Cancer Pain and the Analgesic Ladder

Introduction

Pain is what patients fear most about cancer, and it is the symptom in which good and bad practice diverge most sharply. Around half of all patients with cancer experience pain, rising to two-thirds in advanced disease, and although it can be controlled in the great majority, surveys consistently find that a third are undertreated.^1,5

The barriers are rarely pharmacological. They are the clinician's fear of prescribing opioids, the patient's fear of taking them, incomplete assessment that treats "pain" as one thing when the patient has three different pains with three different mechanisms, and failure to address the distress that amplifies all of them.

Total pain, the concept introduced by Cicely Saunders, is the organising idea. A patient's experience of pain is the sum of the nociceptive input and their fear, isolation, loss of role, financial worry and spiritual distress. This is not a soft observation: it explains why a patient whose morphine dose has been escalated three times without benefit may respond to a conversation about what is frightening them, and why the multidisciplinary team matters.

Assessment

The commonest reason for failed pain control is inadequate assessment. Patients with advanced cancer typically have more than one pain, often of different types, and each needs to be characterised separately - so ask "tell me about each of your pains" rather than "how bad is your pain".

Use SOCRATES for each: Site, Onset, Character, Radiation, Associated symptoms, Timing, Exacerbating and relieving factors, Severity. Then add the questions specific to cancer pain:

• Background versus breakthrough - is the pain constant with intermittent flares, and what brings the flares on?
• Incident pain - pain triggered predictably by movement, dressing changes or coughing, which needs a different strategy from background pain
• Impact - on sleep, mobility, appetite, mood and the ability to do what matters to them. A numerical score is far less useful than knowing that the pain stops them sleeping or getting to the toilet.
• What they are already taking, whether they actually take it, at what dose and how often, and what happened when they did
• Beliefs and fears - many patients ration their analgesia because they fear addiction, believe morphine is "the last resort" or a sign they are dying, or want to save it for when the pain is worse. These need to be asked about directly and addressed.
• Psychological, social and spiritual factors - anxiety, depression, isolation, unfinished business

Classifying the pain

The WHO analgesic ladder

The WHO ladder remains the framework for cancer pain, alongside its five accompanying principles: by mouth (use the oral route wherever possible), by the clock (regular dosing rather than as-required, so pain does not have to return before the next dose), by the ladder, for the individual (there is no ceiling dose for a strong opioid - the right dose is the one that controls the pain), and with attention to detail.¹

Prescribing strong opioids

Starting morphine

NICE recommends offering oral immediate-release or modified-release morphine as first-line strong opioid, with immediate-release morphine for breakthrough pain in all patients.²

1. Start with either immediate-release morphine 5 mg every 4 hours, or modified-release morphine 10 to 15 mg twice daily - typically 20 to 30 mg total in 24 hours in an opioid-naive adult
2. Reduce the starting dose to 2.5 mg four-hourly in frail or elderly patients, in renal impairment, and in anyone at risk of toxicity
3. Prescribe a breakthrough dose of immediate-release morphine equal to one-sixth of the total 24-hour dose, available as often as required (commonly hourly, with review if used repeatedly)
4. Always co-prescribe a laxative - a stimulant such as senna with a softener, or a combined preparation
5. Prescribe an antiemetic as required for the first week - metoclopramide or haloperidol
6. Review within 24 to 48 hours. Add up the breakthrough doses used in the previous 24 hours, add that to the regular dose, and redistribute. Increase in increments of no more than 30 to 50%.
7. Convert to a modified-release preparation once the requirement is stable, keeping the breakthrough dose at one-sixth of the new total

Opioid conversion

Conversion factors are approximate, vary slightly between sources, and must always be checked against local guidance and the BNF before prescribing.^4,6 When switching opioid because of toxicity or poor response, it is standard practice to reduce the calculated equivalent dose by 25 to 50% because cross-tolerance is incomplete.

Renal and hepatic impairment

Morphine is metabolised to morphine-6-glucuronide and morphine-3-glucuronide, both renally excreted and both accumulating in renal impairment - the first causing sedation and respiratory depression, the second causing agitation, myoclonus and hyperalgesia. This is the single commonest cause of opioid toxicity on a general ward.

• eGFR above 30 - morphine can be used with a reduced dose and extended interval, with close monitoring; oxycodone is often preferred
• eGFR below 30, or dialysis - avoid morphine. Use alfentanil (short-acting, ideal in a syringe driver), fentanyl or buprenorphine, none of which have active renally cleared metabolites.
• Hepatic impairment - reduce doses and extend intervals for all opioids; avoid codeine and tramadol, which require hepatic activation, and avoid paracetamol at full dose in severe impairment

Opioid side effects and toxicity

Two other conversations belong here. Addiction is very rare when opioids are used for cancer pain, and patients who fear it should be reassured while distinguishing tolerance and physical dependence, which are normal physiological adaptations, from addiction, which is a behavioural disorder. Driving is permitted on stable opioid doses provided the patient is not impaired, but they must not drive when starting or increasing a dose, and should be told that they are legally responsible for judging their fitness to drive.⁷

Adjuvant analgesics and non-drug measures

Adjuvants are drugs whose primary indication is not analgesia but which relieve specific pain mechanisms. Matching the adjuvant to the mechanism is where most of the improvement in difficult cancer pain comes from.

Interventional options

• Coeliac plexus block - highly effective for the visceral pain of pancreatic and upper abdominal cancer, and worth considering early rather than after opioid escalation has failed
• Intrathecal or epidural analgesia with an implanted pump, for pain refractory to systemic treatment or where systemic side effects are intolerable
• Nerve blocks and neurolytic procedures, including intercostal and paravertebral blocks
• Vertebroplasty or kyphoplasty for painful vertebral collapse
• Percutaneous cordotomy, occasionally used for unilateral pain such as mesothelioma

Non-pharmacological measures

These are not an afterthought. Physiotherapy, positioning, aids and adaptations, TENS, heat and cold, acupuncture, and relaxation and mindfulness techniques all have a place. So does treating anxiety and depression, addressing practical and financial worries with a social worker, and offering spiritual support - all of which change how much the physical pain hurts.³ The specialist palliative care team, clinical nurse specialist, physiotherapist, occupational therapist and chaplaincy are the people who deliver most of this.

Red flags

Outcomes

Cancer pain can be adequately controlled in around 80 to 90% of patients using the WHO framework with careful assessment and appropriate adjuvants.¹ The residual group - typically those with neuropathic pain from plexus infiltration, severe incident pain from bone disease, or a large component of psychological distress - are the ones who benefit from specialist palliative care and interventional techniques, and they should be referred early rather than after a series of failed dose increases.

Two practical habits do most of the work. The first is reviewing: an opioid prescription without a review date is not a plan, and the dose that was right last week may be toxic this week if renal function has changed. The second is anticipating: prescribing the breakthrough dose, the laxative and the antiemetic at the same time as the opioid, and making sure a patient going home has anticipatory medicines and a number to ring.

Finally, it is worth saying plainly what the evidence shows: properly titrated opioids used for pain do not shorten life. The fear that giving adequate analgesia to a dying patient hastens death is both widespread and mistaken, and it causes real suffering. Undertreated pain, by contrast, is measurably harmful - and it is the failure examiners are testing you to avoid.