risk factor then the maximum daily dose can be up to 4 g (Bristol‐Myers Squibb [23]).

Paracetamol taken in the correct dose of not more than 4 g per day is relatively free of side‐effects. When used in combination with codeine preparations, the most frequent side‐effect is constipation.

Non‐steroidal anti‐inflammatory drugs (NSAIDs) have been shown to provide better pain relief than paracetamol combinations for acute pain (McQuay et al. [144]). These drugs can be used alone or in combination with both opioid and non‐opioid analgesics. Two commonly used NSAIDs are diclofenac, which can be administered by the oral, parenteral, enteral or rectal route, and ibuprofen, which is available only as an oral or enteral preparation. The disadvantage of both of these is that often side‐effects such as coagulation problems, renal impairment and gastrointestinal disturbances limit their use. Newer COX‐2‐specific NSAIDs have the advantage that they have similar analgesic and anti‐inflammatory effects (Reicin et al. [184]) but have no effect on platelets or the gastric mucosa (Rowbotham [194]). As a result, coagulation problems and gastrointestinal irritation are likely to be significantly reduced. However, several of these drugs have been withdrawn from the market due to long‐term cardiovascular side‐effects and it will take time for newer products with an improved safety profile to re‐establish themselves in practice (Macintyre et al. [129]).

A meta‐analysis has suggested that there is little evidence to suggest that any of these drugs are safe in cardiovascular terms. Compared with placebo, rofecoxib was associated with the highest risk of myocardial infarction and ibuprofen with the highest risk of stroke followed by diclofenac. Diclofenac and lumiracoxib were associated with the highest risk of cardiovascular death. Naproxen is viewed as being least harmful for cardiovascular safety but this advantage should be weighed against gastrointestinal toxicity (Trelle et al. [216]). The decision to prescribe an NSAID should be based on an assessment of a person's individual risk factors, including any history of cardiovascular and gastrointestinal illness (NICE [154]). Naproxen (1000 mg a day or less) and low‐dose ibuprofen (1200 mg a day or less) are considered to have the most favourable thrombotic cardiovascular safety profiles of all NSAIDs. The lowest effective dose should be used for the shortest duration necessary to control symptoms. A person's need for symptomatic relief and response to treatment should be re‐evaluated periodically.

In studies, tramadol has been recognized as being efficacious in the management of chronic cancer pain of moderate severity (Davis et al. [47]).

It is uncertain whether tramadol is more effective than other opioids for mild‐to‐moderate neuropathic pain; one report suggests a reduction in allodynia (pain from stimuli which are not normally painful) (Sindrup and Jensen [206], Twycross and Wilcock [218]). It is uncertain whether tramadol is more effective in neuropathic pain than other opioids for mild to moderate pain (Dühmke et al. [58]). Tramadol has been associated with seizures, notably when the total daily dose exceeds 400 mg or when tramadol has been prescribed alongside other medications that may lower the seizure threshold, for example tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs) (Twycross et al. [220]). It is available in immediate‐ and modified‐release preparations. A warning about tramadol from the US Food and Drug Administration (FDA) suggested an increased risk of suicide in those patients who were emotionally unstable and in particular those already taking anti‐depressants and tranquillizers.

Codeine is metabolized by the hepatic cytochrome CYP2D6 to morphine. Approximately 7% of Caucasians and 1–3% of the Asian population are poor CYP2D6 metabolizers and therefore do not experience effective analgesia with codeine.

Codeine is available in tablet and syrup formulations. Doses of 30–60 mg po qds are generally prescribed to a maximum of 240 mg/24 h. It is also available in combination preparations with a non‐opioid. The combination preparations are available in varying strengths of codeine and paracetamol, including co‐codamol 8 mg/500 mg, 15 mg/500 mg and 30 mg/500 mg.

A large amount of information and research is available concerning morphine and therefore it tends to be the first‐line opioid (of choice). It is available in oral, rectal, parenteral and intraspinal preparations.

All strong opioids require careful titration from an expert practitioner. Where possible, modified‐release preparations should be used at regular intervals in the management of persistent pain (British Pain Society [BPS] [25]). For patients who are requiring in excess of 120–180 mg of morphine or equivalent, advice from a pain specialist should be sought. Patients should be informed of potential side‐effects such as constipation, nausea and increased sleepiness, in order to allay any fear. The patient should also be told that nausea and drowsiness are transitory and normally improve within 48 hours, but that constipation can be an ongoing problem and it is recommended that a laxative should be prescribed when the opioid is started.

Patients often have many concerns about commencing strong drugs such as morphine. Fears frequently centre around addiction and abuse (Cherny et al. [37]). Time should be taken to reassure patients and their families and verbal and written information provided (NICE [155]).

Although morphine is still considered to be the opioid drug of choice for moderate‐to‐severe pain (Hanks et al. [89]), alternative opioids allow the practitioner to carefully assess the patient on an individual basis and select the most appropriate one to use. From a palliative care perspective, guidance available from NICE supports safe prescribing of opioids (NICE [155]).

Fentanyl is a strong opioid, available in a patch, which is recommended in patients who have stable pain requirements. Transdermal patches are available in doses of 12, 25, 50, 75 or 100 μg per hour. It is reported to have an improved side‐effect profile in comparison to morphine in relation to constipation (Urban et al. [222]), although some patients experience nausea and mild drowsiness. Use of the patch has increased because it frees the patient from taking tablets.

Changing of the patch is recommended every 3 days but in some circumstances patients may require a dosing interval of 2 days (Urban et al. [222]). The patch should be applied to skin that is free from excess hair and any form of irritation and should not be applied to irradiated areas. It is advisable to change the location on the body to avoid an adverse skin reaction. Occasionally difficulties arise relating to the titration of the patch as each patch is equivalent to a range of morphine (Table 22.2).

Methadone is a synthetic opioid developed more than 40 years ago (Riley [187]). It is available in oral, rectal and parenteral preparations. There has been some reluctance amongst professionals to use methadone, which arose from the difficulties experienced in titrating the drug due to its long half‐life (15 hours) that caused accumulation to occur, especially in the elderly (Gannon [82]). There are different methods of achieving effective titration (Gannon [82]); for example, one regimen is to calculate one‐tenth of the total daily dose of morphine (maximum starting dose must not exceed 30 mg). Administer the methadone to the patient on an as‐required basis but not within 3 hours of the last fixed dose. The total dose required over a 24‐hour period is calculated after 5–6 days, divided and given as a two or three times daily regimen and this avoids the build‐up of methadone within the body (Morley and Makin [148]). Titration is recommended in a hospital setting to ensure accurate administration. This can be difficult for patients because they have to experience pain before they are administered a dose of methadone in the titration period.

Methadone can be a cheap, effective alternative to morphine if titration is supervised by the specialist pain or palliative care team (Gardner‐Nix [83]).

It is particularly useful in patients with renal failure. Morphine is excreted via the kidneys and, if renal failure occurs, this may lead to the patient experiencing severe drowsiness as a result of accumulation of morphine metabolites (Gannon [82]). Methadone is lipid soluble and is metabolized mainly in the liver. About half of the drug and its metabolites are excreted by the intestines and half by the kidneys. Methadone should be used with the advice of a pain/palliative care specialist.

Oxycodone is available as an immediate‐ or modified‐release preparation and titration should occur in the same way as morphine. Oxycodone is a useful alternative to morphine (Riley [187]). It has similar properties and can be administered orally, rectally and parenterally. Oxycodone has similar side‐effects and is usually given 4–6 hourly. It has an analgesic potency 1.5–2.0 times higher than morphine. It has similar side‐effects to morphine, although oxycodone has been found to cause less nausea (Heiskanen and Kalso [95]) and significantly less itchiness (Mucci‐LoRusso et al. [149]).

A study by Riley ([188]) identified that on a population level there is no difference between morphine and oxycodone in terms of analgesia efficacy and tolerability.

This drug is a combination of modified‐release oxycodone and naloxone. The aim of this combination is to prevent the potential negative effects of opioids on bowel function. It is suggested that approximately 97% of the naloxone is eliminated by first‐pass metabolism (the drug is absorbed into the gastrointestinal tract through the portal vein into the liver which means only a proportion of the drug reaches the circulation) in the healthy liver, preventing it from significantly affecting analgesic effects (Vondrackova et al. [227]).

Tapentadol is a centrally acting opioid analgesic supported by evidence for the management of acute and severe chronic pain (Schwartz et al. [203], Wild et al. [234]). It is available in oral preparations in immediate‐ and modified‐release forms. The conversion factor for tapentadol from oral morphine is 2.5:1. Therefore 10 mg oral morphine is equivalent to 25 mg of tapentadol. Side‐effects associated with tapentadol are similar to other opioids, including dizziness, headaches, somnolence, nausea and constipation.

Diamorphine is used parenterally in a syringe pump for the control of moderate‐to‐severe pain when patients are unable to take the oral form of morphine. It is calculated by dividing the total daily dose of oral morphine by three. Breakthrough doses are calculated by dividing the 24‐hour dose of diamorphine by six and administering on an as‐required basis (Fallon et al. [67]).

Buprenorphine is an alternative strong opioid available in patch form. The patch has similar advantages to fentanyl but does not contain a reservoir of the drug. Instead, it is contained in a matrix form with effective levels of the drug being reached within 24 hours. Titration is recommended with an alternative opioid initially and then transfer to the patch when stable requirements have been reached. A lower dose patch (Butrans) is available in strengths of 5, 10 and 20 μg/h that should be worn continuously by the patient for 7 days. The higher dose patch (Transtec) of 35, 52.5 and 70 μg/h is licensed to be used up to 96 hours or twice weekly for patient convenience. Conversion is based on the chart supplied by the pharmaceutical company which demonstrates equivalent doses. Buprenorphine is also available as a sublingual tablet, which is titrated from 200 to 800 μg 6 hourly. Conversion is based on multiplying the total daily dose of buprenorphine by 100 to give the total daily dose of morphine (i.e. 200 μg buprenorphine/8‐hourly = 600 μg buprenorphine/24 hours = 60 mg morphine/24 hours) (Budd [29]).

Transmucosal opioids such as fentanyl citrate (Actiq), Abstral, Effentora and intranasal preparations such as PecFent are licensed to be used for the treatment of cancer breakthrough pain. There are some circumstances when these agents are used off licence but they should always be used under the guidance of a specialist.

Licensed for the management of breakthrough pain in patients who are already on an established maintenance dose of opioid for cancer pain, oral transmucosal fentanyl citrate (OTFC) is a lozenge which is rubbed against the oral mucosa on the side of the cheek, leading to the lozenge being dissolved by the saliva. The advantage of OTFC is its fast onset via the buccal mucosa (5–15 minutes) and its short duration (up to 2 hours). It is available in a range of doses (200–1600 μg) but there is no direct relation between the baseline analgesia and the breakthrough dose. Titration can be difficult and lengthy as the recommended starting dose is 200 μg with titration upwards (Portenoy et al. [175]). It is recommended that the lozenge be removed from the mouth if the pain subsides before it has completely dissolved. The lozenge should not be reused but should be dissolved under running hot water.

Fentanyl buccal tablets are licensed medications for breakthrough pain in adults with cancer who are already receiving a maintenance opioid for chronic cancer. The brand names for these medications are Effentora and Abstral. Patients receiving maintenance opioid therapy are those who are taking at least 60 mg of oral morphine daily, at least 25 μg of transdermal fentanyl per hour, at least 30 mg of oxycodone daily, at least 8 mg of oral hydromorphone daily or an equi‐analgesic dose of another opioid for a week or longer.

Effentora buccal tablet is available in 100, 200, 400, 600 and 800 μg. It is placed on the oral mucosa above the third upper molar which leads to the tablet being dissolved by the saliva. It usually takes 15–25 minutes for the tablet to dissolve. It is recommended that if the tablet has not completely dissolved within 30 minutes then the remainder of the tablet should be swallowed with water as it is thought that the tablet will then only be likely to consist of inactive substances rather than active fentanyl (Darwish et al. [45]).

Abstral is an oral transmucosal delivery formulation of fentanyl citrate, indicated for the management of breakthrough pain in patients using opioid therapy for chronic cancer pain (Rauch et al. [182]). The tablet is administered sublingually and it rapidly disintegrates, ensuring the fentanyl dissolves quickly. Abstral is available in six dosing strengths: 100, 200, 300, 400, 600 and 800 μg fentanyl citrate.

Studies are currently examining the potential benefits of using cannabis for the management of chronic conditions, for example multiple sclerosis and cancer. There is some evidence for relief of spasticity and neuropathic pain and for improvement in sleep (Lynch and Campbell [127]). For those patients who may present wishing to use medications such as cannabis oil, local policies should be consulted.

By creating trusting relationships with patients, nurses are instrumental in reducing anxiety and helping patients to cope with pain. Nurses may underestimate the benefits and comfort they bring by staying with a patient who is experiencing pain (Mann and Carr [135]). Nurses can help to create a trusting relationship by:

Patient information/education can make all the difference between effective and ineffective pain relief. Information/education helps to reduce anxiety (Chapman [35]) and enables patients to make informed decisions about their care. Patients should be given specific information about why pain control is important, what to expect in terms of pain relief, how they can participate in their management and what to do if pain is not controlled. Some caution is required, however, because not all patients respond positively to the same level of information. Patients with high levels of anxiety may find that detailed information can increase their anxiety and influence their pain control. NICE guidance on the safe prescribing of opioids suggests that all patients who start on opioids should be offered written information to support them (NICE [155]).

This can be used to help patients manage pain and anxiety. It helps by engaging the patient in a more pleasant activity and provides distraction from the pain or may change the perception of a painful experience such as venepuncture/cannulation (Chapman [35]). Relaxation techniques are further discussed in the section on ‘Cancer‐related fatigue (CRF) and sleep’ in Chapter c27.

The use of music in the healthcare setting can also provide relaxation and distraction from pain (Heiser et al. [94]). Setting up a library of music (e.g. easy listening, classical) and having personal listening devices available for patient use is a simple way to provide patients with relaxing music. Vaajoki et al. ([224]) reported significantly lower pain intensity and pain distress in bedrest on the second post‐operative day in a music group compared with a control group after elective abdominal surgery.

A literature review highlighted that art therapy could be used to alleviate physical symptoms in some patients. Therapeutic art‐making was shown to be beneficial in improving the quality of life for patients. Art therapy allows patients emotional safety and assists them to resolve the personal struggles that contribute to their pain (Angheluta and Lee [3]).

Simple comfort measures such as positioning pillows and bedlinen (e.g. to support a painful limb) (Mann and Carr [135]) can help the patient feel more relaxed and improve patient comfort and pain control. Other comfort measures include ensuring that interruptions and noise are minimized to promote rest and ensuring the ambient temperature is comfortable.

Physiotherapy and occupational therapy can help to reduce pain and to improve function and quality of life for patients (BPS [25]). A variety of measures can be used for this including therapeutic exercise, pacing of daily activity and lifestyle adjustment (BPS [25]).

Transcutaneous electrical nerve stimulation (TENS) (Figure 22.4) is thought to work by sending a weak electrical current through the skin to stimulate the sensory nerve endings. Depending on the stimulation parameters used, TENS is thought to modulate pain impulses by closing the gate to pain transmission within the spinal cord by stimulating the release of natural pain‐relieving chemicals in the brain and spinal cord (King [115]).

Evidence for the use of TENS is variable. Johnson and Martinson ([113]) reported significant decreases in pain at rest and on movement in a meta‐analysis of 38 studies on TENS and peripheral nerve stimulation for chronic musculoskeletal pain. The evidence for TENS for post‐operative pain is often negative, but this may be due to how the studies are conducted.

For decades, superficial heat therapy has been used to relieve a variety of muscular and joint pains, including arthritis, back pain and period pain. There is much anecdotal and some scientific evidence to support the usefulness of heat as an adjunct to other pain treatments (French et al. [79]).

Heat works by:

In the home environment, people use a variety of different methods for applying heat therapies, such as warm baths, hot water bottles, wheat‐based heat packs and electrical heating pads. In the hospital setting, caution is required with this equipment as it does not reach health and safety standards (no even and regular temperature distribution) and there have been incidences of serious burns (Barillo et al. [8]). Carr and Mann ([32]) note that heat therapy should not be used immediately following tissue damage as it will increase swelling. The Medicines and Healthcare products Regulatory Agency (MHRA [145]) has documented evidence of burns caused by using heat patches or packs and therefore urges caution in their use and also recommends regular checking of skin throughout therapy.

Cold therapies can also be used to stimulate nerves and modulate pain (Carr and Mann [32]). Cold may be particularly valuable following an acute bruising injury where it can help to reduce inflammation and limit further damage. Cold can be applied in the form of crushed ice or gel‐filled cold packs which should be wrapped in a towel to protect the skin from an ice burn.