Cancer pain and opioid treatment

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Cancer pain is a clinical syndrome, not a dose problem. Ask the patient to identify each pain separately and describe what provokes it, what it prevents and whether it is continuous or incident. Palpate bone and soft tissue, map sensory change and weakness and examine the abdomen and spine. A new pattern may reveal fracture, cord compression, obstruction, infection or treatment toxicity; escalating an existing prescription before examining the change can delay reversible treatment.

Mechanism directs therapy. Somatic bone or tissue pain is localised and often worsens with movement. Visceral pain is deep, diffuse or colicky and may be referred. Neuropathic pain burns, shocks or produces allodynia and sensory deficit. Most advanced cancer pain is mixed. Treat the tumour when possible through radiotherapy, surgery, systemic therapy, bisphosphonate, drainage or stabilisation while using analgesia to restore sleep and function during the delay to response.

NICE recommends oral morphine as first-line strong opioid for many adults with advanced progressive disease. Agree goals, explain regular and breakthrough components and prescribe constipation prevention from the first dose. Titrate using pain, function, rescue use and toxicity rather than pain intensity alone. Renal failure, frailty, delirium, swallowing difficulty, previous opioid exposure and interacting benzodiazepine, gabapentinoid or alcohol use alter the initial choice and require specialist pharmacy or palliative input.

Opioid rotation is a safety-critical calculation. Total every opioid used in 24 hours, convert through a current local table, account for route and reduce for incomplete cross-tolerance before dividing the new schedule. Methadone has non-linear conversion and QT and interaction risk and belongs with specialists. A fentanyl patch changes slowly after application and remains active after removal. Every switch needs written rescue, monitoring and escalation instructions.

Key points

Assess pain by site, onset, quality, radiation, severity at rest and movement, breakthrough pattern, sleep and function; examination and investigation must explain a new pattern.
First exclude emergencies: cord compression, fracture, intracranial pressure, obstruction, infection, thrombosis and serious treatment toxicity need anatomical or cause-specific rescue.
Classify somatic, visceral, neuropathic and incident pain because opioids, anti-inflammatory treatment, adjuvants, radiotherapy, surgery and procedures address different mechanisms.
For moderate-to-severe pain from advanced progressive disease, oral morphine is the NICE first-line strong opioid when oral treatment and renal function permit.
In an opioid-naive adult, a typical starting total oral morphine dose is 20 to 30 mg per day with 5 mg immediate-release rescue; start lower in frailty and seek specialist advice in renal impairment.
Prescribe immediate-release rescue alongside regular opioid and review total use; repeated rescue need usually prompts reassessment and proportionate regular-dose adjustment, not an unlimited repeat supply.
Start a regular laxative when a strong opioid starts, and offer an antiemetic if nausea occurs; tolerance develops to some nausea and sedation but not reliably to constipation.
Use modified-release oral morphine for stable background pain or regular immediate-release during titration according to patient preference and service capability; both require breakthrough access.
Transdermal fentanyl is useful for stable opioid-responsive pain when swallowing or adherence makes oral medicine unsuitable, but it is not a rapid-titration patch for an opioid-naive crisis.
Neuropathic pain may need duloxetine, amitriptyline, gabapentin or pregabalin selected by comorbidity and interaction; specialist radiotherapy, nerve block or neuraxial treatment can reduce opioid burden.
Before an opioid switch, calculate the current 24-hour oral-morphine equivalent, check renal and liver function and reduce the calculated equianalgesic dose for incomplete cross-tolerance with specialist verification.
Pain on movement from unstable bone will not be made safe by sedation; protect loading and obtain surgical or radiotherapy review.
New difficult rousing or slow breathing requires withheld opioid, airway and ventilation support and titrated naloxone, followed by observation longer than the antagonist effect.
Review benefit against alertness, bowel function, falls, driving, adherence and patient goals; taper a regular opioid gradually when pain resolves or harm exceeds benefit.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Direct tumour injury

Bone, nerve, viscera, skin and soft-tissue invasion causes nociceptive, neuropathic or mixed pain through pressure, inflammation, ischaemia, fracture and tissue destruction.

Cancer-treatment injury

Surgery, radiotherapy, chemotherapy, endocrine, immune and targeted treatments can produce acute mucositis, neuropathy, myalgia, fibrosis, lymphoedema, insufficiency fracture and chronic post-procedural pain.

Concurrent non-cancer disease

Osteoarthritis, migraine, diabetic neuropathy, constipation, infection and vascular disease remain common and may need different treatment despite occurring during active cancer.

Total-pain amplification

Fear, depression, insomnia, isolation, financial strain and loss of role alter attention and coping, intensifying suffering without implying that physical pain is imagined.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Somatic nociception
Inflammatory mediators activate peripheral nociceptors in bone, skin and muscle, producing localised aching or movement-related pain that is often tender and mechanically informative.
2
Visceral nociception
Distension, capsule stretch, obstruction and ischaemia activate poorly localised autonomic afferents, causing deep pressure, colic, nausea, sweating and referred pain.
3
Neuropathic signalling
Tumour or treatment damages nerve, root, plexus or cord, generating burning, electric shocks, allodynia and sensory change that responds incompletely to opioid alone.
4
Sensitisation and opioid adaptation
Persistent input increases spinal and central excitability, while tolerance and rarely opioid-induced hyperalgesia can reduce benefit and increase diffuse pain during repeated dose escalation.
5
Opioids modulate pain networks
Mu-receptor activation reduces transmitter release and pain perception but also suppresses brainstem respiration and gut motility, linking analgesia to sedation, constipation and overdose risk.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Somatic bone or soft-tissue pain

Localised aching, tenderness and movement-related exacerbation indicate tissue nociception; severe functional pain in a long bone also warns of instability.

Visceral pain

Deep, poorly localised pressure, cramping, referred discomfort and autonomic nausea or sweating suggests capsule stretch, obstruction, ischaemia or organ infiltration.

Neuropathic pain

Burning, electric shocks, pins and needles, allodynia and sensory or motor change along a nerve, root or plexus indicate neural injury.

Breakthrough or incident pain

A transient flare despite controlled background pain may be spontaneous or triggered by movement, coughing, dressing or another predictable activity.

Opioid toxicityRed flag

Increasing drowsiness, respiratory slowing, hallucination, delirium, myoclonus or pinpoint pupils after dose, organ or interaction change requires urgent medicine review.

Total pain

Severe suffering with fear, insomnia, isolation or financial and family strain requires psychological, social and spiritual care alongside physical treatment.

Red flags requiring action

Back pain with weakness, gait change, sensory loss or bladder or bowel dysfunction requires immediate metastatic-spinal-cord-compression assessment and whole-spine MRI.
Sudden movement-related long-bone pain, inability to weight bear or deformity indicates impending or completed pathological fracture and needs urgent orthopaedic stabilisation review.
Severe new headache, vomiting, focal deficit, seizure or falling consciousness can reflect intracranial pressure, haemorrhage or infection and requires emergency imaging.
Rapidly increasing abdominal pain with guarding, vomiting, obstipation, fever or hypotension suggests obstruction, perforation, ischaemia or sepsis rather than uncomplicated cancer pain.
Respiratory rate below 8 per minute, difficult rousing, cyanosis or pinpoint pupils after opioid exposure requires immediate ventilation support and proportionate naloxone.
New pain during immunotherapy, bisphosphonate, anticoagulant or steroid treatment may signal immune toxicity, jaw osteonecrosis, bleeding, infection or fracture and should not be masked by extra opioid.
Escalating dose without analgesia, prominent allodynia or pain spreading beyond the original site raises tolerance, opioid-induced hyperalgesia, progression or a misclassified mechanism.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
First-line multidimensional pain assessmentFirst stepFirst line
Why
Define each pain’s mechanism, severity, breakthrough pattern, functional effect, current exposure, understanding and psychosocial context.
Interpretation and limitations
Record pain at rest and movement, rescue response and a functional goal; a numerical score without mechanism or examination cannot guide safe escalation.
02
Focused neurological and skeletal examination
Why
Identify weakness, sensory level, radicular deficit, focal tenderness, load pain and instability requiring emergency imaging or stabilisation.
Interpretation and limitations
Any neurological progression activates the MSCC or intracranial pathway; inability to load a long bone warrants protection and urgent radiography or CT.
03
Cause-directed imaging
Why
Use MRI, CT, radiography or ultrasound to answer a specific concern such as compression, fracture, obstruction, collection or progression.
Interpretation and limitations
Choose urgency from physiology and red flags; routine restaging is not a substitute for emergency whole-spine MRI or site-specific structural imaging.
04
Renal, liver, calcium and inflammatory assessment
Why
Find opioid accumulation risk and metabolic, infectious or skeletal contributors when pain or cognition changes.
Interpretation and limitations
Declining eGFR can accumulate morphine metabolites; hypercalcaemia, sepsis, dehydration and hepatic failure may cause both pain and toxicity and require parallel correction.
05
Formal opioid reconciliation
Why
Calculate every regular, rescue, patch, injection and over-the-counter sedative exposure before titration or rotation.
Interpretation and limitations
Convert the total previous 24 hours using a current local table and obtain independent specialist verification for high doses, methadone, renal failure or unusual routes.
06
Specialist procedural assessment
Why
Determine whether radiotherapy, stabilisation, nerve block, epidural, intrathecal, neurolytic or ablative treatment can target the generator.
Interpretation and limitations
Refer early when incident pain or toxicity prevents systemic titration; procedure selection depends on anatomy, coagulation, infection, prognosis and patient preference.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Oncological emergency

Cord compression, pathological fracture, raised intracranial pressure, bowel obstruction, infection, thrombosis and treatment toxicity present with pain and require cause-specific urgent treatment.

Non-malignant musculoskeletal pain

Degenerative joint, tendon, muscular and spinal disorders may fit examination and imaging better than progression and should receive proportionate rehabilitation and local care.

Neurological or vascular pain

Post-herpetic neuralgia, diabetic neuropathy, radiculopathy, ischaemia and venous thrombosis can coexist with cancer and need targeted investigation rather than automatic opioid escalation.

Opioid toxicity or withdrawal

Sedation, hallucination, myoclonus and hyperalgesia suggest accumulation, while sweating, diarrhoea, anxiety and diffuse ache after interruption can represent withdrawal.

Psychological and existential distress

Panic, depression, trauma and fear of dying intensify suffering and deserve direct treatment alongside, not instead of, physical analgesia and disease assessment.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01New or changed painDiagnose the generator before escalatingFirst stepEscalationPain appears, changes character or becomes difficult to control.

1Assess each site, mechanism, rest and movement severity, function, neurological and skeletal signs, bowel pattern, current medicines and psychosocial distress.
2Activate emergency imaging and specialist pathways for cord, brain, fracture, obstruction, infection or treatment toxicity and protect unsafe movement while anatomy is clarified.
3Treat the cause through cancer therapy, surgery, radiation, drainage or antimicrobial treatment while starting mechanism-appropriate analgesia and a documented review time.

02Starting a strong opioidPair analgesia with rescue and preventionModerate-to-severe cancer pain persists despite appropriate non-opioid and cause-directed measures.

1First lineAgree a functional goal, check previous opioid, renal and liver function, frailty, breathing, sedatives and ability to swallow and select oral morphine first line when suitable.
2Start a low regular schedule with immediate-release rescue, prescribe a regular laxative and explain nausea, sedation, driving, storage, dependence and overdose warning signs.
3EscalationReview within days using total rescue, pain at rest and movement, alertness, respiration and bowel function, then titrate, rotate or add local and neuropathic treatment rather than escalating blindly.

03Opioid rotationConvert total exposure with a safety reductionPain remains uncontrolled, toxicity emerges or renal, route or swallowing circumstances require a different opioid.

1Add all opioid delivered during the previous 24 hours and reassess whether progression, impaction, hyperalgesia, delirium or an untreated generator explains apparent failure.
2Use the current service conversion table, reduce the calculated equianalgesic dose for incomplete cross-tolerance and obtain specialist verification for high dose, methadone, organ failure or patch conversion.
3Provide a compatible rescue dose, stop overlapping formulations at the correct time and review early for withdrawal, sedation, respiration, analgesia and accumulation.

04Suspected opioid toxicitySupport ventilation and reverse proportionatelyA patient is difficult to rouse, breathes slowly or develops marked neurotoxicity after opioid exposure.

1Stop further opioid, call for emergency help, use airway and ventilation support, check glucose and identify renal decline, sepsis, dehydration, patch, pump or sedative co-exposure.
2Give titrated naloxone when respiratory depression is clinically important, aiming to restore ventilation rather than abruptly abolish all analgesia and precipitate severe withdrawal.
3Observe beyond naloxone duration, repeat dosing or infusion when required and rebuild a lower safer analgesic plan with treatment of the precipitant.

Key medicines and prescribing safety3 treatments · regimens, roles and cautions

NICE first-line strong opioid for many adults with moderate-to-severe pain from advanced progressive disease who can take oral treatment.

Oral morphine for opioid-naive cancer pain

When suitable, start a total of 20 to 30 mg oral morphine over 24 hours, for example 5 mg immediate release every 4 hours or 10 to 15 mg modified release every 12 hours, plus 5 mg immediate-release rescue.

Start lower in frailty and seek specialist advice in renal or hepatic impairment; monitor sedation and breathing, avoid unsafe sedative combinations and co-prescribe regular laxative with driving and secure-storage advice.

Provides continuous strong opioid when pain is stable but oral treatment is unsuitable because of swallowing, adherence or intolerable morphine-related effects.

Transdermal fentanyl

Use the product-specific patch strength derived from the current stable 24-hour oral-morphine equivalent, commonly changed every 72 hours, with specialist verification and an immediate-release rescue opioid.

Do not start for rapidly changing pain or in an opioid-naive patient; fever and heat can increase absorption, cachexia may make exposure unpredictable and drug persists after patch removal.

Prevents opioid-induced slow transit and faecal impaction, for which tolerance does not reliably develop during continuing treatment.

Regular constipation prophylaxis

Start a stimulant such as senna 15 mg at night plus an osmotic laxative such as macrogol one sachet daily when regular strong opioid begins, titrating to comfortable stool and local formulary guidance.

Exclude obstruction before aggressive oral laxative, review hydration and electrolytes and use a rectal examination and rectal regimen when impaction is suspected rather than repeatedly adding oral medicine.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Loss of function and sleep

Undertreated pain drives immobility, falls, pressure injury, insomnia, appetite loss, delirium and inability to attend or tolerate anticancer treatment.

Opioid-induced bowel dysfunction

Reduced intestinal propulsion causes constipation, nausea, reflux, faecal impaction and occasionally obstruction unless prophylaxis and bowel monitoring begin with regular strong opioid.

Sedation and respiratory depression

Rapid titration, renal accumulation, interacting sedatives and acute illness can depress consciousness and ventilation, particularly in opioid-naive, frail or sleep-disordered patients.

Neurotoxicity and endocrine effects

High exposure can cause hallucination, delirium, myoclonus and hyperalgesia, while prolonged treatment may impair gonadal hormones and contribute to fatigue and osteoporosis.

Dependence, diversion and stigma

Physical dependence is expected with regular therapy, while misuse and diversion require proportionate safeguards that do not deny legitimate cancer-pain relief.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Review soon after initiation or dose change and record pain at rest and movement, sleep, function, total rescue use and whether the agreed goal is being achieved.
Check alertness, respiratory rate, oxygenation when indicated, hallucination, myoclonus, falls, driving and interacting benzodiazepine, alcohol, antihistamine and gabapentinoid exposure.
Ask directly about stool frequency, consistency, straining, abdominal pain and nausea and escalate to impaction or obstruction assessment when the pattern changes.
Repeat renal and liver function when illness, dehydration, cachexia or treatment changes can alter opioid clearance; do not wait for profound toxicity.
Reconcile every formulation and patch at transitions of care and write total daily opioid, rescue, last patch change and conversion basis in the handover.
After radiotherapy, surgery, block or systemic response, reduce regular opioid gradually while preserving rescue and watching pain recurrence and withdrawal.
Review mood, fear, family strain, sleep, work and caregiver understanding and involve palliative, psychological, social and spiritual support according to patient priorities.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Movement pain is anatomical information

A patient who is comfortable still but has severe femoral pain on standing may need stabilisation, not merely a higher background opioid.

Rescue use is a monitoring signal

Repeated effective doses suggest inadequate background control, while repeated ineffective doses suggest a wrong mechanism, emergency or absorption problem.

Constipation prevention starts on day one

Waiting for impaction creates pain, nausea, delirium and apparent opioid intolerance that could have been prevented with a bowel plan.

Patch pharmacology is slow

Fentanyl concentration rises and falls over many hours, so rapid stacking, external heat or premature replacement can produce delayed toxicity.

Renal failure changes the molecule

Morphine metabolites accumulate when filtration falls, making confusion and myoclonus a reason to rotate and treat the renal precipitant.

Dependence is not addiction

Expected withdrawal after abrupt stopping differs from compulsive harmful use; clear language reduces stigma while safe storage and review remain necessary.

11Common pitfallsFrequent interpretation and management errors.

01
Increasing opioid before examining a new pain pattern for cord compression, fracture, obstruction or infection.
02
Recording a pain score without mechanism, movement effect, rescue response or functional goal.
03
Starting regular strong opioid without immediate-release rescue and constipation prophylaxis.
04
Using a fentanyl patch for rapidly escalating pain in an opioid-naive patient.
05
Applying a conversion ratio without totalling rescue use or reducing for incomplete cross-tolerance.
06
Using morphine unchanged through severe renal decline and interpreting myoclonus as anxiety.
07
Layering benzodiazepine, gabapentinoid and opioid without reviewing respiratory and falls risk.
08
Giving a full naloxone bolus to an opioid-dependent patient when careful titration could restore ventilation without a pain and withdrawal crisis.
09
Treating psychosocial distress instead of physical pain or ignoring it after physical prescribing.
10
Continuing the same opioid dose after successful local treatment without deprescribing review.