7th January 2024

Approach to management of pain

The World Health Organisation’s Method for Relief of Cancer pain underpins the use of analgesia in cancer pain. Although almost 40 years old, there are several principles within this document which are still relevant to this day.

• “By the clock”: treatment of chronic pain requires regular analgesia as a preventative measure, not just on an ‘as required’ basis.
• “By the individual”: acknowledging that different patients will need different analgesic doses, and ongoing assessment and careful dose titration is important to achieve this.
• “By the mouth”: injections can be painful, and syringe drivers and other medical devices can be burdensome. The oral route is, therefore, preferred.
• “With attention to detail”: patients should be monitored for side effects of analgesia, which should be treated.
• “By the ladder”: the same document created the well-known World Health Organisation analgesic ladder, outlining the stepwise approach to analgesia.

Source: Adapted from World Health Organisation. Cancer pain relief 1986. Geneva [Cited 2/3/2022]. Available at: https://apps.who.int/iris/bitstream/handle/10665/43944/9241561009_eng.pdf

Paracetamol

This is a non-opioid analgesic available over the counter in the UK and traditionally used as step 1 of the analgesic ladder. The recommended dose is 1g four times a day, but this is reduced to 500mg in patients with a weight of <50kg, poor nutritional status, or hepatic impairment. It mainly acts within the CNS and has some weak impact on prostaglandin synthesis. Combining Paracetamol and NSAIDs has been shown to improve analgesia. This suggests differing modes of action; hence, Paracetamol is not considered an NSAID.

Paracetamol, in combination with opioids, has been shown to improve overall pain control and reduce opioid requirements (opioid-sparing). It is, therefore, appropriate to continue Paracetamol alongside strong opioids even at step 3 of the WHO analgesic ladder.

NSAIDs

NSAIDs’ anti-inflammatory effect is through Cyclo-Oxygenase (COX) inhibition, reducing prostaglandin synthesis. This reduces inflammation-induced nociceptive pain. This is particularly effective in visceral and somatic nociceptive pain.

Ibuprofen is available over the counter with a typical starting dose of 400mg three times daily. Naproxen is a commonly used NSAID with a starting dose of 500mg twice daily.

Proton pump inhibitors should be prescribed alongside NSAIDs due to the risk of peptic ulcer disease and gastropathy. This is less likely at lower doses. NSAIDs should be used with caution in renal impairment, thrombocytopenia, and cardiac dysfunction.

COX-2 selectivity

COX-2 is associated with painful inflammation, whereas COX-1 is more physiological. There are more than 20 NSAIDs grouped based on the selectivity of COX-1 or 2 inhibition. Ibuprofen and Naproxen are non-selective, whereas Diclofenac is a preferential COX-2 inhibitor.

Celecoxib is a more selective COX-2 inhibitor, which may be utilised in bone pain or soft tissue disease. The starting dose is 100mg twice daily, which can be uptitrated to 200mg twice daily. Celecoxib has a lower risk of GI side effects and is the Palliative Care Formulary’s NSAID of choice.

Codeine

Codeine is the most typically used weak opioid at step 2 of the WHO analgesic ladder. Other options include Dihydrocodeine and Tramadol.

The body must first metabolise Codeine to Morphine for analgesic effect. Opioid conversions will be discussed later, but Codeine is 1/10 as strong as Morphine. There is little evidence of its use in place of strong opioids; studies show there is better pain control quicker from low-dose morphine than codeine. Where strong opioids are readily available, it is common for step 2 to be bypassed.

If step 2 is utilised, the non-opioid analgesic in step 1 is not stopped. If a weak opioid is not beneficial, uptitration is by stopping the weak opioid and switching to a strong opioid and step 3 of the analgesic ladder.

References

• Twycross R, Wilcock A. Introducing Palliative Care 5ᵗʰ edition 2016. 87-93
• World Health Organisation. Cancer pain relief 1986. Geneva [Cited 20/2/2022]. Available at: https://apps.who.int/iris/bitstream/handle/10665/43944/9241561009_eng.pdf
• Scottish Palliative Care Guidelines [Internet]. 2020 [Cited 20/2/2022]. Available at: https://www.palliativecareguidelines.scot.nhs.uk/
• UpToDate [Internet]. Uptodate.com 2021 [Cited 20/2/2022]. Available from: https://www.uptodate.com/contents/assessment-of-cancer-pain?search=cancer%20pain%20management&source=search_result&selectedTitle=8~150&usage_type=default&display_rank=8#H3
• UpToDate [Internet]. Uptodate.com 2021 [Cited 20/2/2022]. Available from: https://www.uptodate.com/contents/pharmacologic-management-of-chronic-non-cancer-pain-in-adults?search=non%20opioid%20pain%20management&source=search_result&selectedTitle=2~150&usage_type=default&display_rank=2#H3009310947
• Twycross R, Wilcock A, Howard P. Palliative Care Formulary 6th edition 2017. 295-352
• Greater Manchester and Eastern Cheshire Strategic Clinical Networks. Palliative Care Pain & Symptom Control Guidelines for Adults 2019 [Internet] [Cited 20/2/2022]. Available at: https://gmmmg.nhs.uk/guidance/clinical-guidance-and-pathways/