Pain 

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Pain is an essential sensation which has protected human beings an other living creatures for many centuries. People who have a reduced ability to feel pain are susceptible to damage to their bodies (e.g. diabetics). Despite pain being useful, it is of course extremely unpleasant. These pages explain some of the common causes of pain, what makes it worse and what makes it better. They explain the different types of pain killers and why they are given in different situations, which pain killers can be taken together and which combinations have to be avoided. The side effects of painkillers are explained together with advice on how to alleviate them.

Patients and carers with a better understanding of their pain killers are more likely to take them properly, have most benefit and have less side effects.

Types of cancer related pain

Tumour are generally not painful on their own. They cause pain by pressing on or damaging adjacent organs so the types of pain depends mainly on which organ or structure is being damaged. The description of pain one individuals description of pain in terms of character and severity varies enormously:-

Bone pain - A background constant pain (like tooth ache) made worse by moving or putting weight on the effected bone. In the legs, spine or hips this would be standing or walking for ribs this may be sneezing, coughing, taking a deep breath or lying on one side. Disease in the bone can increase the risk of fraction - the pain here would be more severe and often combined with swelling, bruising and disability.

Liver pain - In the right upper side of the tummy (abdomen) can extend under the ribs and across the front of the stomach area (upper central part of the abdomen). Can be associated with a pain in the right shoulder (this is called referred pain and does usually mean there's anything wrong with the shoulder). There is generally a dull ache associated with mild nausea but usually made worse in different positions or taking deep breaths, coughing or sneezing. It may be associate dwith signs of liver disease (see jaundice).

The lining of the lung - This is called the pleura and hence it is also called pleuritic pain. In the same way as rib pain this is made worse by walking for ribs this may be breathing, sneezing, coughing, taking a deep breath.

Nerve pain (neuropathic pain, neuralgia). Caused by pressure on or damage to nerves. Often associated with altered sensation or weakness. At first there may be increased sensation in the area of skin the nerve supplies. This is called hyperaesthesia and patient describe it as a burning sensation. As the nerve damage becomes more severe numbness develops. The pain is sharp and often "shooting down the affected limb". Sciatica for example is caused by pressure on the nerve roots which come from the lower pain. Many of us have experience this from time to time, the pain tends to shoot down the back of the legs.

Headaches 
There are several causes of headaches:-

• At the front of the head & face with a feeling of pressure - usually pressure in the sinuses.
• At the back of the head associated with pain in the neck - often caused by problems with the vertebrae in the
• Pain which comes in episodes associated with nausea, zig, zag or flashing lights. This sounds like migraine and patients may have a long history of similar episodes.
• A pain throughout the whole head or even just one side, sometimes "behind the eye" usually comes on as the day progresses - not relieved by simple medications.
• A mild headache, usually relieved by simple medications such as paracetomal & aspirin. Made worse by lying flat and often relieved by standing up. This type of headache may be associated with nausea and is caused by increased pressure within the fluid surrounding the brain - patients should present to their doctor immediately.
• Any headaches associated with loss or interference with vision, sensation, muscle power, seizures or altered co-ordination should be reported to your doctor.

Indigestion is the feeling of discomfort or pain within the lower chest of abdomen (Tummy) caused by an abnormality or disjunction of the gut or bowel.  There are several other causes of pain within the abdomen from other organs such as the pancreas, lymph nodes, liver, kidney, spleen or aorta but this page only deals with those caused by the gut itself.

The following list summarises some of the causes and advice on some other medications used to alleviate the symptoms. The types of indigestion can be split into four main categories depending on which part of the gut  is affected:-

• Gullet (oesophagus)

Food getting stuck (dysphagia) - Initially this is mainly meat or dry bread but if severe can be softer foods or even liquid. Food getting stuck is often accompanied by pain. If these symptoms develop although there are many causes, it is important to present to your doctor as one of them is cancer.

Heart burn - A burning feeling in the center of the chest, sometimes combined with an acid taste in the back of the mouth. Usually may worse by eating a large meal, straining or leaning forward. This is a long standing problem in many people caused by acid from the stomach refluxing back into the gullet. The steroids which are given with chemotherapy often make this symptom worse or even bring it on in patients who have not previously experienced it. Often medication is prescribed to prevent this symptom - click on the headings in the adjacent column. There are also several practical manoeuvres which can be performed. These include; Eating small meals often - see diet & indigestion.  Putting two bricks under the head of the bed. Avoiding   tight clothing around the abdomen.

• Stomach

Classic indigestion comes on shortly after food and is a described burning discomfort in the top of the abdomen which tends to come and go. Often helped by antacid medication (white medicine). This is caused by irritation of the stomach wall (gastritis) again which can be aggravated by steroids given with the chemotherapy -  see diet & indigestion. Often medication is prescribed to prevent this symptom - click on the headings in the adjacent column.

If there is vomiting several hours after food and the food is clearly not digested this may be due to an obstruction of the stomach - gastric outlet obstruction. You doctor should be aware of this.

• Duodenum

• Small bowel

• Large bowel

• Lower rectum

A feeling of fullness in the back passage. May be associated with a blood on the stool or a mucous discharge form the back passage. Often caused by radiotherapy to the lower pelvis can be help with suppositories  such as xyloproct or scheriproct - ask your doctor.

 Analgesia for chronic pain

Analgesics for chronic pain should always be prescribed regularly, not just when required. It is important to take the correct painkillers for your specific type and level of pain.  The World Health Organisation issued guidelines describing 3 steps in analgesic prescribing, the "analgesic ladder":-

*A co-analgesic is a drug (or device) which may or may not have intrinsic analgesic activity, but which when used with conventional analgesics may contribute significantly to pain relief. If pain is difficult to control always review the addition of co-analgesics

Patients should start on step 1,2, or 3  depending on the severity of their pain

Where pain is persisting or increasing, despite the use of co-analgesics, a patient's analgesics should be changed to those on a higher step on the ladder: where pain is improving analgesics should be reduced and/or changed to those on a lower step on the ladder.

A) Step 1a - non prescription (over the counter pain killers)

Despite the wide range of over the counter products available the active painkiller ingredients are one of the 4 following drugs used alone, in combination with each other or with other drugs:-

• Paracetamol
• Aspirin
• Codeine
• Ibuprofen

    Step 1b - Non morphine drugs +/- co-analgesia*

Paracetamol 1g qds, Aspirin 600 - 900 mg qds

Volterol 50 mg qds (or another suitable non-steroidal analgesic - see NSAI section)

 B) Step 2 - weak morphine-like drugs

• Dihydrocodeine
• Codeine
• Dextropropoxyphene

These may used in combination formulations with non-opioids for patient convenience eg:-

Coproxamol (paracetamol 325 mg + dextropropoxyphene 32.5 mg) - 2 tablets qds

Tylex / Solpadol (paracetamol 500 mg + codeine 30 mg) - 2 tablets qds

Alternatively prescribe two drugs separately

Dihydrocdeine 30 - 60 mg qds + Paracetamol 1g qds

The use of the following drugs is to be discouraged as they contain sub-therapeutic doses of weak opioids:

C) Step 3 -  Analgesics for severe pain: morphine preparations and dose titration (STRONG OPIOIDS)

Before prescribing strong opioid analgesics, always ascertain whether the patient would achieve adequate symptom control on a weak opioid +1- a coanalgesic

• morphine
• phenazocine
• diamorphine
• methadone

Oral morphine is the drug of choice in the majority of patients with severe pain. Oral morphine preparations

a) Immediate release (Prescribe regularly 4 hourly)

• morphine elixir Oromorph / morphine elixir
• morphine tablets Sevredol (10 & 20 mg only)
• morphine suppositories

b) Controlled release

• Morphine sulphate MST continuous A 12 hourly slow release drug better for long term administration because gives a sustained release over the day.
• Morphine sulphate MXL 24hour slow release table
• TTS fentanyl patch (Durogesic) - a patch which sticks to the skin releasing the opioid painkiller over 72 hours.

 Tips to start morphine and convert and titrate immediate release to controlled release morphine:-

1. For patients with uncontrolled pain, always start with 4 hourly immediate release morphine to enable rapid titration. This is true both for patients who have previously been on MST and for those starting morphine for the first time.
2. The prescription of a double dose (or 11/2 x dose in the elderly) at night stops the patient being woken in the middle of the night and is usually effective.
3. Prescribe breakthrough (PRN) immediate release morphine at the same dose as the 4 hourly dose.
4. There is no limit to the number of doses required.
5. For inpatients, prescribe a range for immediate release morphine so that the nurses can titrate the dose as required

Converting to MST from oral morphine or its equivalents.

Oral morphine - To convert  to MST, once the pain is adequately controlled on 4 hourly immediate release preparations. Add up the total morphine requirement in the previous 24 hours and divide by 2 to get the morning and evening MST doses ie. exactly 12 hours apart. For breakthrough pain, always prescribe immediate release morphine at the equivalent 4 hourly dose. For intravenous morphine divide by 4 to to get the morning and evening MST doses.

a) Important side effects

• Constipation Always prescribe aperients. All patients will need a combination of a softener and a stimulant, eg :-

Codanthramer capsules* 1-4 bd

Codanthramer suspension* 10-40 mls bd

Codanthramer strong capsules* 1-4 bd

Docusate 100 - 200 mg tds

Bisacodyl 5 - 10 mg bd

Milpar 10 - 20 mls bd

Senna 2 - 4 tabs bd

* Avoid danthron, containing aperients (codanthramer) in patients who are incontinent or who have an indwelling catheter, because of the risk of danthron burns

Titrate the laxative dose as required for the individual patient.

• Nausea and vomiting - Usually wears off after 24 - 48 hours

Prescribe prophylactic antiemetic e.g. Haloperidol 1.5 mg nocte

Domperidone 10 - 20 mg tds

Metochlopramide 10 - 20 mg qds

• Drowsiness and confusion - Usually wears off after 24 -48 hours

Warn patient and reassure

5. Opiold prescribing in renal impairment

Morphine is metabolised to morphine-3-glucurnnide (M-3-G) and morphine-6-glucuronide (M-6-G). While M-6-G has traditionally been regarded as the active metabolite of morphine, current research has shown that M-3-G may also have some activity. Both metabolites are renally excreted, and accumulate in renal impairment, causing toxicity

Suggested management strategies are:

a) Prescribe smaller doses of opioid analgesic. N.B. the dose reduction required will depend on the degree of renal impairment

b) If there are still problems with toxicity, administer small doses of opioid less frequently, i.e. 6-8 hourly.

c) Convert to phenazocine which is metabolised to inactive products in the liver

6. Alternatives to oral morphine for severe pain

Very few patients are truly morphine intolerant

There is no place in the routine management of chronic cancer pain for short acting opiold analgesics such as pethidine and dextromoramide

If the pain is not responding to morphine always consider the aetiology of the pain and review the use of coanalgesics

a) Phenazocine - For patients who have unacceptable drowsiness/nausea on oral morphine preparations, a trial of phenazocine may be indicated.

• Conversion :- Oral morphine (20-25 mg): Phenazocine (5mg)

The starting dose of phenazocine is usually 2.5 mg 6-8 hourly

Breakthrough phenazocine should be prescribed and should be equivalent to the 6-8 hourly regular dose

The dose of phenazocine should be titrated by 2.5 mg increments as guided by the number of breakthrough doses required/day

• Prophylactic aperients and antiemetics should be prescribed in the usual way.

b) Transdermal Fentanyl - TTS Fentanyl is a new synthetic opioid preparation and may be considered in the following patient groups:

Stable opioid requirements but unacceptable constipation. Mood disturbance nausea & vomiting number of tablets. Unable to swallow. Fentanyl is unsuitable in patients with:

• rapidly changing opioid requirements e.g. dose titration
• renal or hepatic impairment
• chronic skin disorders
• patients with limited dexterit

When converting to patches from oral morphine, patients will usually require three 4 hourly doses until the subcutaneous depot has built up. Proximate conversions from oral morphine to transdermal fentanyl are as follows:-

Converting to fentanyl patches from slow release morphine.

e.g. MST 60 mg bd = TTS fentanyl patch 25 mcg/hr the 'breakthrough' dose of sevredol = 20 mg as required

IMPORTANT - A subcutaneous depot of fentanyl persists for up to 24 hours after patch removal. Patients converting from TTS fentanyl back to mophine should not restart regular oral morphine for at least 12 hours after the patch has been removed, but may have it when required - pm.

The first fentanyl patch needs to be applied at the same time as the last dose of MST. Breakthrough Sevredol / Oramorph should be prescribed with TTS fentanyl, at the breakthrough dose that would be needed it the patient was taking the equivalent dose of MST.

7. The use of syringe drivers for subcutaneous infusions

Many drugs are well absorbed subcutaneously, and this route removes the need for intravenous cannulation in terminally ill patients and is particularly useful in those with dysphagia, persistent vomiting, bowel obstruction patients too weak to take oral medication

Diamorphine More soluble in solution, so better absorbed than morphine subcutaneously

• Conversion:

Oral morphine (3): Subcutaneous diamorphine (1)

• Diamorphine can be mixed with:-

a) Antiemetics;

haloperidol

cyclizine*

metoclopramide

methotrimeprazine*

b) Sedatives

midazolam

c) Antimuscarinics

hyoscine

atropine

glycopyrronium hydrobromide

d) other;

octreotide

dexamethasone*

* These drugs must only be mixed with a total volume of at least 48 mls using a 10 or 20 ml syringe. The same principle should apply to the other listed drugs to avoid precipitation. NOTE:-

· Dexamethasone and cyclizine cannot be mixed with octreotide

· Cyclizine can precipitate, especially in maximum dose (150 mg/day), and the syringe driver must be checked regularly.

• The needle insertion site should be viewed each time the pump is changed, and the site rotated every 48 hours, or sooner if required.
• There are various pump durations, but If a patient is discharged home on a syringe driver then this will almost certainly need to be converted to a 24 hour pump.

8. Coanalgesics: Bone pain

Radiotherapy is the treatment of choice for painful bone metastases and should be considered in conjunction with coanalgesics. Further treatment options for bone pain are as follows:

Local anti-inflammatory action (inhibitors of prostaglandin synthesis)

If previous peptic irritation prescribe prophylactic H2 blocker or misoprostol (NB. PR/topical routes do not protect from systemic toxicity)

Diclofenac and Naproxen are the NSAIDs of choice as both have a good toxicity profile, and in particular less GI toxicity than most other NSAIDs

Ketorolac is a potent anti-inflammatory which can be administered subcutanously, and may be beneficial even when other NSAIDs have been ineffective: Always give test dose of 25 mg sc. prior to infusion maximum 24 hour dose = 90 mg by continuous sc. infusion.

Anti inflammatory +/- anti-tumour action

Start with high dose  but try to reduce to lowest effective dose to avoid toxicity

Always prescribe a H2 blocker or misoproslol if used in conjunction with NSAID.

Potent inhibitors of osteoclast-mediated bone resorption. The most commonly used bisphosphonates are pamidronate and clodronate - click here for details on bone hardening drugs. Assess response after 2-3 doses, and continue in responding patients until no further benefit.

9. Coanalgesics: Neupathic pain

Pain associated with dysaesthesia (numbness): start antidepressant

Shooting pains: start anticonvulsant

2nd line: add in anti-arrythmic

a) Antidepressant:

Central and peripheral action on serotonin and noradrenalin mediated neurotransmission

Give at night and build up dose gradually to avoid excess sedation. Start with low dose and increase every 3 - 5 days

e.g. Amitriptyline 25 - 150 mg nocte

Dothiepin 25 - 150 mg nocte

b) Anticonvulsants (best prescribed under the supervision of a pain specialist)

Membrane-stabilising action

Start at low dose and gradually increase to avoid sedation and central toxicity

e.g. Carbamezepine 100 - 400 mg bd/tds

Sodium Valproate 200 - 600 mg bd/tds

c) Anti-arrythmics (best prescribed under the supervision of a pain specialist)

Membrane-stabilising action

Avoid flecainide if there is a history of ischaemic heart disease ECG should be performed prior to starting treatment

e.g. Flecainide 100-200 mg bd

Mexilitine 200 mg tds

d) Ketamine d) Ketamine (best prescribed under the supervision of a pain specialist)

Further general information Your doctors and specialist nurses are in an ideal position to give you relevant information on your disease and treatment as they know your individual circumstances. Cancerbackup has a help line (0808 800 1234) and a prize winning video available in English, Italian, Urdu, Bengali, Gujarati & Hindi explaining Radiotherapy & Chemotherapy. Cancernet.co.uk has over 500 pages describing cancer, its management, practical tips and tool which patients, their carers and their doctors have found helpful during the cancer journey.