• Relieve acute, severe pain promptly before fuller assessment and management.
• Diagnose the cause and type of pain as accurately as possible. This is required to plan the most effective treatment.
• Always consider treating the underlying cause of pain. This may involve a greater burden for the person but has a greater potential benefit. Drugs or treatments that are not directly analgesic may be used (such as radiotherapy for bone pain) and can help to reduce the amount of standard analgesics needed.
• Treat pain symptomatically. A stepwise approach using the World Health Organization's analgesic ladder can be used as a framework. Pain should always be relieved promptly and effectively with standard analgesic drugs, even when other treatments are given for pain.
• Some types of pain require a specific symptomatic approach (for example, neuropathic pain, bone pain, myofascial pain).
• Seek specialist help promptly if pain proves difficult to manage.

• Immediately relieve pain, using a subcutaneous or slow intravenous dose of a strong opioid.
• The dose depends on the person's comorbidities and their existing analgesia:
• If the person is opioid naive, consider a subcutaneous or slow intravenous dose of 2 mg of diamorphine (1–2 mg if the person is elderly or frail).
• If the person is already taking a regular opioid, calculate the 4-hourly dose by taking the total dose given over the previous 24 hours (including doses required for breakthrough pain but excluding those for incident pain) and dividing it by six, and then give the equivalent subcutaneous dose of diamorphine or morphine:
• The subcutaneous dose of diamorphine is one third of the 4-hourly oral morphine dose.
• The subcutaneous dose of morphine is approximately half of the 4-hourly oral morphine dose.
• For more detailed information on changing the dose of oral morphine to a subcutaneous dose, see the conversion table in Switching from morphine to another strong opioid.
• Following this, seek immediate specialist palliative care advice regarding further management and try to determine the cause of the pain.
• Always take into account the person's circumstances and wishes:
• If the person wishes to stay at home and is near the end of life, then control of symptoms should be attempted in this setting; if this is not possible, transfer to a hospice or hospital may be needed.

• There is no expert consensus on how to manage a person with acute, severe pain. Opinion varies widely with respect to the preferred drug, route of administration, and doses used.
• CKS has offered a simple pragmatic approach for immediate management based on opinion from expert reviewers.

• Discuss pain with the person directly if possible. The person, if competent and able to communicate, is the most reliable source of information on their pain. If it is not possible to ask them (because of cognitive impairment or communication deficits, for example), the family or healthcare professionals may be able to help with the assessment, bearing in mind that family members may overestimate, and healthcare professionals may underestimate, the person's pain.
• Assess each pain a person has, bearing in mind that there may be more than one. Seek specialist advice if assessment is difficult because of complex or multiple pains.
• Assess pain regularly, particularly if it is not adequately controlled.
• Review the medical history and medical records to determine the known site and extent of the cancer. Pain occurring distant from the previously known sites of cancer may indicate either a non-malignant cause or secondary spread of the cancer.
• Assess the influence of psychological, social, and spiritual factors on the person's experience of pain.

• This recommendation is based on expert opinion [Regnard and Hockley, 2004b; SIGN, 2008].

• Use a validated structured pain assessment tool, for example:
• Numerical rating scale — mark on a scale of 0 (no pain) to 10 (worst possible pain) how strong the pain is.
• Visual analogue scale — mark on a 10-cm line (with 'no pain' at one end and 'worst possible pain' at the other end) how strong the pain is.
• The score can be correlated to the severity of the pain:
• Mild pain: less than 3 out of 10 on a visual analogue scale or numerical rating scale.
• Mild to moderate pain: 3–6 out of 10 on a visual analogue scale or numerical rating scale.
• Severe pain: more than 6 out of 10 on a visual analogue scale or numerical rating scale.
• Differentiate between the person's usual level of pain, breakthrough pain, incident pain, and 'end of dose' failure of regular around-the-clock analgesia. End of dose failure usually occurs at the same time each day, usually just before the next dose is due.

• These recommendations are based on expert opinion.
• To assess the response to treatment, it is useful to have some measure of the severity of pain before and after an intervention [Abu-Saad and Courtens, 2001]. Pain rating scales may be useful to assess the course of a person's pain, assess the effects of treatment, and reassure the person that their pain is being thoroughly addressed [IAHPC, 2004]:
• A guideline on the control of pain in adults with cancer from the Scottish Intercollegiate Guidelines Network (SIGN) recommends that people with cancer pain should have treatment outcomes monitored regularly using visual analogue scales, numerical rating scales, or verbal rating scales [SIGN, 2008]. This recommendation was based on expert opinion and non-analytic studies.
• There is no universally accepted tool for the assessment of cancer pain. Standardized pain assessment tools that have been recommended by the European Association of Palliative Care for use in research and clinical practice include visual analogue scales, numerical rating scales, and verbal rating scales [Caraceni et al, 2002]. These are also valid tools for measuring pain in very elderly or cognitively impaired people, and those who are dying [SIGN, 2008].
• CKS has adopted the classifications of severity of pain given (on the basis of expert opinion) in the SIGN guideline [SIGN, 2008]. However, it is acknowledged that these definitions are subjective, and clinical judgement is therefore needed.

• Enquire about:
• Site and number of pains.
• Radiation.
• Quality.
• Timing (onset, duration, breakthrough or incident pain).
• Exacerbating and relieving factors.
• Associated symptoms and signs.
• The person's thoughts about the likely cause.
• Pain that presents insidiously and progressively worsens suggests a malignant cause for the pain.
• Acute onset of pain may be of a non-cancer related cause (for example, pulmonary embolism, myocardial infarction, perforation of a viscus). Cancer-related causes include pathological fracture, bleeding into hepatic metastases, or spinal cord compression.
• The quality of the pain and exacerbating features can also suggest a cause.

• CKS found no trial evidence but have based this recommendation on expert opinion in a palliative care guideline [NHS Fife, 2006a] and a guide to symptom management in palliative care [Regnard and Hockley, 2004a].

• Assess the effect of the pain on activities of daily living, mood, and sleep.
• Identify factors contributing to the person's distress (for example, anxiety, depression, other physical symptoms, family or carer distress).

• This recommendation is based on expert opinion in reviews [Spiegel et al, 1994; Abu-Saad and Courtens, 2001; Qaseem et al, 2008].

• Enquire about:
• Response to previous analgesia (including allergies or sensitivities).
• Use of over-the-counter or complementary therapies and other prescribed medication.
• The person's treatment preferences (for example, preferred route of administration, a wish not to experience sedative effects from medication so that they can remain mobile).
• Concerns of the person and their family (for example, regarding opioid use).

• CKS found no trial evidence to support this recommendation but have offered this advice as a pragmatic approach because all these factors will affect the person's management.

• Examine the person, if appropriate. A full examination is rarely appropriate in people who are very unwell and in the last stages of life.
• Look particularly for specific points of tenderness (which may indicate the site of origin of the pain) and signs of neurological deficit which may suggest spinal cord compression.

• This recommendation is based on expert opinion in guidelines [Ellershaw, 2006; NHS Fife, 2006a] and the Oxford textbook of palliative care [Foley, 2004].

• Consider investigations that are appropriate to the person's condition.
• Limit investigations to those likely to significantly affect treatment decisions.
• If the person is near the end of life, investigations are rarely indicated. They may be performed if a reversible condition may be the cause of their deterioration, or if the person has acute (potentially reversible) deterioration.
• If investigations are appropriate, ensure that the person's pain is adequately treated before they undergo diagnostic procedures. For more information on how to prescribe for incident pain (such as pain on movement), see Management of breakthrough pain.

• This recommendation is based on expert opinion in guidelines [IAHPC, 2004; Cancer Care Alliance, 2006b; Ellershaw, 2006] and the Oxford textbook of palliative care [Foley, 2004].

• Prescribe analgesia for continuous pain on a regular basis, in addition to as-required analgesia.
• Consider a stepwise approach, using the World Health Organization (WHO) analgesic ladder. Start at the appropriate point of the analgesic ladder, moving up the ladder when the maximum dose at each step is reached until the person is comfortable. The steps are:
• Non-opioid analgesic: paracetamol and/or nonsteroidal anti-inflammatory drug (mild pain).
• Weak opioid, with or without a non-opioid analgesic (mild-to-moderate pain).
• Strong opioid, with or without a non-opioid analgesic (severe pain).
• At any stage, consider the addition of a non-opioid adjuvant drug (any drug that has a primary indication other than for pain management but is analgesic in some painful conditions: for example, a tricyclic antidepressant for neuropathic pain).
• Review regularly (consider a telephone call if appropriate), step treatment up or down as necessary, and stop unnecessary medication that has not worked.

• The recommendation to use analgesia at regular intervals for continuous pain is based on the British National Formulary and Palliative Care Formulary [Twycross and Wilcock, 2007; BNF 56, 2008].
• This stepwise approach is based on the principles of the WHO analgesic ladder (based on the consensus of international expert opinion and clinical practice) that aims to match treatment to the intensity of the pain [WHO, 1996; WHO, 2003]. When the WHO ladder is used appropriately, at least 70% of people achieve benefit [Quigley, 2005].
• The correlation of mild, moderate, and severe pain to the steps of the WHO ladder is used in a guideline from the Scottish Intercollegiate Guidelines Network [SIGN, 2008]:
• Non-opioid analgesic drugs: trial data of non-opioid (paracetamol and nonsteroidal anti-inflammatory drugs [NSAIDs]) analgesia in people with cancer-related pain are limited, but evidence supports the general analgesic effect of these drugs [MeReC, 2000; Bandolier, 2007; McNicol et al, 2007], and guidelines and experts recommend their use. Non-opioid analgesic drugs may have synergistic effects when used with opioids, allowing better pain relief to be achieved at lower doses of opioid and therefore reducing opioid adverse effects [SIGN, 2008].
• Weak opioid drugs: there is debate about the use of weak opioids at step 2 of the WHO analgesic ladder because there is little evidence that they are more effective than the drugs (paracetamol and/or an NSAID) used at step 1 [MeReC, 2000]. However, weak evidence suggests that using an opioid in combination with paracetamol, with or without an NSAID, may reduce the dose of opioid required and therefore reduce adverse effects [SIGN, 2008]. An alternative strategy is to prescribe a low dose of a strong opioid. This approach may be more effective in relieving pain, but there is more potential for adverse effects.
• Strong opioid drugs: the success of the WHO approach to pain management has been attributed to using strong oral opioids for severe pain [Hanks et al, 2001].

• Paracetamol and/or a nonsteroidal anti-inflammatory drug (NSAID) are recommended first line.
• If an NSAID is appropriate and not contraindicated:
• Ibuprofen, diclofenac, and naproxen are the NSAIDs of choice.
• The oral route is preferred, but if this is not possible, consider alternative routes (such as rectal).
• Consider prescribing a proton pump inhibitor with an NSAID. For more information on minimizing the risks associated with NSAID treatment, see the CKS topic on NSAIDs - prescribing issues.
• Non-opioid adjuvant drugs may also be useful for some people with specific pain types; see Management of specific types of pain.

• CKS found no good-quality evidence that NSAIDs have a better benefit/harm ratio than paracetamol in cancer-related pain. Few comparative studies have examined their relative efficacy and adverse effects with long-term use, and most published data are from single-dose studies [McQuay and Moore, 1997].
• Paracetamol: a Cochrane review examined the use of paracetamol in cancer-related pain and found insufficient trial data to make firm conclusions [McNicol et al, 2007].
• NSAIDs: a Cochrane review assessed the effect of NSAIDs in the treatment of cancer-related pain and found that NSAIDs are effective for short-term treatment of cancer-related pain [McNicol et al, 2007]. Insufficient studies were found to make conclusions about their long-term use.
• Diclofenac, naproxen, and ibuprofen are recommended. They are widely considered to have acceptable adverse effect profiles [CSM, 2002]. Standard NSAIDs other than ibuprofen, diclofenac, or naproxen are associated with a higher risk of gastrointestinal adverse events [Henry et al, 1996; Hernández-Diaz and Rodriguez, 2000; CSM, 2003]. Modified-release products are relatively more expensive.
• CKS has not recommended cyclo-oxygenase 2–selective NSAIDs because there is no evidence that they offer any advantage in terms of pain control compared with standard NSAIDs [Davis et al, 2005]. If gastrointestinal safety is a concern and an NSAID is thought to be necessary, CKS recommends a standard NSAID plus a proton pump inhibitor. For more information, see the CKS topic on NSAIDs - prescribing issues.

• Codeine or dihydrocodeine is recommended:
• If flexibility of dosing and titration of analgesic effect are required, prescribe the weak opioid separately to paracetamol.
• If compliance is likely to be a problem and analgesic requirements are stable, consider prescribing a product combining 500 mg of paracetamol with 30 mg of codeine.
• To prevent constipation, prescribe a stimulant laxative (such as senna or bisacodyl) and a softening laxative (such as docusate).
• A laxative with both properties (for example, co-danthramer or co-danthrusate) is also an option.
• Avoid dantron-containing laxatives in people who are incontinent as these drugs can cause a chemical burn (reddening) of the perianal area.
• Dantron can also colour the urine red and alarm the person.

• CKS recommends codeine and dihydrocodeine because in clinical practice they are of equivalent potency and have approximately the same duration of action [Twycross and Wilcock, 2007; SIGN, 2008].
• The recommendation to use a laxative is based on expert opinion in the Palliative Care Formulary [Twycross and Wilcock, 2007] and reviewers.

• Use the oral route of administration where possible.
• Morphine is recommended.
• For advice on how to initiate morphine and titrate the dose, see Initiation of oral morphine and Titration of oral morphine.
• If the person's compliance with oral morphine is good, but pain is inadequately controlled:
• Review the cause of the pain.
• Consider using a non-opioid adjuvant drug to treat a specific type of pain. See Management of specific types of pain.
• If compliance with oral morphine is good, but the person cannot tolerate an adequate dose, consider using an alternative oral opioid — seek specialist advice.
• If the oral route is not appropriate (for example, the person has nausea and vomiting, or cannot swallow, or has poor compliance with oral analgesia), consider:
• Switching to a subcutaneous diamorphine or morphine infusion. For more information, see Switching from morphine to another strong opioid.
• Switching to transdermal fentanyl if the person has stable analgesic requirements and has previously tolerated opioids — seek specialist advice.
• When prescribing a strong opioid:
• Prescribe an anti-emetic (such as metoclopramide for gastric stasis, otherwise low-dose haloperidol):
• If the person has experienced nausea with a previous opioid, give regularly for the first week to prevent opioid-induced nausea and vomiting and then reassess, or
• If the person experiences nausea with morphine but has not experienced nausea with a previous opioid, prescribe for use on an as-required basis for 1 week.
• To prevent constipation, prescribe a stimulant (such as senna or bisacodyl) and a softening laxative (such as docusate).
• A laxative with both properties (for example, co-danthramer or co-danthrusate) is also an option.
• Avoid dantron-containing laxatives in people who are incontinent as these drugs can cause a chemical burn (reddening) of the perianal area.
• Dantron can also colour the urine red and alarm the person.
• Seek specialist palliative care advice if:
• There is doubt about how to manage a person's pain.
• Adverse effects limit treatment and cannot be adequately managed.
• An unfamiliar opioid or route of administration is being considered.
• The pain is still at 50% or more of its starting level after 2 weeks.

• The recommendations in this section are consistent with expert opinion in palliative care pain management guidelines [MeReC, 2003; NHS Quality Improvement Scotland, 2004; NHS Argyll & Clyde, 2005; Pan-Glasgow Palliative Care Algorithm Group, 2007a; Pan-Glasgow Palliative Care Algorithm Group, 2007b; SIGN, 2008] and a chapter from the ABC of palliative care [Colvin et al, 2006].

Route of administration

• Expert opinion suggests that for analgesic drugs, the oral route is the simplest and preferable [Quigley, 2005].
• If the person cannot take oral morphine, a subcutaneous infusion of opioid is an option because it is probably as effective as intravenous infusion (based on weak evidence) but is easier to administer [SIGN, 2008].
• Expert opinion in palliative care guidelines suggests that if pain is stable and the person cannot take oral medication, transdermal opioid administration can be considered [Hanks et al, 2001; SIGN, 2008].

Choice of drug

• Morphine is generally accepted by palliative care organizations and expert opinion to be the strong oral opioid of choice for managing moderate and severe cancer-related pain [Zech et al, 1995; Hanks et al, 2001; Davis et al, 2005; Quigley, 2005; Wiffen and McQuay, 2007]. It is usually well tolerated, has well-established efficacy and safety in clinical practice, and is familiar to most practitioners [SIGN, 2008]. Morphine is available as a wide variety of oral formulations, allowing flexibility in dosing regimens. It is also the most cost-effective strong opioid analgesic available. No other opioid has been shown to have greater analgesic effect, although use of opioids via the transdermal route have been found to result in less constipation [Tassinari et al, 2008].
• CKS has not recommended alternative oral strong opioid drugs to oral morphine because there is a lack of evidence from high-quality comparative trials to suggest greater benefit in terms of efficacy or adverse effects [SIGN, 2008].
• CKS recommends diamorphine as the opioid of choice for subcutaneous infusion, as it is much more soluble than morphine and therefore easier to administer in higher doses [Twycross and Wilcock, 2007; SIGN, 2008]. Subcutaneous morphine sulphate has been used as an alternative to diamorphine owing to unpredictable manufacturing problems:
• For people with stabilized severe pain who express a preference for a patch formulation or people who cannot take oral morphine, fentanyl patches may be appropriate if the pain is stable [SIGN, 2008]. The Medicines and Healthcare products Regulatory Agency has issued advice that fentanyl patches should be used only in people who have previously tolerated opioids because there is a risk of significant respiratory depression in people who are opioid naive [MHRA, 2008]. Because of these safety issues, CKS recommends seeking specialist advice before starting fentanyl patches.

Anti-emetics and laxatives

• This recommendation is based on expert opinion in the Palliative Care Formulary [Twycross and Wilcock, 2007] and reviewers.

• Give adequate instructions (written if possible) on how to control breakthrough pain. Inform other healthcare team members, including out-of-hours staff, as appropriate.
• The person should take breakthrough analgesia before the pain gets severe, as it may take 30–60 minutes for the analgesia to reach full effect.
• When deciding whether more than one breakthrough dose is needed, consider the time required for medication to take effect and its potential for adverse effects before administering another dose.
• In a person taking regular analgesia, breakthrough pain indicates a need for reassessment of the analgesic dosage and the underlying cause of pain. For more information on how to increase the dose of oral morphine, see Titration of oral morphine.
• If the person is taking regular paracetamol and/or a nonsteroidal anti-inflammatory drug (NSAID), consider:
• Treating with an additional dose of the regular analgesic as long as it does not exceed the maximum licensed dose, or
• Adding in a weak opioid on an as-required or regular basis.
• If the person is taking regular paracetamol and/or an NSAID plus a weak opioid, consider:
• Treating with an additional dose of the regular analgesic as long as it does not exceed the maximum licensed dose, or
• Switching to a strong opioid.
• For people taking oral morphine:
• If the person is using immediate-release or modified-release morphine regularly — treat with immediate-release oral morphine (tablets or liquid), at a dose of one tenth of the total daily oral morphine dose, to be taken when required and repeated no more than 2-hourly.
• The breakthrough dose may need to be individually titrated to between 5% and 20% of the regular daily dose.
• If the person is in severe pain and needs another dose sooner than 2 hourly, seek specialist advice.
• The onset of action of immediate release morphine is about 20–30 minutes; this may not be ideal for those patients with rapid onset severe episodes of breakthrough pain. An immediate-release fentanyl product may be useful in these circumstances. However, immediate-release fentanyl products should only be started by a specialist because:
• There are four immediate release fentanyl products available, all with different routes of absorption: transmucosal lozenges (Actiq^®), sublingual tablets (Abstral^®), buccal tablets (Effentora^®), and intranasal (Instanyl^®).
• These products are not bioequivalent and cannot be substituted for one another.
• The rescue dose needs to be individually titrated — there is no correlation between the regular dose of strong opioid and the effective rescue dose.
• Serious adverse effects and deaths can occur if the products are not used correctly, or if they are used in opioid naive individuals, or for transient pain (such as migraine).
• These products are markedly more expensive than immediate release morphine.
• If the person is receiving a subcutaneous infusion of diamorphine or morphine:
• Treat with a subcutaneous bolus dose at one tenth of the 24-hour infusion dose, when required, and repeated no more than 2-hourly. If the person is in severe pain and needs another dose sooner, seek specialist advice.
• Oramorph^® is an alternative for people who can manage liquids but are on an infusion because they cannot swallow tablets. It allows the person and their family greater control over managing episodes of breakthrough pain without having to wait for a healthcare professional to attend to give a breakthrough subcutaneous dose. Specialist advice should be sought in this situation to check the oral route is appropriate and to clarify the dose of Oramorph^® because the doses suggested by experts vary.
• If using other strong opioid analgesics, seek specialist advice.
• If the person's background pain is satisfactorily controlled but they experience incident pain (pain on movement or particular events, such as micturition, wound dressing, bed care, travel):
• Do not keep increasing the 24-hour dose of opioid.
• Give a breakthrough dose of an immediate-release opioid approximately 30 minutes before the precipitating factor occurs. In some situations, immediate release fentanyl can be useful for this purpose, but this should be used only on the advice of a specialist.
• Do not include the breakthrough doses administered for incident pain when reassessing maintenance opioid analgesia requirements.

• Different strategies are used to reduce the impact of breakthrough pain, and expert opinion varies. This recommendation is based on expert opinion in palliative care pain management guidelines [IAHPC, 2004; Lothian Palliative Care Guidelines Group, 2004; NHS Quality Improvement Scotland, 2004; NHS Argyll & Clyde, 2005; Cancer Care Alliance, 2006b; Cancer Care Alliance, 2006a; Pan-Glasgow Palliative Care Algorithm Group, 2007a; SIGN, 2008], the British National Formulary [BNF 56, 2008], the Palliative Care Formulary [Twycross and Wilcock, 2007], a textbook on symptom relief in palliative care [Regnard and Hockley, 2004a], and feedback from expert reviewers.
• CKS found no trial evidence or published expert opinion to guide management if the person is taking paracetamol, an NSAID, a weak opioid, or any combination of these. The advice offered is therefore a pragmatic approach.
• Traditionally (evidence based on expert opinion and case studies) a breakthrough dose of oral morphine of one sixth of the total 24-hour dose (equivalent to the 4-hourly dose) has been used [SIGN, 2008]. However, now that modified-release products are available, many centres have found that using a more measured approach of using 10% of the total daily regular dose as the as-required breakthrough dose provides a better balance of top-up analgesia with adverse effects. More recent editions of the Palliative Care Formulary [Twycross et al, 2009] and the British National Formulary [BNF 59, 2010] now advocate this approach.
• Feedback from expert reviewers is that immediate-release fentanyl products should only be started under the supervision of a specialist. Although they have a faster onset of action than immediate-release morphine [Zeppetella and Ribeiro, 2006; Davies et al, 2009], they are not bioequivalent, the dose must be individually titrated, and serious adverse effects and deaths have been reported when they are incorrectly used [Twycross et al, 2009].
• Expert opinion from a reviewer suggests that giving breakthrough analgesia for incident pain requires a lot of cooperation, coordination, and planning of movements and caregiving with the carers but can be very successful.

• Consider whether there is a treatable underlying cause (for example, nerve compression from bone metastases or soft-tissue disease) and seek specialist advice regarding further treatment of the cause (for example, surgical stabilization for bone metastases or radiotherapy for soft-tissue disease).
• If pain is purely neuropathic and reversible conditions (for example, vitamin B₁₂ deficiency) have been excluded:
• Consider offering amitriptyline (off-label use) or pregabalin (or gabapentin if there is a local decision to prefer gabapentin over pregabalin).
• Titrate the dosage according to response and tolerability.
• For further information, on contraindications, cautions, managing adverse effects, and second-line options if amitriptyline or pregabalin are not effective, see the CKS topic on Neuropathic pain - drug treatment.
• If pain is of mixed origin, use standard analgesics in addition to a tricyclic antidepressant or pregabalin (or gabapentin) if pain is not adequately controlled with standard analgesia alone. See Non-emergency management of persistent pain.
• Seek specialist advice or consider referral if pain persists.

Treating the underlying cause of neuropathic pain

• The recommendation to manage any treatable causes of neuropathic pain is based on a textbook on symptom relief in palliative care [Regnard and Hockley, 2004a], a chapter from the ABC of palliative care [Colvin et al, 2006], a textbook of symptom management in advanced cancer [Twycross and Wilcock, 2001], and the Palliative Care Formulary [Twycross and Wilcock, 2007].

Management of neuropathic pain

• If pain is purely neuropathic and reversible conditions (for example, vitamin B₁₂ deficiency) have been excluded, CKS recommends that neuropathic pain should be managed in accordance with guidance issued by National Institute for Health and Clinical Excellence (NICE) on drug treatment of neuropathic pain in adults in non-specialist settings [NICE, 2010]. For further information, see the CKS topic on Neuropathic pain - drug treatment.
• Having reviewed the evidence for a number of neuropathic conditions (including cancer pain and neuropathic cancer pain), the NICE guidance development group (GDG) treated the term 'neuropathic pain' as a blanket condition regardless of the underlying cause; the GDG considered this to be helpful and practical for non-specialist healthcare professionals and patients. However, condition-specific recommendations were made if robust evidence on clinical efficacy and cost-effectiveness existed (as in the case of painful diabetic neuropathy), or where the evidence was clearly uncertain and insufficient to alter current clinical practice (as in the case of trigeminal neuralgia). The GDG acknowledged that evidence for treating a particular neuropathic pain condition with a particular aetiology is often extrapolated to other neuropathic pain conditions with other aetiologies, although there is little evidence to support the validity of this [NICE, 2010].

Persistent neuropathic pain

• CKS recommends seeking specialist advice for people with persistent neuropathic pain because various additional treatments may be considered for use by specialists, including cognitive behaviour therapy, ketamine, methadone, nerve blocks, or spinal analgesia.

• Consider whether a treatable underlying cause is present.
• Discuss with an oncologist regarding the need for radiotherapy.
• Use standard analgesics in a stepwise approach. See Non-emergency management of persistent pain.
• Also consider a trial of dexamethasone at a dose of 8–16 mg daily (taken in the morning), titrated down to the lowest dose that controls symptoms:
• If the volume of tablets or injection is difficult to manage in a single dose, it is acceptable to split the dose, in which case it should be given at 8 a.m. and 12 p.m. (noon).
• Have a low threshold for considering gastroprotection with a proton pump inhibitor.
• Response to dexamethasone should be assessed after 5–7 days, but extensive cerebral oedema may take 2–3 weeks to resolve.
• If there has been no response, discontinue dexamethasone immediately.
• If there has been a benefit, review frequently and reduce to the lowest dose that controls symptoms (for example, reduce by 2 mg every fifth day).

• This recommendation is based on expert opinion in guidelines on palliative care pain management [Lothian Palliative Care Guidelines Group, 2004; NHS Quality Improvement Scotland, 2004; NHS Argyll & Clyde, 2005; NHS Fife, 2006b; Pan-Glasgow Palliative Care Algorithm Group, 2007a; Pan-Glasgow Palliative Care Algorithm Group, 2007b] and a chapter in the ABC of palliative care [Colvin et al, 2006].
• The recommendation to have a low threshold for giving a proton pump inhibitor is based on expert opinion from reviewers, who suggested that most people with increased intracranial pressure will have risk factors for gastrointestinal bleeding as well as corticosteroid treatment.

• Consider whether there is a treatable underlying cause:
• It may be possible to treat certain causes of colicky pain (for example, bowel colic due to constipation) in primary care — see the CKS topic on Palliative cancer care - constipation.
• However, some causes (for example, bowel obstruction) need specialist management and possibly surgical intervention, provided the person is fit enough for surgery and wants to be admitted.
• If symptomatic management is appropriate, consider hyoscine butylbromide (an antispasmodic).
• There is no agreement among experts in terms of dose or route of administration. Suggested doses are:
• 10–20 mg as a subcutaneous dose as required, repeated 2-hourly, or
• 40–300 mg as a subcutaneous infusion over 24 hours via a syringe driver.
• If the oral route is preferred, consider mebeverine 135 mg three times a day.

• This recommendation is based on expert opinion in palliative care pain management guidelines [NHS Argyll & Clyde, 2005; Pan-Glasgow Palliative Care Algorithm Group, 2007a], a textbook on symptom relief in palliative care [Regnard and Hockley, 2004a], the British National Formulary [BNF 56, 2008], and feedback from expert reviewers.
• Experts do not advise the use of oral hyoscine butylbromide for this purpose because it has very poor oral bioavailability. Mebeverine has been offered as an option for the oral route on the basis of expert opinion.

• Consider whether there is a treatable underlying cause and discuss with an oncologist if this is suspected (for example, regarding radiotherapy for bone metastases).
• Seek urgent advice from an orthopaedic surgeon if there is evidence or suspicion of an actual or imminent fracture.
• For symptomatic relief:
• Apply hot or cold packs.
• Use standard analgesia in a stepwise approach (see Non-emergency management of persistent pain).
• If incident pain occurs on movement, encourage the person to take a dose of their breakthrough analgesia 20–30 minutes before anticipated movement. See Management of breakthrough pain.
• If pain is difficult to manage, seek advice from a specialist (such as a palliative care specialist or an anaesthetist with an interest in chronic pain).

• This recommendation is based on palliative care pain management guidelines [Cancer Care Alliance, 2006b; NHS Quality Improvement Scotland, 2004; NHS Argyll & Clyde, 2005; NHS Fife, 2006b; Pan-Glasgow Palliative Care Algorithm Group, 2007a], a chapter from the ABC of palliative care [Colvin et al, 2006], and a textbook on symptom management in advanced cancer [Twycross and Wilcock, 2001].
• CKS recommends seeking specialist advice if pain is difficult to manage because various additional treatments are available in secondary care, including radiotherapy, a bisphosphonate, or nerve block.

• Consider whether there is a treatable underlying cause.
• Try simple measures (such as heat pad, massage, relaxation).
• Consider transcutaneous electric nerve stimulation over a trigger point if the pain is myofascial.
• If trigger points are multiple or the muscle spasm is widespread, consider a muscle relaxant — diazepam or (less preferred) baclofen:
• Several different doses of diazepam have been suggested by experts. These range from 2–10 mg at night to 2–5 mg three times a day; the higher doses may be helpful if there is co-existing anxiety. The dose may need to be reduced depending on clinical response.
• The suggested dose of baclofen to treat muscle spasm is 5–10 mg three times a day. However, baclofen should be titrated slowly, which may limit its usefulness in people requiring palliative care.
• Choice of drug will also depend on any other actions (for example, diazepam may be more appropriate for people with co-existing anxiety) and potential for adverse effects. For more detail, see the prescribing information sections on Baclofen and Diazepam.
• If these measures are not effective, or there are only a few trigger points, consider referral. Other drugs or injection of trigger points with local anaesthetic may be considered in secondary care.

• There is no clear evidence that any muscle relaxant drug is superior to any other [Twycross and Wilcock, 2007].
• The recommended drugs and doses are based on expert opinion in guidelines [NHS Quality Improvement Scotland, 2004; NHS Argyll & Clyde, 2005; Cancer Care Alliance, 2006b; Pan-Glasgow Palliative Care Algorithm Group, 2007a], a textbook on symptom management in advanced cancer [Twycross and Wilcock, 2001], the British National Formulary [BNF 56, 2008], and expert opinion from reviewers.

• Suspected spinal cord compression is a medical emergency. In order to preserve physical function, it must be diagnosed and treated before there is significant neurological compromise.
• Suspect spinal metastases if any of the following features are present:
• Pain in the middle (thoracic) or upper (cervical) spine.
• Progressive lower (lumbar) spinal pain.
• Severe unremitting lower spinal pain.
• Spinal pain aggravated by straining (for example, when passing stool or when coughing or sneezing).
• Localized spinal tenderness.
• Nocturnal spinal pain preventing sleep.
• Suspect spinal cord compression if any of the following features are present:
• Neurological symptoms (including radicular pain, any limb weakness, difficulty in walking, sensory loss, or bladder or bowel dysfunction).
• Neurological signs of spinal cord or cauda equina compression.

• This recommendation is based on the National Institute for Health and Clinical Excellence guideline Metastatic spinal cord compression [NICE, 2008].

• If spinal metastases are thought to be the cause of the pain, seek urgent (within 24 hours) specialist advice from a metastatic spinal cord compression coordinator if available, or alternatively the person's palliative care consultant or oncologist.
• If there are associated neurological features suggestive of spinal cord compression, seek immediate specialist advice.
• Unless contraindicated (including a significant suspicion of lymphoma), offer all people with metastatic spinal cord compression a loading dose of 16 mg of dexamethasone as soon as possible after assessment.

• This recommendation is based on the National Institute for Health and Clinical Excellence guideline Metastatic spinal cord compression [NICE, 2008].