WHO analgesic approach and multimodal analgesia

01Purpose and principlesWhat the treatment does and how it fits into care.

The three-step WHO framework remains a useful organising concept for cancer pain but is not a compulsory staircase. Step one uses non-opioid analgesia with or without an adjuvant. Step two traditionally adds a weak opioid such as codeine. Step three uses a strong opioid for moderate-to-severe pain. At every step, assess mechanism, treat reversible pathology, provide rescue for predictable flares and monitor function and toxicity.

Weak opioids have limitations. Codeine depends on CYP2D6 conversion to morphine, giving variable analgesia and toxicity, and its metabolites accumulate in renal impairment. Combining it with paracetamol creates a ceiling imposed by the non-opioid component. In severe progressive pain, a lower carefully titrated dose of strong opioid can be more controllable than maximising a weak opioid, provided the patient receives education, constipation prophylaxis and close review.

Multimodal analgesia combines interventions with different targets so that no single drug carries the entire burden. Examples include stabilisation and radiotherapy for painful metastasis, antispasmodic treatment for colic, neuropathic adjuvant for nerve injury, physiotherapy and equipment for mechanical pain, and psychological support for fear-driven avoidance. Complementary measures should be evaluated for safety and should not displace effective emergency or disease-directed treatment.

Regular treatment is appropriate when pain persists continuously; as-needed-only prescribing invites recurrent peaks and delayed relief. Conversely, an automatic regular regimen can be harmful when pain is episodic, clearance is changing or the cause has resolved. Match formulation and interval to the temporal pattern. Use the oral route when reliable, but consider subcutaneous, transdermal or other routes when swallowing, absorption, vomiting or adherence makes oral treatment unsafe.

Review non-opioids rather than allowing them to continue indefinitely. Paracetamol may add modest benefit but carries dose-related liver risk, particularly with low body weight, malnutrition, alcohol excess or liver disease. NSAIDs may help inflammatory and bone pain but can cause bleeding, renal injury, fluid retention and cardiovascular harm. Agree a short therapeutic trial with a target and stop when benefit is absent.

The pain plan should be understandable outside the specialist clinic. List the indication for every medicine, scheduled and rescue doses, maximum and minimum interval, constipation and nausea plans, interaction warnings, storage, driving advice and whom to contact. Reconcile the regimen after hospital transfer because brand, formulation and route changes are common sources of duplication.

Key points

The WHO ladder was developed for cancer pain: non-opioid at step one, opioid for mild-to-moderate pain at step two and strong opioid at step three, with adjuvants throughout.
Use the ladder flexibly rather than forcing slow progression; severe cancer pain may require a carefully started strong opioid without a prolonged weak-opioid trial.
Core principles are an appropriate route, regular treatment for continuous pain, rescue for breakthrough pain, individual titration and attention to detail.
First-line multimodal planning treats the cause and mechanism: radiotherapy, surgery, anti-inflammatory treatment, nerve intervention, rehabilitation and psychological support may reduce drug burden.
Paracetamol or an NSAID can help selected nociceptive pain, but continue only when repeated review shows benefit greater than hepatic, renal, gastrointestinal or cardiovascular risk.
Avoid combining two strong opioids routinely or mixing immediate-release products without a single documented total-dose plan.
Adjuvant analgesics are selected for neuropathic, inflammatory, bone, spasm or pressure mechanisms and need their own titration and adverse-effect monitoring.
There is no universal gold-standard drug sequence: the benchmark is mechanism-linked analgesia that improves a patient-defined outcome with tolerable harm.
Chronic primary pain is not managed by importing the cancer ladder; NICE advises against initiating several dependence-forming analgesics for that condition.

02Indications, selection and cautionsWho may benefit, who needs urgent treatment and important alternatives.

Step-one candidate

Mild nociceptive pain without emergency pathology may respond to paracetamol, a short NSAID trial or local measures when contraindications are addressed.

Strong-opioid need

Persistent moderate-to-severe cancer or advanced-disease pain that impairs function despite appropriate measures may justify direct step-three titration.

Neuropathic component

Burning, electric pain, allodynia and sensory deficit signals need for a neuropathic pathway rather than opioid escalation alone.

Inflammatory or bone mechanism

Movement tenderness, night pain, swelling or metastatic lesion may respond to anti-inflammatory, stabilising or radiotherapy treatment alongside analgesia.

Regimen burden

Confusion, missed doses, duplicate combination products or caregiver calculation errors indicate that simplification may improve both safety and analgesia.

Multimodal failureRed flag

Escalating toxicity without functional gain suggests the formulation or target is wrong and warrants specialist reassessment.

Red flags requiring action

New neurological deficit, pathological fracture features or visceral obstruction requires urgent cause-directed treatment rather than analgesic escalation alone.
Respiratory slowing, marked sedation, hallucinations or myoclonus during opioid treatment requires toxicity assessment before the next dose.
NSAID use with acute kidney injury, gastrointestinal bleeding, severe heart failure or anticoagulation may create disproportionate harm.
Combination products can conceal duplicate paracetamol or opioid exposure and cause accidental overdose.
Gabapentinoids, benzodiazepines, alcohol and opioids together increase sedation and respiratory risk, especially with frailty or sleep-disordered breathing.
Persistent severe pain despite rational measures needs specialist review for mechanism, procedure, radiotherapy, opioid rotation or psychological complexity.

03Assessment before treatmentTests and checks that guide safe selection.

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 mechanism and severity formulationFirst stepFirst line
Why
Identify nociceptive, neuropathic, inflammatory, mechanical and psychosocial contributors and the need for urgent disease treatment.
Interpretation and limitations
Choose modalities for the dominant mechanisms; severity can justify a strong opioid but never replaces diagnosis or safety assessment.
02
Medicine and contraindication review
Why
Check all analgesics, combinations, rescue use, allergies, interactions, organ function, bleeding risk, sedatives and previous response.
Interpretation and limitations
Remove duplicate or ineffective treatment and select the safest viable component before adding another rung or adjuvant.
03
Functional goal and baseline score
Why
Agree a concrete outcome such as sleep, walking, cough, wound care or ability to receive radiotherapy and record current performance.
Interpretation and limitations
Continue or escalate a modality only when its improvement justifies adverse effects and practical burden.
04
Cause-directed assessment
Why
Determine whether radiotherapy, fixation, nerve block, anti-inflammatory treatment, drainage, rehabilitation or psychological therapy may address the source.
Interpretation and limitations
A disease or procedural modality can be analgesic first-line even while drug treatment provides interim relief.
05
Renal and hepatic function
Why
Identify altered clearance or contraindications for opioids, NSAIDs, paracetamol and adjuvant medicines.
Interpretation and limitations
Worsening clearance requires dose, interval or drug change with BNF, local formulary and pharmacy or specialist support.
06
Structured early review
Why
Reassess benefit, rescue frequency, cognition, bowel function, nausea, falls and ability to follow the regimen after initiation.
Interpretation and limitations
This response review is the practical gold standard for deciding whether to maintain, titrate, rotate, simplify or stop a component.

04Treatment approachPreparation, options, escalation and aftercare.

01Analgesic selectionChoose intensity and modality by mechanismFirst stepPain requires a new or revised treatment plan after emergency causes have been addressed.

1Formulate pain mechanisms and severity, define a functional goal and identify disease-directed, physical and psychosocial treatments that can alter the cause.
2Select non-opioid, opioid and adjuvant components with organ function and interactions considered, moving directly to carefully titrated strong opioid when severe cancer pain warrants it.
3Write scheduled and rescue instructions, bowel and nausea support, safety advice and an early review date, then stop components that do not add measurable benefit.

02Non-opioid trialUse a goal and stop ruleParacetamol or an NSAID may add benefit for nociceptive, inflammatory or bone pain.

1Check liver, renal, gastrointestinal, cardiovascular, bleeding and interaction risks and reconcile hidden combination-product exposure.
2Start the lowest appropriate formulary dose for a defined short interval with any indicated gastroprotection and a patient-selected outcome.
3Review benefit and toxicity promptly, continue only if gain is meaningful and stop or reduce when risk rises or the target is not achieved.

03Persistent painEscalate across modalitiesEscalationPain remains unacceptable despite a rational ladder-based regimen or dose-limiting adverse effects appear.

1Reassess diagnosis, temporal pattern, adherence, toxicity, organ function and neuropathic or mechanical mechanisms before increasing opioid.
2Seek oncology, palliative, pain, radiotherapy, orthopaedic, rehabilitation or psychological input for the identified treatment gap.
3Agree one coordinated plan, avoid competing prescriptions and evaluate function, rescue need and harm within a timeframe appropriate to the intervention.

04Care transitionReconcile a multimodal regimenThe patient moves between hospital, hospice, care home and community or the oral route changes.

1Verify exact generic drugs, formulations, strengths, schedules, rescue instructions and last doses against prescriptions, administration records and patient supply.
2Resolve duplicate opioids, combination products and route conversions with the prescriber and pharmacy before administration.
3Provide an updated plain-language schedule, controlled-drug storage and disposal advice and a contact for pain or toxicity deterioration.

05Regimens, contraindications and interactionsTreatment details and the circumstances that modify them.

May reduce mild nociceptive pain or add opioid-sparing benefit during an individual therapeutic trial.

Paracetamol for selected nociceptive pain

For an adult at least 50 kg without relevant risk, 500 mg to 1 g orally every 4 to 6 hours when required, maximum 4 g in 24 hours; use a lower maximum when low weight, frailty, malnutrition, alcohol excess or liver disease requires it.

Reconcile combination products and all routes; follow the BNF and local low-body-weight or liver-risk policy and stop if no worthwhile benefit.

Can help inflammatory, soft-tissue and bone pain and may reduce opioid requirement in selected patients.

Ibuprofen as a short anti-inflammatory trial

When appropriate, use 200 to 400 mg orally up to three times daily with or after food for the shortest necessary course, following the BNF and local gastroprotection policy.

Avoid or seek specialist advice with renal injury, peptic ulcer or bleeding, anticoagulation, severe heart failure, uncontrolled hypertension, NSAID-sensitive asthma or high frailty.

Offers opioid analgesia for some moderate pain but may be bypassed in severe cancer pain in favour of controlled strong-opioid titration.

Codeine at the traditional second step

Use 30 to 60 mg orally every 4 hours when an individual second-step trial is appropriate, not exceeding 240 mg in 24 hours and accounting for any combination product.

Variable CYP2D6 metabolism makes effect unpredictable; constipation, sedation and renal accumulation occur, and it must not be combined casually with another opioid.

Reference first-line strong opioid for persistent moderate-to-severe pain when the oral route and clearance are suitable.

Oral morphine at the strong-opioid step

For advanced progressive disease requiring a strong opioid and without significant renal or hepatic impairment, NICE describes 20 to 30 mg total oral sustained-release morphine daily plus 5 mg immediate-release morphine for rescue during initial titration; individualise lower in frailty.

Prescribe a laxative, counsel about sedation and driving, review frequently and obtain specialist or pharmacy advice for organ impairment, conversion, toxicity or rapidly changing pain.

06Complications, monitoring and follow-upAdverse effects, response and longer-term review.

Review the patient-defined functional target as well as pain intensity after each new modality or titration.
Track scheduled adherence, rescue frequency, treatment onset and duration to distinguish underdosing from mismatched episode kinetics.
Monitor bowel function, nausea, alertness, hallucinations, myoclonus, respiratory rate, falls and driving risk during opioid treatment.
Recheck renal, hepatic, gastrointestinal and cardiovascular risk when continuing non-opioids or when acute illness changes clearance.
Stop an adjuvant or non-opioid that provides no measurable benefit after an adequate agreed trial rather than accumulating medicines.
Confirm one clinician or team coordinates controlled-drug changes and that every setting holds the same current schedule.

07Special situationsVariants, exceptions and circumstances that change the usual approach.

The ladder is not a delay rule

Severe progressive cancer pain can justify carefully supervised strong-opioid initiation without exhausting a weak opioid first.

By mouth is conditional

The oral route is convenient only when swallowing, absorption, adherence and onset match the clinical need.

By the clock has exceptions

Continuous pain benefits from regular treatment, whereas episodic pain and changing clearance require a more individual schedule.

Disease treatment is analgesia

Radiotherapy, stabilisation, drainage or anti-inflammatory treatment may relieve more pain with less sedation than opioid escalation.

Combination products create ceilings

Paracetamol content may limit codeine escalation and hidden duplication can turn a familiar tablet into an overdose risk.

Multimodal should remain rational

Adding medicines with overlapping sedation but no distinct target is polypharmacy, not effective multimodal analgesia.

08Common pitfallsFrequent interpretation and management errors.

01
Making every patient complete each WHO step despite severe pain.
02
Using the cancer ladder to justify long-term opioids for chronic primary pain.
03
Continuing paracetamol or NSAIDs indefinitely without evidence of added benefit.
04
Missing duplicate paracetamol in compound opioid products.
05
Combining two regular strong opioids without a documented specialist plan.
06
Adding sedating adjuvants without renal, falls and interaction review.
07
Escalating tablets while delaying radiotherapy, fixation, drainage or rehabilitation.
08
Prescribing regular analgesia without a safe rescue and constipation plan.
09
Changing route or formulation during transfer without medicine reconciliation.
10
Measuring success only by score and overlooking lost alertness or mobility.